One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
A cell line derived from cultured tumor cells.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
Established cell cultures that have the potential to propagate indefinitely.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
Glycoproteins found on the membrane or surface of cells.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Elements of limited time intervals, contributing to particular results or situations.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Transport proteins that carry specific substances in the blood or across cell membranes.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
The action of a drug in promoting or enhancing the effectiveness of another drug.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Proteins prepared by recombinant DNA technology.
The process by which chemical compounds provide protection to cells against harmful agents.
The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Peptides composed of between two and twelve amino acids.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Tumors or cancer of the COLON.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.
Tumors or cancer of the PROSTATE.
Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455)
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
Tumors or cancer of the human BREAST.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A group of phenyl benzopyrans named for having structures like FLAVONES.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
Compounds that inhibit cell production of DNA or RNA.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).
Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION).
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Inorganic or organic compounds that contain arsenic.

Inducible NO synthase: role in cellular signalling. (1/71063)

The discovery of endothelium-derived relaxing factor and its identification as nitric oxide (NO) was one of the most exciting discoveries of biomedical research in the 1980s. Besides its potent vasodilatory effects, NO was found under certain circumstances to be responsible for the killing of microorganisms and tumour cells by activated macrophages and to act as a novel, unconventional type of neurotransmitter. In 1992, Science picked NO as the 'Molecule of the Year', and over the past years NO has become established as a universal intercellular messenger that acutely affects important signalling pathways and, on a more long-term scale, modulates gene expression in target cells. These actions will form the focus of the present review.  (+info)

VEGF is required for growth and survival in neonatal mice. (2/71063)

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.  (+info)

A Drosophila doublesex-related gene, terra, is involved in somitogenesis in vertebrates. (3/71063)

The Drosophila doublesex (dsx) gene encodes a transcription factor that mediates sex determination. We describe the characterization of a novel zebrafish zinc-finger gene, terra, which contains a DNA binding domain similar to that of the Drosophila dsx gene. However, unlike dsx, terra is transiently expressed in the presomitic mesoderm and newly formed somites. Expression of terra in presomitic mesoderm is restricted to cells that lack expression of MyoD. In vivo, terra expression is reduced by hedgehog but enhanced by BMP signals. Overexpression of terra induces rapid apoptosis both in vitro and in vivo, suggesting that a tight regulation of terra expression is required during embryogenesis. Terra has both human and mouse homologs and is specifically expressed in mouse somites. Taken together, our findings suggest that terra is a highly conserved protein that plays specific roles in early somitogenesis of vertebrates.  (+info)

Alzheimer's disease: clues from flies and worms. (4/71063)

Presenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid beta peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked.  (+info)

Cell-mediated immunity: dealing a direct blow to pathogens. (5/71063)

Cytotoxic T lymphocytes are essential for defence against viral infections. Recent data demonstrating direct killing of intracellular bacteria by granulysin, a protein released from the granules of cytotoxic T lymphocytes, emphasize the contribution of these lymphocytes to the control of tuberculosis.  (+info)

JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. (6/71063)

BACKGROUND: The Jun N-terminal kinase (JNK) signaling pathway has been implicated in cell proliferation and apoptosis, but its function seems to depend on the cell type and inducing signal. In T cells, JNK has been implicated in both antigen-induced activation and apoptosis. RESULTS: We generated mice lacking the JNK2 isozymes. The mutant mice were healthy and fertile but defective in peripheral T-cell activation induced by antibody to the CD3 component of the T-cell receptor (TCR) complex - proliferation and production of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) were reduced. The proliferation defect was restored by exogenous IL-2. B-cell activation was normal in the absence of JNK2. Activation-induced peripheral T-cell apoptosis was comparable between mutant and wild-type mice, but immature (CD4(+) CD8(+)) thymocytes lacking JNK2 were resistant to apoptosis induced by administration of anti-CD3 antibody in vivo. The lack of JNK2 also resulted in partial resistance of thymocytes to anti-CD3 antibody in vitro, but had little or no effect on apoptosis induced by anti-Fas antibody, dexamethasone or ultraviolet-C (UVC) radiation. CONCLUSIONS: JNK2 is essential for efficient activation of peripheral T cells but not B cells. Peripheral T-cell activation is probably required indirectly for induction of thymocyte apoptosis resulting from administration of anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and stimulus-dependent manner, being required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for apoptosis induced by anti-Fas antibody, UVC or dexamethasone. JNK2 is not required for activation-induced cell death of mature T cells.  (+info)

Bcl-2 regulates amplification of caspase activation by cytochrome c. (7/71063)

Caspases, a family of specific proteases, have central roles in apoptosis [1]. Caspase activation in response to diverse apoptotic stimuli involves the relocalisation of cytochrome c from mitochondria to the cytoplasm where it stimulates the proteolytic processing of caspase precursors. Cytochrome c release is controlled by members of the Bcl-2 family of apoptosis regulators [2] [3]. The anti-apoptotic members Bcl-2 and Bcl-xL may also control caspase activation independently of cytochrome c relocalisation or may inhibit a positive feedback mechanism [4] [5] [6] [7]. Here, we investigate the role of Bcl-2 family proteins in the regulation of caspase activation using a model cell-free system. We found that Bcl-2 and Bcl-xL set a threshold in the amount of cytochrome c required to activate caspases, even in soluble extracts lacking mitochondria. Addition of dATP (which stimulates the procaspase-processing factor Apaf-1 [8] [9]) overcame inhibition of caspase activation by Bcl-2, but did not prevent the control of cytochrome c release from mitochondria by Bcl-2. Cytochrome c release was accelerated by active caspase-3 and this positive feedback was negatively regulated by Bcl-2. These results provide evidence for a mechanism to amplify caspase activation that is suppressed at several distinct steps by Bcl-2, even after cytochrome c is released from mitochondria.  (+info)

Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-kappaB. (8/71063)

To maintain the integrity of the vascular barrier, endothelial cells (EC) are resistant to cell death. The molecular basis of this resistance may be explained by the function of antiapoptotic genes such as bcl family members. Overexpression of Bcl-2 or Bcl-XL protects EC from tumor necrosis factor (TNF)-mediated apoptosis. In addition, Bcl-2 or Bcl-XL inhibits activation of NF-kappaB and thus upregulation of proinflammatory genes. Bcl-2-mediated inhibition of NF-kappaB in EC occurs upstream of IkappaBalpha degradation without affecting p65-mediated transactivation. Overexpression of bcl genes in EC does not affect other transcription factors. Using deletion mutants of Bcl-2, the NF-kappaB inhibitory function of Bcl-2 was mapped to bcl homology domains BH2 and BH4, whereas all BH domains were required for the antiapoptotic function. These data suggest that Bcl-2 and Bcl-XL belong to a cytoprotective response that counteracts proapoptotic and proinflammatory insults and restores the physiological anti-inflammatory phenotype to the EC. By inhibiting NF-kappaB without sensitizing the cells (as with IkappaBalpha) to TNF-mediated apoptosis, Bcl-2 and Bcl-XL are prime candidates for genetic engineering of EC in pathological conditions where EC loss and unfettered activation are undesirable.  (+info)

METHODS: The cytotoxic effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 50% inhibitory concentration (IC50) value was determined. The self-renewal and proliferating potential of A549 cells after treatment with deoxyelephantopin were examined by colony formation assay. Cellular morphology of deoxyelephantopin-treated cells was observed using phase-contrast microscopy. The induction of apoptosis was evaluated using acridine orange and ethidium bromide staining, Hoechst 33342 staining, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) assay, DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate staining by flow cytometry. Activation of caspases was detected using fluorogenic substrate specific to caspases 2, 3, 8 and 9 and flow cytometric analysis. The total cellular DNA content and expression of cleaved poly (ADP-ribose) polymerase was ...
Read independent reviews on CardioTACS™ In Situ Apoptosis Detection Kits from AMS Biotechnology (Archived Products) on SelectScience
Anti-apoptotic action of polyphenols derived from red wine and green tea against beta-amyloid in hippocampal cells Author: Stéphane Bastianetto and Slavica Krantic and Rémi Quirion Background: It has been suggested that accumulation of amyloid-beta (Aß) peptides into senile plaques plays a pivotal role in neuronal cell
BioAssay record AID 541028 submitted by ChEMBL: Induction of apoptosis in bovine BL3 cells assessed as early apoptotic cells after 24 hrs by annexin V/propidium iodide staining-based FACS analysis.
During apoptosis, phosphatidylserine (PS) is translocated from the cytoplasmic face of the plasma membrane to the cell surface. Annexin V has a strong, Ca2+-dependent affinity for PS and therefore is used as a probe for detecting apoptosis., Annexin V-FITC Apoptosis Detection Reagent, GTX14082, Applications: FACS; Flow cytometry/FACS; CrossReactivity:
The Annexin V-Biotin Apoptosis Detection Kit is based on the observation that soon after initiating apoptosis, most cell types translocate the membrane phospholipid phosphatidylserine (PS) from the inner face of the plasma membrane to the cell surface. Once on the cell surface, PS can easily bind to Biotin-conjugated Annexin V, a protein that has a strong natural affinity for PS. Annexin V-Biotin can be detected in conjunction with conventional dye-staining using any streptavidine- or avidin-dye reagents, such as (strept)avidine-fluorescein, -peroxidase, -alkaline phosphatase (AP), and -β-gal, etc. |p>‧ Detection method- Flow cytometry (Ex = 488 nm; Em = 530 nm) using and fluorescence microscopy |br>‧ Sample type- Living cells (suspension and adherant)|br>‧ Species reactivity- Mammalian |br>‧ Applications- Detect early/middle stages of apoptosis; differentiate apoptosis from necrosis.|p>|b>Features and Benefits|/b>|br>‧ Simple one step staining procedure in 30 minutes|br>‧ Fast and
TransDetect® Annexin V-EGFP/PI Cell Apoptosis Detection Kit,Cell Detection,Cell Culture and Detection,Products,Beijing TransGen Biotech Co.Ltd,OverviewContents& storageCitations & referencesRelated ImagesDownloadOverviewDescriptionThe Annexin V
Invitrogen™ eBioscience™ Annexin V Apoptosis Detection Kit PerCP-eFluor™ 710 200 tests Invitrogen™ eBioscience™ Annexin V...
Antibodies for proteins involved in negative regulation of cardiac muscle cell apoptotic process pathways, according to their Panther/Gene Ontology Classification
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Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3′-hydroxy-3,4′-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity against human SK-MEL-1 melanoma cells and blocked tubulin polymerization, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. Our analyses showed that flavonoid 7a induces G2-M cell cycle arrest and apoptosis in melanoma cells which is associated with cytochrome c release and activation of both extrinsic and intrinsic apoptotic pathways of cell death ...
TY - JOUR. T1 - Formosanin C-induced apoptosis requires activation of caspase-2 and change of mitochondrial membrane potential. AU - Lee, Jenq Chang. AU - Su, Chun Li. AU - Chen, Lin Lin. AU - Won, Shen Jeu. PY - 2009/4/30. Y1 - 2009/4/30. N2 - Formosanin C is a pure compound isolated from Paris formosana Hayata (Liliaceae). The antitumor efficacy of formosanin C has been observed in cultured cells and animal systems. However, the molecular mechanisms of formosanin C remain unknown. The results of the present study indicate that formosanin C induced apoptosis of HT-29 cells characterized by exposure of phosphatidylserine, accumulation of cells at the sub-G1 phase, fragmentation of DNA, and change of nuclear morphology in a time- and dose-related manner. The apoptotic signaling cascades may proceed via proteolytic activation of caspase-2, change of mitochondrial membrane potential (Δεm), release of cytochrome c and second mitochondria-derived activator of caspase/direct IAP binding protein with ...
This kit is designed for histochemical detection of fragmented DNA using the TUNEL method. It allows quick and easy detection of single cells at the primary stage of apoptosis. Tissue sections and fixed cells may be used for samples.
Tumor Necrosis Apoptosis Inducing Ligand (TRAIL) is a death ligand with some specificity for transformed cells. However, some cancer cells develop resistance to TRAIL allowing escape from immune surveillance. Re-sensitization of these cells to TRAIL depends on identifying the mechanism of resistance and applying a targeted corrective. We studied several possible mechanisms of TRAIL resistance beginning with FLICE-Like Inhibitory Protein (FLIP). The short isoform of FLIP (FLIPshort) is an effective inhibitor of caspase 8 activation and therefore overexpression of FLIPshort may be a mechanism of TRAIL resistance. We found that downregulation of FLIP short was sufficient to re-sensitize some prostate carcinoma cells to TRAIL. Another mechanism we investigated is mediated by Elongation Factor 2 (EF2) which acilitates ribosomal translocation along mRNA strands. EF2 can be inactivated by phosphorylation or by ADP-ribosylation, thereby inhibiting protein synthesis. During inhibition of protein ...
TY - JOUR. T1 - Reversibility of apoptosis in cancer cells. AU - Tang, H. L.. AU - Yuen, K. L.. AU - Tang, H. M.. AU - Fung, M. C.. PY - 2009/1/13. Y1 - 2009/1/13. N2 - Apoptosis is a cell suicide programme characterised by unique cellular events such as mitochondrial fragmentation and dysfunction, nuclear condensation, cytoplasmic shrinkage and activation of apoptotic protease caspases, and these serve as the noticeable apoptotic markers for the commitment of cell demise. Here, we show that, however, the characterised apoptotic dying cancer cells can regain their normal morphology and proliferate after removal of apoptotic inducers. In addition, we demonstrate that reversibility of apoptosis occurs in various cancer cell lines, and in different apoptotic stimuli. Our findings show that cancer cells can survive after initiation of apoptosis, thereby revealing an unexpected potential escape mechanism of cancer cells from chemotherapy.. AB - Apoptosis is a cell suicide programme characterised by ...
Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-a
세포 죽음의 평가에 대한 정확한 방법을 설명합니다. 프로토콜은 세포 라인과 동물 모델의 광범위한 범위에서 기본 세포 40 % 허위 - 긍정적인 이벤트까지 표시 기존 Annexin V / propidium 요오드화물 (PI) 프로토콜에 따라이...
The fourth meeting on dependence receptors featured descriptions of previously unknown dependence receptors. New mechanistic data were presented on the switch between the trophic, antiapoptotic response with the proapoptotic response that occurs with loss of trophic support. The possibility that the loss of trophic support may also involve the binding of an active antitrophin was also discussed. New in vivo data were presented on the roles of dependence receptors in development, angiogenesis, oncogenesis, and neurodegeneration, as well as new therapeutic approaches based on dependence receptor function. The next meeting on dependence receptors is scheduled for 2012.. ...
As soon as Peripheral Blood Mononuclear Cells (PBMC) are isolated from whole blood, some cells begin dying. The rate of apoptotic cell death is increased when PBMC are shipped, cryopreserved, or stored under suboptimal conditions. Apoptotic cells secrete cytokines that suppress inflammation while promoting phagocytosis. Increased numbers of apoptotic cells in PBMC may modulate T cell functions in antigen-triggered T cell assays. We assessed the effect of apoptotic bystander cells on a T cell ELISPOT assay by selectively inducing B cell apoptosis using α-CD20 mAbs. The presence of large numbers of apoptotic B cells did not affect T cell functionality. In contrast, when PBMC were stored under unfavorable conditions, leading to damage and apoptosis in the T cells as well as bystander cells, T cell functionality was greatly impaired. We observed that measuring the number of apoptotic cells before plating the PBMC into an ELISPOT assay did not reflect the extent of PBMC injury, but measuring apoptotic cell
Few things can be considered to be more important to a cell than its threshold for apoptotic cell death, which can be modulated up or down, but rarely in both directions, by a single enzyme. Therefore, it came as quite a surprise to find that one enzyme, glycogen synthase kinase-3 (GSK3), has the pe …
Apoptosis is a genetically regulated form of cell death that occurs when the cell is exposed to physiological, pathogenic, or cytotoxic stimuli. Unregulated apoptosis (too much or too little apoptosis) at any time from embryogenesis to adulthood, can result in a variety of disease states, such as neurodegenerative disorders, autoimmunity, cardiovascular disease, liver and kidney problems, and cancer. A reasonable estimation is that either too little or too much cell death contributes to half of the main medical illnesses for which adequate therapy or prevention is lacking. The apoptotic pathways can be initiated by reactive oxygen species (ROS) and inflammatory molecules, both of which are believed to be up-regulated in a state of obesity. In addition, multiple studies have shown that the risk of developing cardiovascular disease, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and certain types of cancers increase with increasing degree of obesity in both men and women. Despite the ...
AAD positive means late apoptosis? - posted in Flow Cytometry: We have a discussion in the lab about apoptosis detection by annexin V/AAD labeling. Many people say that Annexin V+/AAD+ cells must not be considered apoptotic but necrotic. I agree, provided that the apoptotic stimulus was rather short (for example 2 hours-staurosporine). However, when the stimulus lasts for 24 hours (serum starvation for instance) I think that cells which started the apoptotic process shortly after the start...
Photodynamic therapy (PDT) is considered to be an advancing antitumor technology. PDT using hydrophilic/lipophilic tetra‑α-(4-carboxyphenoxy) phthalocyanine zinc (TαPcZn-PDT) has exhibited antitumor activity in Bel-7402 hepatocellular cancer cells. However, the manner in which p38 MAPK and caspase-9 are involved in the regulation of mitochondria-mediated apoptosis in the TαPcZn-PDT-treated LoVo human colon carcinoma cells remains unclear. Therefore, in the present study, a siRNA targeting p38 MAPK (siRNA-p38 MAPK) and the caspase‑9 specific inhibitor z-LEHD-fmk were used to examine the crosstalk between p38 MAPK and caspase-9 during mitochondria-mediated apoptosis in the TαPcZn-PDT‑treated LoVo cells. The findings revealed that the TαPcZn-PDT treatment of LoVo cells resulted in the induction of apoptosis, the formation of p38 MAPK/caspase-9 complexes, the activation of p38 MAPK, caspase-9, caspase-3 and Bid, the downregulation of Bcl-2, the reduction of mitochondrial membrane ...
This kit is designed for histochemical detection of fragmented DNA using the TUNEL method. It allows quick and easy detection of single cells at the primary stage of apoptosis. Tissue sections and fixed cells may be used for samples.
Data Availability StatementThe datasets used and/or analyzed through the present study are available from your corresponding author on reasonable request. Mouse monoclonal to Chromogranin A RNA. MTT and Annexin V-fluorescein isothiocyanate/propidium iodide assays shown that CLDN1 silencing significantly inhibits proliferation and enhances apoptosis induced by 5-FU treatment in Hep/5FU cells, compared with non-silenced Hep/5FU cells. Additionally, CLDN1 silencing attenuated the migration and invasion capabilities of Hep/5FU cells. In addition, it was recognized that CLDN1 silencing decreased drug resistance by inhibiting autophagy, which was associated with a decrease in the percentage of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I and upregulation of P62. A cell proliferation assay exposed Indotecan the addition of autophagy inhibitor 3-methyladenine decreased drug resistance of Hep/5FU cells. By contrast, incubation with the autophagy agonist Rapamycin elevated drug ...
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal ...
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today ...
SMAC/DIABLO (second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI) is a proapoptotic mitochondrial protein that is released in response to various apoptotic stimuli. Molecular mimetics of SMAC are being investigated for use in cancer treatment, but their activities in vivo have not been fully characterized.. In a recent study, Emeagi and colleagues from Vrije Universiteit Brussel, Belgium, showed that SMAC mimetics induce cancer cell death via a proinflammatory effect that is accompanied by an adaptive antitumor immune response. Transduction with lentiviral vectors encoding a cytosolic form of a SMAC mimetic (LV-tSMAC) resulted in apoptosis of cancer cells of different histologic origins, and treatment of tumor-bearing mice with the SMAC mimetic resulted in induction of apoptosis, activation of antitumor immunity, and prolonged survival.. Immune Response. The antitumor immune response included increased levels of tumor-infiltrating ...
Hochwertige Annexin V FITC Kits für Apoptose Detektion mit Flow Cytometry. ✅ Namhafte Top-Hersteller im Vergleich. ✅ Top-Support bei Fragen.
Albany, New York, Dec 1, 2017: Apoptosis Regulator BAX (Bcl 2 Like Protein 4 or BCL2L4 or BAX) - Apoptosis regulator BAX or bcl-2-like protein 4 is a protein is encoded by the BAX gene. It accelerates programmed cell death by antagonizing the apoptosis repressor BCL2. It promotes activation of CASP3, and thereby apoptosis. It undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis under stress conditions.. Request For Free Sample - Apoptosis Regulator BAX (Bcl 2 Like Protein 4 or BCL2L4 or BAX) pipeline Target constitutes close to 7 molecules. Out of which approximately 3 molecules are developed by companies and remaining by the universities/institutes. The molecules developed by companies in Phase III, Phase II and Preclinical stages are 1, 1 and 1 respectively. Similarly, the universities portfolio in Preclinical and Discovery ...
Heart ischemia can rapidly induce apoptosis and mitochondrial dysfunction via mitochondrial permeability transition-induced cytochrome c release. We tested whether nitric oxide (NO) can block this damage in isolated rat heart, and, if so, by what mechanisms. Hearts were perfused with 50 μM DETA/NO (NO donor), then subjected to 30 min stop-flow ischemia or ischemia/reperfusion. Isolated heart mitochondria were used to measure the rate of mitochondrial oxygen consumption and membrane potential using oxygen and tetraphenylphosphonium-selective electrodes. Mitochondrial and cytosolic cytochrome c levels were measured spectrophotometrically and by ELISA. The calcium retention capacity of isolated mitochondria was measured using the fluorescent dye Calcium Green-5N. Apoptosis and necrosis were evaluated by measuring the activity of caspase-3 in cytosolic extracts and the activity of lactate dehydrogenase in perfusate, respectively. 30 min ischemia caused release of mitochondrial cytochrome c to the cytoplasm
FACS using DAPI for apoptosis analysis - posted in Flow Cytometry: Hello, I am treating cancer cells with a drug and want to analyse cancer cell death. The only problem is that the drug auto-fluoresce a lot, so much that I cannot use conventional viable stains like PI or 7AAD (because sometimes spillover cannot be corrected). I think using DAPI could solve my problem. However, I am not familiar with DAPI. It is often used to determine cell cycle progress, I think, by histology. However,...
Evidence suggests that the signalling events which occur after apoptotic stimulation, define two basic mechanisms for the induction of apoptosis. The first is dependent on signalling via the mitochondria and the second is dependent upon signalling directly from the death receptors. After induction of apoptosis, there is a convergence in signalling at the level of caspase activation and subsequent biochemical and morphological changes. Therefore the efficacy of various inhibitors of apoptosis is dependent upon the initiating signal. In order to understand the apoptotic pathway, the mechanisms by which these inhibitors regulate chemical- and receptor-mediated apoptosis must be understood. The anti-apoptotic oncoprotein, Bcl-2, was shown to inhibit both staurosporine and Fas-mediated apoptosis in a manner which was partially dependent upon the level of Bcl-2 protein expressed. During both staurosporine and Fas-induced apoptosis Bcl-2 acted downstream of caspase-8 activation. High levels of Bcl-2 ...
The influence of diabetes enhanced inflammation on cell apoptosis and periodontitis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Drug resistance has been mostly explained by molecular changes, such as overexpression of p-glycoprotein or O6-methylguanine-DNA-methyltransferase, which interfere with drug actions on the targets (1 , 2) . Because most anticancer agents, regardless of their diverse targets, exert effects by inducing apoptosis via activation of apoptotic pathways common to many cellular stresses, any antiapoptotic changes disrupting the common intrinsic pathways to execute physiological cell death can also make malignant cells resistant to chemotherapy (3) . Such alterations opposing apoptosis are routinely observed in malignant tumors, including both the functional loss of tumor suppressors p53, Bax, or PTEN and deregulated hyperfunction of oncogenic proteins, such as Ras, Bcl-2, and PI3K 2 ,(3) .. In tumor cells with an aberrantly activated PI3K/Akt survival pathway, the increased antiapoptotic signals overcome apoptotic signals of anticancer drugs, confer drug resistance on the tumor cells, and result in a ...
New York - September 19, 2019 - BOC Sciences, a New York-based supplier of various bio-chemicals such as inhibitors, APIs, metabolites and impurities, announced earlier this month to launch cell apoptosis assay service for scientists engaged in drug discovery research. With expertise and well-published cell based assays from BOC Sciences, researchers now dont need to worry about apoptosis detection anymore.. Apoptosis, or alternatively referred to as programmed cell death, plays an important role in many human diseases. Controlled by multiple signaling and effector pathways, apoptosis is found to be closely linked with caspase related apoptotic enzyme cascades, mitochondrial depolarization, DNA fragmentation and ultimately cell blebbing and destruction. This offers new insights for scientists who are seeking new treatment for various diseases: through approaches of genetically modulating these apoptosis-associated pathways, new therapies might be discovered. Many human conditions like ...
Apoptosis is characterized by a series of well defined morphological and biochemical features that allow cells to initiate self-destruction in response to a variety of stimuli. CD4⁺CD8⁺ is a sub-population of immature thymocytes that are especially prone to the action of apoptosis-inducing agents and are sensitive to glucocorticoid-induced apoptosis, an event that plays a critical role in eliciting the antigen-specific thymocyte repertoire. Glucocorticoids induce apoptosis through activation of the GR, a ligand-induced transcription factor that transduces the hormonal signals into the regulated expression of target genes. While much is known about the structure and function of GR, key steroid-regulated genes believed to be required for thymocyte apoptosis have not been found. Based on the transcriptional-regulation of apoptosis by ecdysone-mediated induction of reaper gene expression in Drosophila, and p53-mediated transcriptional-activation of Bax gene expression in mammalian cells, our ...
Zeng L., Li T., Xu D.C., Liu J., Mao G., Cui M.Z., Fu X., Xu X.. Cells undergo apoptosis through two major pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway). These two pathways can be linked by caspase-8-activated truncated Bid formation. Very recently, death receptor 6 (DR6) was shown to be involved in the neurodegeneration observed in Alzheimer disease. DR6, also known as TNFRSF21, is a relatively new member of the death receptor family, and it was found that DR6 induces apoptosis when it is overexpressed. However, how the death signal mediated by DR6 is transduced intracellularly is not known. To this end, we have examined the roles of caspases, apoptogenic mitochondrial factor cytochrome c, and the Bcl-2 family proteins in DR6-induced apoptosis. Our data demonstrated that Bax translocation is absolutely required for DR6-induced apoptosis. On the other hand, inhibition of caspase-8 and knockdown of Bid have no effect on DR6-induced ...
Apoptosis is a normal physiological process which eliminates cells that do not receive adequate extracellular signals. One of the pathways signalling apoptosis is controlled by the small GTPases of the Rho family, also involved in cell proliferation, differentiation and motility. Another major apoptosis signalling pathway involves the p53 tumour suppressor which is activated by a variety of stress and mediates growth arrest or apoptosis in normal cells. We show here that upon detachment from the extracellular matrix, fibroblasts undergo rapid apoptosis that can be rescued by constitutive activation of Rac1 and Cdc42Hs GTPases. Conversely, inhibition of Rac1 and Cdc42Hs efficiently triggers apoptosis in adherent cells. Interestingly, apoptosis is not observed in p53-/- cells either cultured in suspension or inhibited for Rac1 and Cdc42Hs activity. Moreover, Rac1 and Cdc42Hs extinction in normal cells activates endogenous p53. Using specific inhibitors of MAPK pathways, we demonstrate that, in our ...
As one of the cellular death mechanisms, apoptosis, also known as programmed cell death, can be defined as the process of a proper death of any cell under certain or necessary conditions. Apoptosis is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body.. Many biochemical events and a series of morphological changes occur at the early stage and increasingly continue till the end of apoptosis process. Morphological event cascade including cytoplasmic filament aggregation, nuclear condensation, cellular fragmentation, and plasma membrane blebbing finally results in the formation of apoptotic bodies. Several biochemical changes such as protein modifications/degradations, DNA and chromatin deteriorations, and synthesis of cell surface markers form morphological process during apoptosis.. Apoptosis can be stimulated by two different pathways: (1) intrinsic pathway (or mitochondria pathway) that mainly occurs via release of ...
Explore EarlyTox Caspase-3/7 NucView 488 Assay Kits that enables detection of apoptosis within intact cell populations through the use of NucView 488 Caspase-3 substrate.
The detection of DNA fragmentation by the use of the TUNEL technique has become a standard technique for the detection of apoptosis in tissue sections. DNA cleavage, detected by the TUNEL technique, is the last irreversible stage of the apoptosis cascade. When the nuclear DNA is cleaved in oligonucl …
Annexin V-Biotin Apoptosis Reagent (ab14165). Quick and reliable detection of phosphatidylserine exposure by flow cytometry or microscopy.
The molecular nature of calcium (Ca(2+))-dependent mechanisms and the ion channels having a major role in the apoptosis of cancer cells remain a subject of debate. Here, we show that the recently identified Orai1 protein represents the major molecular component of endogenous store-operated Ca(2+) entry (SOCE) in human prostate cancer (PCa) cells, and constitutes the principal source of Ca(2+) influx used by the cell to trigger apoptosis. The downregulation of Orai1, and consequently SOCE, protects the cells from diverse apoptosis-inducing pathways, such as those induced by thapsigargin (Tg), tumor necrosis factor α, and cisplatin/oxaliplatin. The transfection of functional Orai1 mutants, such as R91W, a selectivity mutant, and L273S, a coiled-coil mutant, into the cells significantly decreased both SOCE and the rate of Tg-induced apoptosis. This suggests that the functional coupling of STIM1 to Orai1, as well as Orai1 Ca(2+)-selectivity as a channel, is required for its pro-apoptotic effects. We have
For a TUNEL assay, dissolve DNase I in 50 mM Tris-HCl, pH 7.5, 1 mg/ml BSA. The final concentration will depend on the sample being processed. In general, start by using a low concentration (1 U/ml for 10 min at +15 to +25 °C). This procedure is described in the pack inserts of the In Situ Cell Death Detection Kits. Follow the steps described in the troubleshooting section of the pack inserts of the In Situ Cell Death Detection Kits when having problems with positive controls ...
Bullacta exarata was hydrolyzed with trypsin to prepare peptides; Hydrolysates were isolated by ultrafiltration and purified using G-25 gel filtration. The purity of the Bullacta exarata was demonstrated by HPLC and its peptide sequence analysis was detected. The effects of BEPT II and BEPT II-1 on the proliferation of PC-3 cells were examined using a MTT assay. BEPT II and BEPT II-1 significantly inhibited the proliferation of PC-3 cells in a time- and dose-dependent manner. Annexin V/PI double staining studies showed exposing PC-3 cells to 5, or 15 mg/mL BEPT II-1 for 24 h increased the percentage of the early stage of apoptotic cells from 11.22% to 22.09%. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. These data support that BEPT II-1 has anticancer properties and merits further investigation to understand the mechanisms of BEPT II-1-induced apoptosis in PC-3 cells.
The BCL-2 family of proteins forms a complex interaction network that regulates cellular life and death decisions and contributes to cancer development, maintenance, and chemoresistance. BH3 only member proteins (e.g. BIM) serve as cellular stress sentinels and, when triggered, signal irreversible activation of apoptosis through their α-helical BH3 death domains. These pro-apoptotic signals are normally held in check by the multidomain anti-apoptotic proteins (e.g. BCL-XL, MCL-1) but when they are unable to do so the multidomain pro-apoptotic proteins BAX and BAK induce cell death through pore formation in the mitochondrial outer membrane. Therapeutic manipulation of the BCL-2 family with BH3 mimetics (including small molecules and synthetic peptides) is an emerging paradigm in cancer treatment and immune modulation. The design of next-generation therapeutics based on the BIM BH3 helix offers the unique advantage of recapitulating BIMs natural capacity to directly target the full complement of ...
Mice and primary neuronal cultures. Hq, Apaf1-/-, and Bax-/- mice were maintained and genotyped as described previously (Fortin et al., 2001; Klein et al., 2002). Cortical neurons and cerebellar granule neurons (CGNs) were cultured from cortices of E15.5 mice and cerebellums of postnatal day 7 mice, respectively, as described previously (Fortin et al., 2001). Recombinant adenoviral vectors carrying human AIF or LacZ expression cassettes were prepared and used at 50 multiplicity of infection as described previously (Cregan et al., 2002).. Camptothecin treatment and cell viability assays. Neurons were treated with 10 μm camptothecin with or without 10 μm Boc-aspartyl (Ome)-fluoromethylketone (BAF) (Enzyme System Products, Livermore, CA) after 2 d in vitro (DIV). Cell survival was measured by the following: live/dead staining (Molecular Probes, Eugene, OR), Hoechst staining, MTT assay (Cell Titer kit; Promega, Madison, WI), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end ...
TY - JOUR. T1 - Molecular cloning of a human cDNA encoding a novel protein, DAD1, whose defect causes apoptotic cell death in hamster BHK21 cells. AU - Nakashima, Torahiko. AU - Sekiguchi, Takeshi. AU - Kuraoka, Akio. AU - Fukushima, Kohtarou. AU - Shibata, Yosaburo. AU - Komiyama, Sohtaro. AU - Nishimoto, Takeharu. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 1993/10. Y1 - 1993/10. N2 - The tsBN7 cell line, one of the mutant lines temperature sensitive for growth which have been isolated from the BHK21 cell line, was found to die by apoptosis following a shift to the nonpermissive temperature. The induced apoptosis was inhibited by a protein synthesis inhibitor, cycloheximide, but not by the bcl-2-encoded protein. By DNA-mediated gene transfer, we cloned a cDNA that complements the tsBN7 mutation. It encodes a novel hydrophobic protein, designated DAD1, which is well conserved (100% identical amino acids between humans and hamsters). By comparing the base sequences ...
Introduction Internucleosomal cleavage of DNA is a hallmark of apoptosis. DNA cleavage in apoptotic cells can be detected in situ in fixed cells or tissue sections using the terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) method. TUNEL is highly selective for the detection of apoptotic cells but not necrotic cells or cells with DNA strand breaks resulting from irradiation or drug treatment. In the TUNEL assay, TdT enzyme catalyzes the addition of labeled dUTP to the 3 ends of cleaved DNA fragments. Hapten-tagged dUTP (e.g. digoxigenin-dUTP or biotin-dUTP) can be detected using secondary reagents (e.g. anti-digoxigenin antibodies or streptavi-din) for fluorescence or colorimetric detection. Alternatively, fluorescent dye-conjugated dUTP can be used for direct detection of fragmented DNA by fluorescence microscopy or flow cytometry. The TUNEL Andy Fluor™ 594 Apoptosis Detection Kit contains dUTP conjugated to biotin and Streptavidin conjugated to bright and ...
The purpose of this study is to determine if a preventive treatment with curcumin can protect intestinal epithelial cells from inflammatory damage induced by IFNγ. To achieve this goal we have used a human intestinal epithelial cell line (HT29) treated with IFNγ to undergo apoptotic changes that can reproduce the damage of intestinal epithelia exposed to inflammatory cytokines. In this model, we measured the effect of curcumin (curcuminoid from Curcuma Longa) added as a pre-treatment at different time intervals before stimulation with IFNγ. Curcumin administration to HT29 culture before the inflammatory stimulus IFNγ reduced the cell apoptosis rate. This effect gradually declined with the reduction of the curcumin pre-incubation time. This anti-apoptotic action by curcumin pre-treatment was paralleled by a reduction of secreted IL7 in the HT29 culture media, while there was no relevant change in the other cytokine levels. Even though curcumin pre-administration did not impact the activation of the
TY - JOUR. T1 - Mifepristone regulates expression of apoptosis related genes Fas and FasL in mouse endometrium. AU - Gao, F.. AU - Xu, F. H.. AU - Zhou, X. C.. AU - Han, X. B.. AU - Liu, Y. X.. PY - 2001/7/3. Y1 - 2001/7/3. N2 - AIM: To investigate the anti-implantation mechanism of mifepriston. METHODS: In situ hybridization and immunohistochemistry were applied to determine mRNA and protein. RESULTS: After mifepriston injection, the number of implantation sites were obviously reduced, mifepriston could inhibit the embryo implantation in mouse. The expression of apoptosis related genes, Fas and FasL, in mouse endometrium was also decreased after mifepriston treatment. CONCLUSION: The expression of apoptosis related genes Fas and FasL is regulated by mifepriston and the inhibitory effect of mifepriston on the embryo implantation may be mediated by action on the Fas/FasL system.. AB - AIM: To investigate the anti-implantation mechanism of mifepriston. METHODS: In situ hybridization and ...
title: Galpha12 Protects Vascular Endothelial Cells from Serum Withdrawal-Induced Apoptosis through Regulation of miR-155, doi: 10.3349/ymj.2016.57.1.247, category: Article
Vascular Endothelial Growth Inhibitor (VEGI) is an endothelial cell autocrine factor and a member of the tumor necrosis family of ligands. VEGI is able to specifically inhibit endothelial cell growth and is an efficient inhibitor of angiogenesis. The molecular mechanisms of VEGI activity on endothelial cells remain undefined. Here we focused on two important steps in the signal transduction of VEGI. We first determined a role of NF-κB in VEGI-induced apoptosis. We found that inhibition of the NF-κB pathway resulted in an increased apoptotic potential of VEGI. We conclude that the NF-κB pathway plays a role in suppressing the apoptotic potential of VEGI. We next investigated the receptor responsible for VEGI-induced endothelial cell apoptosis. DR3 is a receptor for VEGI and thus we first focused on confirming if DR3 is the receptor responsible for VEGI-mediated endothelial cell death. We determined VEGI had diminished apoptotic activity in endothelial cells that are depleted of DR3 by siRNA. ...
HOTAIR was known to enhance radioresistance in several cancers. However, the function of HOTAIR on radioresistance involving the regulation of HIF-1α in cervical cancer has not been reported. BALB/c nude mice were injected subcutaneously with HeLa cells and irradiated by X-ray. The tumor volume was measured and the expression of HOTAIR in tumors was detected by quantitative real-time PCR. Western blot was performed to detect the protein level of HIF-1α. MTT (3-(4,5-Dimethylthiazol-2-yl) 22,5-diphenyltetrazolium bromide) assay and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to examine the cell viability and cell apoptosis of HeLa cells and C33A cells exposed to radiation. Radiotherapy inhibited the tumor growth in mice bearing HeLa cells. Radiotherapy reduced the expression of HOTAIR and HIF-1α in tumor tissues and HeLa cells or C33A cells. HOTAIR overexpression abrogated the effect of radiation on the cell viability and cell apoptosis of HeLa and C33A cells
Methods and Findings: Studies were performed using wild type (WT) and A2 knockout (A2-/-) mice exposed to Oxygen Induced Retinopathy (OIR). Neuronal injury and apoptosis were assessed using immunohistochemistry, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end) labeling and Western blotting. Electroretinography (ERG) was used to assess retinal function. Neuro-glial injury in WT ROP mice was evident by TUNEL labeling, retinal thinning, decreases in number of rod bipolar cells and glial cell activation as compared with room air controls. Significant reduction in numbers of TUNEL positive cells, inhibition of retinal thinning, preservation of the rod bipolar cells and prevention of glial activation were observed in the A2-/- retinas. Retinal function was markedly impaired in the WT OIR mice as shown by decreases in amplitude of the b-wave of the ERG. This defect was significantly reduced in A2-/- mice. Levels of the pro-apoptotic proteins p53, cleaved caspase 9, cytochrome C and the ...
Pure ginsenoside standards (saponins Rh2, PD, and PT), along with an Rh2-enhanced North American ginseng (Panax quinquefolius) leaf extract (LFRh2), were tested for cytotoxic activity in cultured THP-1 leukemia cells. Thermal treatment of ginseng leaf resulted in production of both Rh2 and Rg3 content that was confirmed by liquid chromatography-mass spectrometry (LC-MS). Flow cytometry of cells stained with annexin V-fluorescein isothiocyanate and propidium iodide showed that the LFRh2 significantly (p ≤ 0.05) increased apoptosis (18% ± 0.4%) after 23 h at a concentration that inhibited cell viability by 50% (LC50 (72 h) = 52 μmg/mL. In comparison, a similar significant (p ≤ 0.05) increase in apoptotic cell numbers occurred at 41 h of exposure for pure ginsenoside standards, PD (LC50 (72 h) = 13 μg/mL), PT (LC50 (72 h) = 19 μg/mL), and Rh2 (LC 50 (72 h) = 15 μg/mL). Although no further increase in apoptosis was observed in THP-1 cells after exposure to increasing concentrations of LFRh2 ...
TY - JOUR. T1 - FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. AU - Chinnaiyan, Arul M.. AU - Tepper, Clifford G. AU - Seldin, Michael F. AU - ORourke, Karen. AU - Kischkel, Frank C.. AU - Hellbardt, Stefan. AU - Krammer, Peter H.. AU - Peter, Marcus E.. AU - Dixit, Vishva M.. PY - 1996/3/1. Y1 - 1996/3/1. N2 - CD95 (Fas/APO-1) and tumor necrosis factor receptor-1 (TNFR-1) are related molecules that signal apoptosis. Recently, a number of novel binding proteins have been proposed to mediate the signaling of these death receptors. Here we report that an N-terminal truncation of one of these candidate signal transducers, FADD/MORT1, abrogates CD95-induced apoptosis, ceramide generation, and activation of the cell death protease Yama/CPP32. In addition, this dominant-negative derivative of FADD (FADD-DN) blocked TNF- induced apoptosis while not affecting NF-κB activation. FADD-DN bound both receptors, and in the case of CD95, it disrupted ...
In this paper, the use of (123)I-Annexin V for the detection of farnesyltransferase inhibitor (FTI)-induced apoptosis in tumour-bearing athymic mice is described. In vitro binding assays on LoVo cells show time- and dosage-dependent (125)I-Annexin V binding upon treatment with Tipifarnib (Zarnestra,
Paclitaxel is used to treat breast cancers, but the mechanisms by which it induces apoptosis are poorly understood. Consequently, we have studied the role of the FoxO transcription factors in determining cellular response to paclitaxel. Western blotting revealed that in a panel of nine breast cancer cell lines expression of ... read more FoxO1a and FoxO3a correlated with the expression of the pro-apoptotic FoxO target Bim, which was associated with paclitaxel-induced apoptosis. In MCF-7 cells, which were paclitaxel-sensitive, the already high basal levels of FoxO3a and Bim protein increased dramatically after drug treatment, as did Bim mRNA, which correlated with apoptosis induction. This was not observed in MDA-231 cells, which expressed low levels of FoxOs and Bim. Gene reporter experiments demonstrated that in MCF-7 cells maximal induction of Bim promoter was dependent on a FoxO binding site, suggesting that FoxO3a is responsible for the transcriptional up-regulation of Bim. Gene silencing ...
Objectives : We investigated the effect of Haein-tang(Hairen-tang) on short-term memory and apoptosis in dentate gyrus of the gerbils with transient global ischemia. Methods : For the induction of cerebral ischemia model in mice, common carotid arteries of gerbils were occluded with aneurysm clips for 5 min. One day after operation, Haein-tang(Hairen-tang) was administrated orally injected once a day for 15 consecutive days. Gerbils were randomly divided into four group(n=10 in each group): sham-operation group, ischemia-induction group, ischemia-induction and 50 mg/kg Haein-tang(Hairen-tang)-treated group, ischemia-induction and 100 mg/kg Haein-tang(Hairen-tang)-treated group, and ischemia-induction and 200 mg/kg Haein-tang(Hairen-tang)-treated group. The effect of Haein-tang(Hairen-tang) on memory function was investigated by using step-down avoidance task. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining and immunohistochemistry ...
We used cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway to analyse the events of apoptotic exe-cution. So-called S/M extracts from morphologically normal committed-stage cells induce apoptotic morphology and DNA cleavage in substrate nuclei. These apoptotic changes appear to require the function of multiple caspases (cysteine aspar-tases, a specialized class of proteases) acting in parallel. Extracts from execution-stage apoptotic cells induce apoptotic events in added nuclei in a caspase-independent manner. Biochemical frac-tionation of these extracts reveals that a column fraction enriched in endogenous active caspases is un-able to induce DNA fragmentation or chromatin condensation in substrate nuclei, whereas a caspase-depleted fraction induces both changes. Execution-stage extracts contain an ICAD/DFF45-inhibitable nuclease resembling CAD, plus another activity that is required for the apoptotic chromatin condensation. Committed-stage S/M ...
As a process, apoptosis integrates a multitude of pro- and anti-cell death signals to a single decision for life or death. This type of all-or-none response to quantitative inputs is common in biological phenomena such as cell proliferation and differentiation and is often associated with a network topology containing positive feedback loops (28). While the ability of caspases to self-cleave provides one level of such feedback activity (17), we find that this feedback extends to cross activation between both the extrinsic and intrinsic pathways, with specific activation of either extrinsic or intrinsic apoptosis leading to near simultaneous activation of both caspase-8 and -9 in all apoptotic cells tested in this experiment. This supports a model wherein, although initiation of caspases is segregated by distinct pathways, an apoptotic signal, once having reached a threshold level, leads to a simultaneous activation across both arms of the apoptotic network. Several signaling mechanisms ...
In previous study we showed that caspase-2 plays the role of an apical caspase in cell death induction by taxanes in breast cancer cells. This study deals with the role of other caspases. We tested breast cancer cell lines SK-BR-3 (functional caspase-3) and MCF-7 (nonfunctional caspase-3). Using western blot analysis we demonstrated the activation of initiator caspase-8 and -9 as well as executioner caspase-6 and -7 in both tested cell lines after application of taxanes (paclitaxel, SB-T-1216) at death-inducing concentrations. Caspase-3 activation was also found in SK-BR-3 cells. Employing specific siRNAs after taxane application, suppression of caspase-3 expression significantly increased the number of surviving SK-BR-3 cells. Inhibition of caspase-7 expression also increased the number of surviving SK-BR-3 and MCF-7 cells. On the other hand, suppression of caspase-8 and caspase-9 expression had no significant effect on cell survival. However, caspase-9 seemed to be involved in the activation of
TY - JOUR. T1 - Calcineurin Aβ Gene Targeting Predisposes the Myocardium to Acute Ischemia-Induced Apoptosis and Dysfunction. AU - Bueno, Orlando F.. AU - Lips, Daniel J.. AU - Kaiser, Robert A.. AU - Wilkins, Benjamin J.. AU - Dai, Yan Shan. AU - Glascock, Betty J.. AU - Klevitsky, Raisa. AU - Hewett, Timothy E.. AU - Kimball, Thomas R.. AU - Aronow, Bruce J.. AU - Doevendans, Pieter A.. AU - Molkentin, Jeffery D.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2004/1/9. Y1 - 2004/1/9. N2 - Cardiovascular disease is the leading cause of mortality and morbidity within the industrialized nations of the world, with coronary heart disease (CHD) accounting for as much as 66% of these deaths. Acute myocardial infarction is a typical sequelae associated with long-standing coronary heart disease resulting in large scale loss of ventricular myocardium through both apoptotic and necrotic cell death. In this study, we investigated the role that the calcium calmodulin-activated ...
TY - JOUR. T1 - Nitrite generation and antioxidant effects during neutrophil apoptosis. AU - Misso, Neil L.A.. AU - Peacock, Craig D.. AU - Neil Watkins, D.. AU - Thompson, Philip J.. PY - 2000/3/15. Y1 - 2000/3/15. N2 - Neutrophil apoptosis is important for the resolution of airway inflammation in a number of lung diseases. Inflammatory mediators, endogenous reactive oxygen and nitrogen species, and intracellular and extracellular antioxidants may all influence neutrophil apoptosis. This study investigated the involvement of these factors during apoptosis of neutrophils cultured in vitro. Neutrophils undergoing spontaneous apoptosis in culture as assessed by annexin V binding generated significant amounts of nitrite. Incubation with agonistic anti-Fas monoclonal antibody or tumor necrosis factor-α (TNF-α) enhanced neutrophil apoptosis at 6 h, although it decreased nitrite accumulation. Although granulocyte-macrophage colony-stimulating factor significantly reduced neutrophil apoptosis, this ...
Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.
TY - JOUR. T1 - Pretreatment with low nitric oxide protects osteoblasts from high nitric oxide-induced apoptotic insults through regulation of c-Jun N-terminal kinase/c-Jun-mediated Bcl-2 gene expression and protein translocation. AU - Tai, Yu-Ting. AU - Cherng, Yih-Giun. AU - Chang, Chia Chen. AU - Hwang, Yi Ping. AU - Chen, Jui Tai. AU - Chen, Ruei-Ming. PY - 2007/5. Y1 - 2007/5. N2 - Nitric oxide (NO) can regulate osteoblast activity. In this study, we evaluated the effects of pretreatment with a low concentration of NO on osteoblast injuries induced by a high level of NO and its possible molecular mechanisms. Exposure of osteoblasts to 0.3 mM sodium nitroprusside (SNP), an NO donor, slightly increased cellular NO levels without affecting cell viability. SNP at 2 mM greatly increased the levels of cellular NO and reactive oxygen species, and induced osteoblast death. Thus, osteoblasts were treated with 0.3 and 2 mM SNP as the sources of low and high NO, respectively. Exposure of osteoblasts ...
Because defects in apoptosis programs, for example, high expression of antiapoptotic molecules, can cause resistance to treatment regimens including radiotherapy (8), current attempts to improve the outcome of glioblastoma patients depend on strategies to increase apoptosis sensitivity. In this study, we identify a new proapoptotic role of NF-κB in γ-irradiation-mediated apoptosis of glioblastoma cells by showing, for the first time, that NF-κB is critically required for Smac mimetic-triggered radiosensitization. This conclusion is supported by several independent pieces of evidence. First, BV6 and γ-irradiation cooperate to trigger apoptosis in glioblastoma cells. This interaction is highly synergistic in A172 glioblastoma cells (CI , 0.3). Second, BV6 stimulates NF-κB activation, which is required for the potentiation of γ-irradiation-induced apoptosis because genetic inhibition of NF-κB by overexpression of the dominant-negative superrepressor IκBα-SR significantly reduces BV6- and ...
TY - JOUR. T1 - Nitric oxide-GAPDH-Siah. T2 - a novel cell death cascade.. AU - Hara, Makoto R.. AU - Snyder, Solomon H. PY - 2006/7. Y1 - 2006/7. N2 - 1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extremely abundant glycolytic enzyme, and exemplifies the class of proteins with multiple, seemingly unrelated functions. Recent studies indicate that it is a major intracellular messenger mediating apoptotic cell death. This paper reviews the GAPDH cell death cascade and discusses its clinical relevance. 2. A wide range of apoptotic stimuli activate NO formation, which S-nitrosylates GAPDH. The S-nitrosylation abolishes catalytic activity and confers upon GAPDH the ability to bind to Siah, an E3-ubiquitin-ligase, which translocates GAPDH to the nucleus. In the nucleus, GAPDH stabilizes the rapidly turning over Siah, enabling it to degrade selected target proteins and affect apoptosis. 3. The cytotoxicity of mutant Huntingtin (mHtt) requires nuclear translocation which appears to be ...
3H]Thymidine Incorporation Studies. Thymidine incorporation studies were performed with cells grown in 35-mm culture dishes. The cells were labeled by the addition of methyl-[3H]thymidine (1 μCi/ml) to the medium, and the reactions were stopped after 1 h. The medium was drawn off, and the cells were rinsed twice with ice-cold phosphate-buffered saline (PBS). The cultures were then fixed with ice-cold 5% trichloracetic acid overnight at 4°C, after which the cells were extracted as previously described (Guo and Reiners, 2000). A second replicate set of nonfixed dishes was treated with 0.25% trypsin-EDTA to estimate cell numbers. [3H]Thymidine was detected by scintillation counting and expressed as disintegration per minute per 103 cells.. Assessment of Apoptosis. The effects of HET0016 to induced apoptosis in 9L cells were examined by fluorescence-activated cell sorting analysis after the cells were labeled with an annexin V-fluorescein isothiocyanate (FITC) antibody (Sigma Chemical, St. Louis, ...
Previous studies suggested that dithio-carbamates are potent apoptosis and anti-apoptosis inducing agents in various cancer cells. Here, the anti-proliferative and apoptosis inducing effects of a new derivative (2-NDC) from the dithio-carbamate family was examined in human leukemia K562 cells. We use thiazolyl blue tetrazolium bromide (MTT) to measure viability and cell growth inhibition. The 2-NDC showed effects on viability in a dose and time-dependent manner, inhibiting proliferation at concentrations of 10-30 M after 24-48 hours of treatment and increasing values after 72 hours at 40-120 M. The cytotoxic effect of the compound was calculated with an IC50 of 30 M after 24-hour. Apoptosis induction was confirmed by acridine orange-ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, flow cytometric assessment and also caspase-3 activation assay. Furthermore, enzymes level such as superoxide dismutase (SOD) and catalase (CAT) involved in oxidative stress were evaluated. The results of this
Our results uncovered an unexpected role for MPO to influence the fate of neutrophils and consequently the duration of inflammation. By suppressing the constitutive cell death program, MPO prolonged the life span of neutrophils, thereby delaying the resolution of inflammation. These actions were specific for MPO, because other azurophilic granule constituents lactoferrin and elastase failed to affect neutrophil apoptosis.. Consistent with the commitment of neutrophils to apoptosis, MPO at clinically relevant concentrations delayed, rather than blocked apoptosis, resulting in prolonged survival of human neutrophils in vitro. We confirmed that increasing plasma concentrations of MPO in rats to levels comparable to those detected in patients with inflammatory vascular diseases20,21 was sufficient to retard the apoptotic machinery in neutrophils as assayed ex vivo. Furthermore, MPO also suppressed apoptosis in neutrophils that had emigrated into the airways and delayed resolution of inflammation in ...
The effects of the acute phase proteins AGP and AAT on early (2-hour) and late (24-hour) apoptosis and inflammation after renal I/R were investigated. Both AGP and AAT administered at reperfusion decrease early as well as late apoptosis, as reflected by renal internucleosomal DNA cleavage, TUNEL histology, and caspase-like activities. In line, we previously demonstrated that abrogating acute early apoptosis with selective antiapoptotic agents prevents subsequent inflammation as well as secondary apoptosis caused by inflammation, whereas antiapoptotic treatment that is initiated after the onset of apoptosis does not reduce I/R-induced inflammation.1 In contrast, in the present study, treatment after 2 hours of reperfusion inhibited inflammation, which is supported by reports of anti-inflammatory effects mediated by AGP and AAT.12 13 Early primary19 20 as well as late secondary2 21 apoptosis after I/R has been reported to be caused by various means. The present results, showing that AGP and (to a ...
TY - JOUR. T1 - Response of Apoptosis Related Proteins to Running in Fluoride-Exposed Mice. AU - Canning, M.. AU - Zohoori, Fatemeh. AU - Valentine, Ruth. AU - Khan, Z.. AU - Ahmed, A.. AU - Amaral, A.. AU - Azevedo, Liane. AU - Buzalaf, Maria. AU - Fabricio, M.. AU - Fernandes, M.. AU - Maguire, Anne. PY - 2017. Y1 - 2017. M3 - Meeting Abstract. VL - 96A. JO - Journal of Dental Research. JF - Journal of Dental Research. SN - 0022-0345. ER - ...
An in vitro ischemia model was established and the effect of the metabolic inhibitors cycloheximide (CHX) and actinomycin D (ActD) on apoptosis in astrocytes under ischemia studied. CHX decreased by 75% the number of cells dying after 6 hr of ischemia compared with control cultures. TdT-mediated dUTP nick end labelling (TUNEL) staining of comparable cultures was reduced by 40%. ActD decreased cell death by 60% compared with controls. The number of TUNEL-positive cells was reduced by 38%. The nuclear shrinkage in TUNEL-positive astrocytes in control cultures did not occur in ActD-treated astrocytes, indicating that nuclear shrinkage and DNA fragmentation during apoptosis are two unrelated processes. Expression of bcl-2 (alpha and beta), bax, and Ice in astrocytes under similar ischemic conditions, as measured by quantitative reverse transcription-polymerase chain reaction, indicated that ischemia down-regulated bcl-2 (alpha and beta) and bax. Ice was initially down-regulated from 0 to 4 hr, ...
AIMS--To compare in situ end-labelling (ISEL) of apoptosis in lung carcinoma with quantitative and semiquantitative light microscopic assessment and ultrastructural observations. METHODS--ISEL of apoptosis was evaluated in 42 lung carcinomas (24 squamous cell carcinomas, 12 adenocarcinomas and six small cell carcinomas). Results were correlated semiquantitatively with the extent of apoptosis in haematoxylin and eosin stained sections, with apoptotic indices and with ultrastructural observations (nine cases). RESULTS--In each tumour type the extent of apoptosis identified by ISEL correlated with that observed on light and electron microscopy. Tumour cells undergoing apoptosis showed either uniform nuclear staining with a surrounding halo or peripheral nuclear membrane staining. The latter pattern was more prominent in small cell carcinoma and correlated ultrastructurally with early apoptosis. A variable proportion of apoptotic cells and apoptotic bodies were unlabelled. Necrotic tumour cells ...
TY - JOUR. T1 - Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. AU - Condorelli, Gianluigi. AU - Morisco, Carmine. AU - Stassi, Giorgio. AU - Notte, Antonella. AU - Farina, Felicia. AU - Sgaramella, Giuseppe. AU - De Rienzo, Assunta. AU - Roncarati, Roberta. AU - Trimarco, Bruno. AU - Lembo, Giuseppe. PY - 1999/6/15. Y1 - 1999/6/15. N2 - Background - Left ventricular hypertrophy (LVH) represents both an adaptive response to increased cardiac work load and a precursor state of heart failure. Recent evidence linked cardiac myocyte death by apoptosis with LVH and heart failure. It remained unclear, however, whether apoptosis participated in the transition from LVH to left ventricular dysfunction (LVD). Methods and Results - Cardiac myocyte apoptotic events and changes in apoptosis-specific genes were studied in a rat model of chronic pressure overload induced by ...
Animals and plants diverged over one billion years ago and evolved unique mechanisms for many cellular processes, including cell death. One of the most well-studied cell death programmes in animals, apoptosis, involves gradual cell dismantling and engulfment of cellular fragments, apoptotic bodies, through phagocytosis. However, rigid cell walls prevent plant cell fragmentation and thus apoptosis is not applicable for executing cell death in plants. Furthermore, plants are devoid of the key components of apoptotic machinery, including phagocytosis as well as caspases and Bcl-2 family proteins. Nevertheless, the concept of plant
When hypertonicity is imposed with sufficient intensity and acuteness, cells die. Here we investigated the cellular pathways involved in death using a cell line derived from renal epithelium. We found that hypertonicity rapidly induced activation of an intrinsic cell death pathway- release of cytochrome c and activation of caspase-3 and caspase-9-and an extrinsic pathway-activation of caspase-8. Likewise, a lysosomal pathway of cell death characterized by partial lysosomal rupture and release of cathepsin B from lysosomes to the cytosol was also activated. Relationships among the pathways were examined using specific inhibitors. Caspase inhibitors did not affect cathepsin B release into the cytosol by hypertonicity. In addition, cathepsin B inhibitors and caspase inhibitors did not affect hyper-tonicity-induced cytochrome c release, suggesting that the three pathways were independently activated. Combined inhibition of caspases and cathepsin B conferred significantly more protection from ...
Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction represents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoids are a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-rich polyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitro and in vivo.. The results highlight an important, previously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarp extracts.. Journal of Medicinal Food, Volume: 7 Issue 1: July 7, 2004 ...
TY - JOUR. T1 - Reduced wall compliance suppresses Akt-dependent apoptosis protection stimulated by pulse perfusion. AU - Li, Manxiang. AU - Chiou, Kuan Rau. AU - Bugayenko, Artem. AU - Irani, Kaikobad. AU - Kass, David A.. PY - 2005/9/16. Y1 - 2005/9/16. N2 - Reduced arterial compliance and increased pulse pressure are common and major risk factors for cardiovascular disease. Here, we reveal a novel mechanism whereby loss of wall distensibility blunts endothelial cell protection to oxidant stress-induced apoptosis. Bovine aortic endothelial cells cultured in compliant or stiff silastic tubes were pulse perfused by arterial pressure/flow waveforms generated by a servo-pump. Pulse perfusion induced time-dependent Akt activation peaking ,6-fold after 2 hours in compliant tubes and a similar time course but half the magnitude in stiff tubes. This was accompanied by quantitatively similar disparities in phosphoinositide-3 kinase activation and in Akt-stimulated suppressors of apoptosis: glycogen ...
Worldwide Market Reports added Latest Research Report titled Global Apoptosis Assays Market Is Expected To Reach Around USD 6.96 Billion By 2025″ to its Large Report database. The report, the global Apoptosis Assays Market, demonstrates an all-encompassing investigation of the global Apoptosis Assays Market that appraises the market magnitude and evaluates the market assessment above the predicted time. The ruling players of the Apoptosis Assays Market are visible inside the report in company with thorough details referring to their revenue break-up, synopsis of the business, latest developments, product segmentation, and so on. The operative market players in the global Apoptosis Assays Market are further discussed in the report.. This Research will help you grow your Business: [Download free Sample PDF of This Research Report]. Some of the Major Apoptosis Assays Market Players Are:. Merck KGaA, Thermo Fischer Scientific, Bio-Rad Laboratories, GE Healthcare, Geno Technology, BioTek ...
The basal machinery controlling PCD appears to have been substantially conserved throughout metazoan evolution. The mammalian bcl‐2 gene family encodes cell death regulator proteins that exhibit structural and functional homology with the product of the death‐suppressing ced‐9 gene of C.elegans. Likewise, the ced‐3 killer gene of C.elegans encodes a member of the conserved caspase family of cysteine proteases, members of which play critical proapoptotic roles in mammalian apoptosis.. However, despite this conservation of the basal machinery between the nematode and mammals, neither ced‐9/bcl‐2 nor caspase homologues has yet been identified in the fruit fly, D.melanogaster. Indeed, the proapoptotic machinery so far defined in Drosophila via genetic screening comprises three genes, rpr, hid and grim that share little if any homology with known components of the mammalian death machinery and none at all with the nematode. The only clear link thus far between the apoptotic machinery in ...
In this paper we used a multiparametric approach to analyze extensively the events occurring during apoptotic cell death of thymocytes, and furthermore, we asked whether alterations in mitochondrial structure and function are occurring in early stages of apoptosis. A multiparametric quantitative analysis was performed on normal or apoptotic thymocytes emerging from a few-hour culture performed in culture medium or in the presence of dexamethasone. Simultaneous detection of light scattering properties, integrity of plasma membrane (trypan blue exclusion), chromatin condensation (AO/EB staining of entire cells or PI staining of nuclei), and DNA fragmentation (in situ nick-translation in apoptotic cells) allowed a precise analysis of the preapoptotic and apoptotic stages. Moreover a thorough study of mitochondrial transmembrane potential (delta psi m) assessed following in a time course study the uptake by apoptotic cells of the cationic lipophilic dye DiOC6(3) or the J-aggregate-forming cation ...
Successful wound closure is mainly the result of two cellular processes: migration and proliferation. Apoptosis has also been suggested to play a role in the mechanisms of wound healing. The fast calcium wave (FCW), triggered immediately after a wound is produced, has been proposed to be involved in determining healing responses in epithelia. We have explored the effects of the reversible inhibition of FCW on the apoptotic and proliferative responses of healing bovine corneal endothelial (BCE) cells in culture. The most important findings of this study are that caspase-dependent apoptosis occurs during the healing process, that the amount of apoptosis has a linear dependence on the migrated distance, and that FCW inhibition greatly increases the apoptotic index. We have further been able to establish that FCW plays a role in the control of cell proliferation during BCE wound healing. These results indicate that one of the main roles of the wave is to inhibit an excessive apoptotic response of the
CCAR1; cell division cycle and apoptosis regulator 1; cell division cycle and apoptosis regulator protein 1; CARP 1; CARP1; FLJ10590; death inducer with SAP domain; cell cycle and apoptosis regulatory protein 1; MGC44628; RP11-437A18.1; novel protein similar to vertebrate cell division cycle and apoptosis regulator 1 (CCAR1 ...
Cell apoptosis assay PaTu8988 cell apoptosis was Inhibitors,Modulators,Libraries detected by the Annexin V Apoptosis Detection Kit in accordance on the producers protocol. Briefly, 1 million cells with indicated therapies were stained with FITC Annexin V and PI. Each early and late apoptotic cells had been sorted by fluorescence activated cell sorting. Cell morphologic examination A total of 4 104 PaTu8988 cells were seeded on glass cover slips during the six very well plate and taken care of using the indicated concentration of SAHA for 48 h. Cells were fixed and stained with Wright Giemsa stain. The slides had been photographed using oil microscopy. In vitro tube formation assay or vasculogenic mimicry assay The tumor cell formation of capillary structure in vitro was examined as we previously described.. Cellular immuno fluorescence staining PaTu8988 cells were seeded on glass cover slips in merely six nicely plates and taken care of with described dosage of SAHA for 48 h. Cells about the ...
The development and growth of aneurysms involve the complex events of arterial wall cells remodeling (38). Previous studies have demonstrated that apoptosis is involved in the pathogenesis of aneurysms (6,7). However, the molecular mechanisms underlying the stimulation of apoptosis in the mouse IA model remains unknown.. To investigate the apoptotic events of IA mice model, the present study investigated the mRNA expression of caspases associated with the mitochondrial apoptotic pathway, including caspase-3, −8 and −9. The activation of caspases serves an essential role during the process of apoptosis (39), which may be caused by an extrinsic or intrinsic pathway, which lead to a terminal common pathway (40). Caspase-8 activation is involved in the extrinsic pathway and caspase-9 is involved in the intrinsic pathway. In the mitochondrial pathway, the release of Cyt-c constitutes an apoptotic complex, which subsequently results in the activation of caspase-9. The activation of caspase-8 and ...
The nuoG gene of Mycobacterium tuberculosis (Mtb) has the ability to inhibit host cell apoptosis. This ability is a virulence factor and does not exist in facultative pathogenic and non-pathogenic mycobacterial species. NuoG is part of the NDH-1 complex, and this study addressed the potential link between the role of NuoG in apoptosis inhibition and the biochemical activity of the NDH-1 complex. Different mycobacterial species were tested for their NDH-1 activities. Among the bacteria tested were bacteria transformed with the Mtb nuoG plasmid, or with the almost entire NDH-1 coding region. Surprisingly, the levels of NDH-1 activity did not correlate with apoptosis levels, suggesting a potential independent, novel mechanism by which NuoG inhibits host cell apoptosis. ...
Abstract: PURPOSE: The clinical use of the zoledronic acid has been increasing recently, and especially for the treatment of bone metastases. The synergistic effects of zoledronic acid with other chemotherapeutic agents have been shown. However it is not known whether a similar synergistic apoptotic effects exist for a combination therapy of zoledronic acid with radiation. METHODS: The MCF-7 human breast cancer cell lines were treated with 10 micrometer, 50 micrometer or 100 micrometer of zoledronic acid, irradiated with 5 Gy, and they were also treated with a combination of both treatments. The results of the synergistic effect on apoptosis were identified by performing XTT assay, DNA fragmentation assay, FACS analysis and western blot analysis at 24, 48, 72 hours after treatment. RESULTS: Zoledronic acid afftects anti-proliferative and apoptotic effects on MCF-7 breast cancer cell line in a dose-dependent manner. The synergistic cytotoxic effect of zoledronic acid and radiation was noted. The ...
Apoptotic signaling is altered at many loci in cancer cells. Although many tumors develop resistance to cytochrome c-induced apoptosis, we have discovered that breast cancer cells exhibit a unique hypersensitivity to cytochrome c-induced apoptosis. Interestingly, this sensitivity is not due to changes in core apoptosomal proteins ( 44) but is due to a PHAPI-mediated posttranslational event that enhances the recruitment of caspase-9 to the Apaf-1 CARD. These findings have the potential to affect breast cancer chemotherapy through the development of apoptosome activators or cytochrome c mimetics as shown, in principle, by the fact that malignant mammary epithelial cells could be more easily killed by cytosolic cytochrome c than their normal counterparts.. PHAPI-mediated increase in caspase activation in breast cancer. Whereas many inhibitory signaling pathways converge on the apoptosome, there are very few physiologic/pathologic examples of enhanced apoptosome activation. Our data suggest that ...
Database of proteins involved in apoptosis Apoptosis Video Apoptosis Video (WEHI on YouTube ) The Mechanisms of Apoptosis ... Scholia has a profile for Apoptosis (Q29892216). Apoptosis & cell surface[permanent dead link] Apoptosis & Caspase 3, The ... animation Apoptosis MiniCOPE Dictionary - list of apoptosis terms and acronyms Apoptosis (Programmed Cell Death) - The Virtual ... Molecular Biology and Cell Biology Apoptosis Research Portal Apoptosis Info Apoptosis protocols, articles, news, and recent ...
Apoptosis is the fifth studio album by American death metal band Allegaeon. Produced by the band's longtime producer Dave Otero ... "ALLEGAEON,Apoptosis". Metal Blade Records. Retrieved April 23, 2019. "Allegaeon Chart History: Top Album Sales". Billboard. ... Gill, Kim (April 17, 2019). "ALBUM REVIEW: Allegaeon - Apoptosis". Ghost Cult. Retrieved April 23, 2019. "The 50 Best Metal ...
Apoptosis inducing factor is involved in initiating a caspase-independent pathway of apoptosis (positive intrinsic regulator of ... Apoptosis Parthanatos PDB: 1M6I​; Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer ... Apoptosis inducing factor is a flavoprotein. It also acts as an NADH oxidase. Another AIF function is to regulate the ... Apoptosis Inducing Factor (AIF) is a protein that triggers chromatin condensation and DNA fragmentation in a cell in order to ...
Like any regulated process, apoptosis is subject to either activation or inhibition by a variety of chemical factors. Apoptosis ... Bcl-2 Caspase cIAP1 cIAP2 Inhibitor of apoptosis domain Survivin XIAP Jacobson, Michael; McCarthy, Nicola (2002). Apoptosis. ... Inhibitors of apoptosis are a group of proteins that mainly act on the intrinsic pathway that block programmed cell death, ... The Inhibitors of apoptosis proteins (IAP) are a family of functionally and structurally related proteins that serve as ...
UV-induced apoptosis UV-induced apoptosis is an adequate (physiological) reaction of a cell damaged by UV radiation (UVR) in a ... This may be the result of partial damage to the apoptosis mechanism by UV radiation [1]. If at moderate doses "pure" apoptosis ... The sequence of events that leads to apoptosis is multifaceted and complex. Despite the simple concept of apoptosis, the ... Since apoptosis is a last resort alternative, it takes the initiation of multiple other genes (ING2, p53, or Ras subfamily) ...
The inhibitor of apoptosis domain -- also known as IAP repeat, Baculovirus Inhibitor of apoptosis protein Repeat, or BIR -- is ... Silke J, Vaux DL (May 2001). "Two kinds of BIR-containing protein - inhibitors of apoptosis, or required for mitosis". J. Cell ... Proteins containing BIR are known as inhibitor of apoptosis proteins (IAPs), or BIR-containing proteins (BIRPs or BIRCs), and ... Verhagen AM, Coulson EJ, Vaux DL (2001). "Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs". Genome ...
The mitochondrial apoptosis-induced channel (or MAC), is an early marker of the onset of apoptosis. This ion channel is formed ... Members of the Bcl-2 protein family regulate apoptosis by controlling the formation of MAC: the pro-apoptotic members Bax and/ ... Mitochondrial Apoptosis-induced Channel". Mol. Biol. Cell. 16 (5): 2424-2432. doi:10.1091/mbc.E04-12-1111. PMC 1087246. PMID ... high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast". J. Cell Biol. 155 ...
Overexpression of this gene interfered with MAP3K12 induced apoptosis. Apoptosis-antagonizing transcription factor has been ... "Entrez Gene: AATF apoptosis antagonizing transcription factor". Guo Q, Xie J (Feb 2004). "AATF inhibits aberrant production of ... Modulation during neuronal apoptosis". Molecular and Cellular Neurosciences. 24 (4): 1038-50. doi:10.1016/j.mcn.2003.08.002. ... Burgdorf S, Leister P, Scheidtmann KH (Apr 2004). "TSG101 interacts with apoptosis-antagonizing transcription factor and ...
Frontiers in cell apoptosis research. New York: Nova Science. pp. 153-171. ISBN 9781600214509. Vaux DL (April 2002). "Apoptosis ... Apoptosis is the process of programmed cell death. From its early conceptual beginnings in the 1950s, it has exploded as an ... The word apoptosis is a combination of the prefix 'apo' and the root 'ptosis': 'apo' means 'away', 'off' or 'apart', and ' ... In a signal article published in 1972, John F. Kerr, Andrew H. Wyllie and A. R. Currie, coined the term "apoptosis" in order to ...
The Cas family of proteins are a family of proteins that induce cellular apoptosis and cell proliferation. Apoptosis is a ... there is an inhibition of apoptosis Along with being an inducer of apoptosis, CAS also plays a role in being a checkpoint for ... Cellular+Apoptosis+Susceptibility+Protein at the US National Library of Medicine Medical Subject Headings (MeSH) v t e ( ... The cellular apoptosis susceptibility protein (CAS) is an exportin which in the nucleus is bound to RanGTP. ...
PUMA apoptosis may also be induced independently of p53 activation by other stimuli, such as oncogenic stress growth factor and ... Inhibiting PUMA induced apoptosis may be an interesting target for reducing the side effects of cancer treatments, such as ... Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID) Caspases Cytochrome c ... Fischer SF, Vier J, Kirschnek S, Klos A, Hess S, Ying S, Häcker G (October 2004). "Chlamydia inhibit host cell apoptosis by ...
... pylori-induced apoptosis in human gastric cancer cells mediated via the release of apoptosis-inducing factor from mitochondria ... Apoptosis-inducing factor, mitochondria-associated 3 is a protein that in humans is encoded by the AIFM3 gene. GRCh38: Ensembl ... "Entrez Gene: Apoptosis inducing factor, mitochondria associated 3". Retrieved 2017-10-24. Xie Q, Lin T, Zhang Y, Zheng J, ... induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro". Exp. Cell Res. 318 (8): 944-54. doi: ...
When a cell is tumorous it does not cease to proliferate inhibiting the apoptosis, as a result, in cancerous cells cIAP1 is ... cIAP1 (also named BIRC2) is the abbreviation for a human protein, cellular inhibitor of apoptosis protein-1. It belongs to the ... Doiron K, Labbé K, Korneluk RG, Barker PA, Saleh M, Bertrand MJ (2009). "Cellular inhibitors of apoptosis cIAP1 and cIAP2 are ... Pu Xia; Yanfei Qi (2012). "Cellular Inhibitor of Apoptosis Protein-1 (cIAP1) Plays a Critical Role in β-Cell Survival under ...
It also prevents apoptosis in several ways: it reduces mitochondrial ROS levels, and it prevents apoptosis-causing protein Bax ... and also protects glioma cells against hypoxia-induced apoptosis by decreasing ROS (conferring evasion of apoptosis). TIGAR is ... TIGAR cannot prevent apoptosis via death pathways that are independent from ROS and p53. In some cells, TIGAR expression can ... When MUC-1 activity is removed, levels of TIGAR decline and cells undergo ROS-induced apoptosis. In a type of head and neck ...
... is a protein that in humans is encoded by the CAAP1 gene. Caspase Apoptosis GRCh38: ...
Lei K, Davis RJ (2003). "JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis". Proc. ... 2007). "Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation". ... Apoptosis. 11 (8): 1349-57. doi:10.1007/s10495-006-8266-1. PMID 16830229. S2CID 19085805. Schmelzle T, Mailleux AA, Overholtzer ... which may be important for sensing intracellular damage and triggering apoptosis. Alternatively spliced transcript variants ...
... and AMID during apoptosis in human cells". Apoptosis. 12 (7): 1155-71. doi:10.1007/s10495-007-0061-0. PMID 17347867. S2CID ... Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points ... Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as ... It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite ...
X-linked inhibitor of apoptosis (XIAP) is hypothesized to promote cancer cell survival and growth, the Macrophage inhibitory ... Catz SD, Johnson JL (January 2003). "BCL-2 in prostate cancer: a minireview". Apoptosis. 8 (1): 29-37. doi:10.1023/a: ... Catz SD, Johnson JL (January 2003). "BCL-2 in prostate cancer: a minireview". Apoptosis. 8 (1): 29-37. doi:10.1023/A: ... Zinc inhibits NF-κB pathways, is antiproliferative, and induces apoptosis in abnormal cells. Unfortunately, oral ingestion of ...
Apoptosis causes a dimerization of S19, inducing a conformation change that allows it to bind to the C5a receptor on monocytes ... The main function of a fine me signal is to be released while a cell undergoing apoptosis is still intact in order to attract ... This suggests that the initiation of apoptosis may be coupled with the release of find me signals from the dying cells. As of ... Phagocytes contribute to the "final stages" of cell death by apoptosis. They are often already nearby a dying cell and do not ...
Apoptosis. 19 (5): 871-82. doi:10.1007/s10495-014-0969-0. PMID 24563182. S2CID 14746593. v t e (Articles without InChI source, ... "Clitocine targets Mcl-1 to induce drug-resistant human cancer cell apoptosis in vitro and tumor growth inhibition in vivo". ... effect of clitocine from the mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells by inducing apoptosis". ...
"Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in ... immunodeficient mice". Apoptosis. 12 (4): 685-94. doi:10.1007/s10495-006-0026-8. PMID 17260186. Guo Z, Wagner GJ (1995). " ...
Soldani C, Scovassi AI (2003). "Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update". Apoptosis. 7 (4): 321-8. ...
Biology portal Apoptosis Autophagy database Autophagin Mitophagy Residual body Sub-lethal damage Liddell HG, Scott R, Jone HS ... The second strategy is to inhibit autophagy and thus induce apoptosis. The first strategy has been tested by looking at dose- ... Kang R, Zeh HJ, Lotze MT, Tang D (April 2011). "The Beclin 1 network regulates autophagy and apoptosis". Cell Death and ... Tavassoly I (2015). Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells. ...
Apoptosis. 14 (4): 549-69. doi:10.1007/s10495-009-0324-z. PMID 19221876. S2CID 13058619. Burns, Tony; et al. (2006) Rook's ...
... interacts with p53 and inhibits p53-mediated transactivation but not apoptosis". Apoptosis. 6 (3): 221-34. doi:10.1023/A: ...
Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID) Caspases Cytochrome c ... Armstrong JL, Veal GJ, Redfern CP, Lovat PE (2007). "Role of Noxa in p53-independent fenretinide-induced apoptosis of ... and Noxa has been shown to be involved in p53-mediated apoptosis. Noxa has been shown to interact with: BCL2-like 1, Bcl-2, and ... a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis". Science. 288 (5468): 1053-8. Bibcode: ...
"AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis". Apoptosis. 19 ...
Protease 2A and 3C also induce apoptosis via intrinsic mitochondria mediated apoptosis, which leads to the release of ... 3C proteinase activity in coxsackievirus causes apoptosis in host cells. Both 2A(pro) and 3C(pro) induce caspase-8-mediated by ... Apoptosis. 12 (3): 513-24. doi:10.1007/s10495-006-0013-0. PMID 17195095. Chau DH, Yuan J, Zhang H, Cheung P, Lim T, Liu Z, Sall ... Apoptosis. 12 (3): 513-24. doi:10.1007/s10495-006-0013-0. PMID 17195095. Ramajayam R, Tan KP, Liang PH (October 2011). "Recent ...
... overexpression of TBX15 reduces apoptosis in cancer cells". Apoptosis. 20 (10): 1338-1346. doi:10.1007/s10495-015-1155-8. PMID ... Tbx15 is noteworthy as a potential marker for cancer, with overexpression being correlated to reduced apoptosis in cancer cells ...
The protein hydrolyzes DNA, is not inhibited by actin, and mediates the breakdown of DNA during apoptosis. Alternate ... Boulares AH, Ren T (January 2004). "Mechanism of acetaminophen-induced apoptosis in cultured cells: roles of caspase-3, DNA ... Apoptosis. 3 (2): 89-95. doi:10.1023/A:1009692807692. PMID 14646506. S2CID 2071259. "Entrez Gene: DNASE1L3 deoxyribonuclease I- ... "Correlation between decreased sensitivity of the Daudi lymphoma cells to VP-16-induced apoptosis and deficiency in DNAS1L3 ...
Apoptosis plays a significant role in the immune system.. Abnormal apoptosis. Many factors can play a role in increased or ... Apoptosis pathways. There are two pathways that can initiate apoptosis in a cell: the intrinsic and extrinsic pathways. In the ... Apoptosis - an overview. Apoptosis is the process of controlled cellular "suicide". Whereas in necrosis cells die due to injury ... Apoptosis - a critical but poorly understood physiological process. Apoptosis is a part of the normal development of an ...
... Vidar Beisvåg vidar.beisvag at Thu Mar 4 05:14:50 EST 1999 *Previous message: Source for ...
... which are the executioners of apoptosis, comprise two distinct classes, the initiators and the effectors. Although general ... Molecular mechanisms of caspase regulation during apoptosis Nat Rev Mol Cell Biol. 2004 Nov;5(11):897-907. doi: 10.1038/nrm1496 ... Caspases, which are the executioners of apoptosis, comprise two distinct classes, the initiators and the effectors. Although ... This article reviews these latest advances and describes our present understanding of caspase regulation during apoptosis. ...
6, 1995, page 15). The term apoptosis first (I believe) appeared in 1972, in a paper by Kerr et al. (J.F.R. Kerr, A.H. Wyllie, ... I think all of us working on any aspect of apoptosis should be cogn ... This is with reference to the Research article on apoptosis (R. Lewis, The Scientist, Febr. ... Apoptosis Research. This is with reference to the Research article on apoptosis (R. Lewis, The Scientist, Febr. 6, 1995, page ...
Apoptosis - Reference pathway [ Pathway menu , Organism menu , Pathway entry , Show description , Image file , Help ] Apoptosis ... The onset of apoptosis is controlled by numerous interrelating processes. The extrinsic pathway involves stimulation of ... balance between the pro-apoptotic and anti-apoptotic signals that eventually determines whether cells will undergo apoptosis, ...
cell cycle and apoptosis regulator protein 2. Names. cell division cycle and apoptosis regulator protein 2. deleted in breast ... cell cycle and apoptosis regulator 2provided by HGNC. Primary source. HGNC:HGNC:23360 See related. Ensembl:ENSG00000158941 MIM: ... Cell cycle and apoptosis regulator 2 at the interface between DNA damage response and cell physiology. Magni M, et al. Mutat ... CCAR2 cell cycle and apoptosis regulator 2 [ Homo sapiens (human) ] Gene ID: 57805, updated on 6-Nov-2022 ...
Detects apoptosis earlier in the process than DNA-based assays such as TUNEL; ... Annexin V-FITC Apoptosis Detection Kit was used:. *in staining of LNCaP prostate cancer cells for measuring the G. lucidum ... Detects apoptosis earlier in the process than DNA-based assays such as TUNEL.. *Rapid labeling of cells. Cell staining takes ...
In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers ... however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. ... In vitro and in vivo studies have demonstrated that lung cell apoptosis is associated with lung fibrosis; ... The relationships between apoptosis index (AI) and silica exposure history, soluble Fas (sFas)/membrane-bound Fas (mFas), and ...
Apoptosis and the number of viable ESCC cells were analyzed using flow cytometry and MTT, respectively, after the treatment of ... Curcumin promotes apoptosis of esophageal squamous carcinoma cell lines through inhibition of NF-kappaB signaling pathway]. ... This study was to evaluate whether curcumin could induce apoptosis through inhibition of NF-kappaB signaling pathway in ESCC ... induction of apoptosis and an increase of the sensitivity of ESCC cell lines towards 5-FU. ...
Jurkat Apoptosis Cell Extracts (etoposide) 2043. Toggle Between Dark and Light Modes Filter: *WB ... Western blot analysis of Jurkat Apoptosis Cell Extracts #2043 using Caspase-3 (8G10) Rabbit mAb, #9665.. Show Less Show More ... Apoptosis Cell Extracts (Jurkat Untreated): Total cell extracts from Jurkat cells serve as a negative control. Supplied in SDS ... Apoptosis Cell Extracts (Jurkat + Etoposide): Total cell extracts from Jurkat cells treated with 25 μM etoposide for 5 hours ...
The Apoptosis research has been constantly evolving in recent years and many researchers are working hard to find new ... Apoptosis. Apoptosis, or the process of programmed cell death by which individual cells are eliminated through highly ... The critical involvement of apoptosis within morphogenesis and tissue homeostasis, as well as the absence of normal apoptotic ... activity in cancer cells and some degenerative diseases, signify the importance of research concerning apoptosis and those ...
We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone ... Apoptosis Detection by Annexin V-FITC/PI Staining. FITC annexin V apoptosis detection kit was used to detect apoptosis. Cells ... XIAP, AIF, Bax, and Bcl-2 are apoptosis-related proteins. The level of XIAP, a member of the inhibitors of apoptosis proteins ( ... Extrinsic apoptosis was also reported in HeLa cervical cancer cells by enhancing TRAIL-induced apoptosis and increasing the ...
All the latest science news about cell apoptosis from ... News tagged with cell apoptosis. * Date 6 hours 12 hours 1 day ... Apoptosis is a process that causes cell death. It can go awry in cancer cells, sustaining the disease. Scientists at St. Jude ... Coronaviruses can induce host cell apoptosis. A large team of researchers working at the University of Hong Kong has found that ... The protein tBID can trigger programmed cell death (apoptosis) by inducing damage in the energy suppliers of the cells, the ...
SC Smith, E Price, EM Symonds, PN Baker; Apoptosis in the Human Placenta. Clin Sci (Lond) 1 February 1997; 92 (s36): 19P. doi: ...
Dysregulation of apoptosis causes many diseases including cancers. Transcriptional induction of pro-apoptotic genes is ... In the current study, we identified that Dmp18, the homolog of Znhit1, regulates apoptosis by mediating the histone variant ... Together, this study reveals the mechanism by which Dmp18 regulates apoptosis in the eye and wing discs. ... sufficient to induce apoptosis in Drosophila. Znhit1 encodes a Zinc finger HIT-type containing protein and works as a component ...
Imaging of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD). The safety and scientific validity of this study is the ... Apoptosis, a process of programmed cellular death, correlates with COPD severity and is not seen in the normal adult lung. In ... In this proposal, the investigators aim to assess a molecular imaging probe targeting apoptosis, a cellular process known to be ... The investigators will determine if the imaging signal correlates with serum biomarkers of apoptosis and inflammation. It is ...
... suggesting that apoptosis initiation was likely too weak to initiate downstream apoptosis execution. Indeed, experiments in ... which the mitochondrial apoptosis threshold was lowered by antagonizing Mcl-1 re-established sensitivity to IZI1551+marizomib ... In cases of treatment resistance, lowering the mitochondrial apoptosis threshold appeared sufficient to restore apoptosis ... suggesting that apoptosis initiation was likely too weak to initiate downstream apoptosis execution. Indeed, experiments in ...
Apoptosis has been described in a wide variety of cell and tissue types from nematodes to mammals. Apoptosis, unlike necrosis, ... The genes involved in apoptosis have been defined in animals as well as in plants. Some of these genes act as inducers while ... The possible role of apoptosis may be related to the regulation of normal development as in animals or it may be involved in ... It has been found that apoptosis related genes have high homology in terms of DNA sequences, suggesting the occurence of an ...
Studies of defects in the apoptosis pathway help elucidate biomolecular mechanisms of cancer cells. (Image courtesy of NASA.) ... Diagram of the programmed cell death process known as apoptosis. ... Diagram of the programmed cell death process known as apoptosis ... Diagram of the programmed cell death process known as apoptosis. Studies of defects in the apoptosis pathway help elucidate ... Studies of defects in the apoptosis pathway help elucidate biomolecular mechanisms of cancer cells. (Image courtesy of NASA.) ...
Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G2/M phase, and induced apoptosis in human ... Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal ... The apoptosis was detected using the annexinV:PE apoptosis detection kit and the autophagy was determined using Cyto-ID® Green ... Conversation between apoptosis and autophagy: "Is it your turn or mine?". Apoptosis. 2011;16(4):321-333. ...
One hypothesis (for this difference) is that in a state of disease you tend to see a predominance of late apoptosis in early ... At 3 weeks, the majority of cells were in late apoptosis in the untreated controls, but interestingly there was a reduction in ... PI-positive cells were necrotic, those stained with annexin V were in early apoptosis, and those stained with both markers were ... Three weeks and 8 weeks later, there was a significant reduction in the level of apoptosis in annexin-positive cells, Dr. ...
... and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and ...
Learn more about Apoptosis Intracellular Kinases including related products, articles and interactive pathways. ... Apoptosis Intracellular Kinases. Intracellular signaling pathways regulate the decision of whether a cell lives or dies. While ... Intracellular kinases ultimately activate or inhibit other cellular proteins involved in apoptosis, or transcription factors ... two Bcl-2 family members that protect the cell from apoptosis. ... Apoptosis Catalog 2010 (PDF 5MB) * DuoSet IC (IntraCellular) ...
Selective apoptosis of lung cancer cells with talc. P. Lee, L. Sun, C. K. Lim, S. E. Aw, H. G. Colt ... Selective apoptosis of lung cancer cells with talc Message Subject (Your Name) has sent you a message from European Respiratory ... Apoptosis measurement of lung adenocarcinoma cells with talc (75 μg·mL−1) at 72 h. G0/G1: 52.56% 5: 11.30%; G2/M: 9.94%; ... Differences in the apoptosis rates of LAC were observed with graded concentrations of talc, bleomycin, and doxycycline at 24 h ...
Infection of epithelial cells and lymphocytes has been shown to induce apoptosis in vitro (4-8). Several modes of apoptosis ... lymphocyte apoptosis may not be a direct consequence of infection in these cells. Apoptosis of lymphocytes may have been caused ... virus was also shown to induce lymphopenia and lymphocyte apoptosis in vivo (14). However, whether and to what extent apoptosis ... Infection of primary human lymphocytes in vitro has been shown to induce apoptosis (7). Increased apoptosis leading to severe ...
Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9.. 21. ... Online version: ...
... and a diatom-produced chemical that promotes apoptosis in offspring of a copepod. Mechanisms that serve to depress apoptosis ... Whether apoptosis in crustaceans is mainly transcriptionally regulated as in D. melanogaster (e.g., RHG „killer‟ proteins), or ... Our knowledge about regulation of apoptosis in this phylum is largely based on findings for the fruit fly Drosophila ... We speculate that differences in regulation of the intrinsic pathway of crustacean apoptosis might represent a prerequisite for ...
View mouse Ccar1 Chr10:62579707-62628065 with: sequences, polymorphisms, proteins, references, function, expression
Figure 6. Apoptosis Assays. A) DNA Fragmentation assay. Genomic DNA was prepared from cells (lanes 2, 4, 6, and 8, respectively ... Apoptosis or programmed cell death represents a physiological form of cell death that occurs during development and in the ... Apoptosis was detected using the peroxidase apoTag kit (Appligene Oncor). Fixed cells were pretreated with proteinase K (20 mg/ ... Bortner, C Oldenburg, N Cidlowski, J (1995) The role of DNA fragmentation in apoptosis. Trends Cell Biol 5: 21-26 Breitman ML, ...
Furthermore, anti-NS1-induced endothelial cell apoptosis was NO-dependent, whereas DENV infection-induced apoptosis was ... Increased dengue virus-infected endothelial cell apoptosis caused by antibodies against nonstructural protein 1.. ... Either DENV infection or anti-NS1 treatment caused endothelial cell apoptosis. Importantly, co-treatment with anti-NS1 ... 2007)‎. Increased dengue virus-infected endothelial cell apoptosis caused by antibodies against nonstructural protein 1.. WHO ...
  • Etoposide treatment induces proteolytic cleavage of various apoptosis-related proteins including caspases, IAP, and PARP. (
  • Dysregulation of apoptosis induces a variety of diseases, including cancers, autoimmune diseases, and neurodegenerative diseases [ 3 - 5 ]. (
  • In summary, the mechanism by which Stattic induces apoptosis in MV4-11cells may involve blocking DNA damage repair machineries. (
  • These results suggest that ACE induces apoptosis in AGS gastric cancer cells, and therefore, ACE may have the potential to treat gastric cancer. (
  • In conclusion, sodium fluorosilicate induces apoptosis in HOS cells through decrease in Bcl-2, the release of cytochrome c to the cytosol and activation of caspase-3. (
  • Details] Repetitive exposure to a 60-Hz time-varying magnetic field induces DNA double-strand breaks and apoptosis in human cells [med. (
  • Curcumin inhibits the phosphorylation of IkappaBalpha, leading to suppression of proliferation, induction of apoptosis and an increase of the sensitivity of ESCC cell lines towards 5-FU. (
  • We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. (
  • Inhibition of DNA synthesis, induction of cell cycle arrest in S phase, apoptosis, and cell differentiation were previously reported to be mediated by xanthohumol on MDA-MB-435 human mammary adenocarcinoma cells [ 7 ]. (
  • Transcriptional induction of pro-apoptotic genes is sufficient to induce apoptosis in Drosophila . (
  • Several modes of apoptosis induction and responsible viral genes have been proposed ( 8 - 13 ). (
  • Since peak annexin staining and apoptosis in this model occur at 3 weeks after surgical induction of elevated IOP, this finding indicated that CoQ10 treatment had decreased the level of both early and late apoptosis at an early stage of disease, Dr. Cordeiro said. (
  • Pathway analysis revealed induction of the p53 apoptosis pathway, consistent with apoptosis being the major response to RITA in cancer cells. (
  • Induction of apoptosis by sodium fluorosilicate treatment in human osteogenic sarcoma (HOS) cells. (
  • Induction of apoptosis, such as nucleosomal DNA fragmentation and the appearance of apoptotic bodies, were observed in HOS cells by agarose gel electrophoresis and by flow cytometric analysis, respectively. (
  • The molecular mechanism of apoptosis induction in HOS was investigated by Western blot analysis. (
  • Unlike plated 2D hepatocytes, which are at least partially resistant to apoptosis due to activation of PI3K/Akt pathway (1) , 3D InSight™ Human Liver Microtissues maintain susceptibility towards induction of apoptosis, making it possible to detect early signs of hepatotoxicity with sensitive cell based-assays. (
  • A full induction of apoptosis required the activation of both ROS- and p73-mediated pathways. (
  • In vivo studies in the athymic mice xenograft model also confirmed the growth inhibitory effect and induction of apoptosis by these LOX inhibitors in pancreatic cancer. (
  • Ready-to-use high quality apoptosis inducers allow users an easy tool for induction of apoptosis in cultured cells. (
  • Ces patientes ont été soumises à une induction d'ovulation et ont reçu, sur la base d'une répartition aléatoire et en aveugle, de la silymarine (70 mg × 3 fois par jour) ou un placebo, dès le début du cycle d'induction. (
  • The induction of apoptosis upon infection results from a complex interaction of parasite proteins with cellular host proteins. (
  • However, in some cases, it has been shown that induction of apoptosis in the infected cells significantly imparts protection to the host from the pathogen. (
  • Induction of bucal mucosal apoptosis with chronic alcohol ingestion. (
  • This study was to evaluate whether curcumin could induce apoptosis through inhibition of NF-kappaB signaling pathway in ESCC cells. (
  • Once activated, these caspases cleave and activate downstream effector caspases (including 3, 6 and 7), which in turn cleave cytoskeletal and nuclear proteins like PARP, α-fodrin, DFF and lamin A, and induce apoptosis. (
  • Drug-free macromolecular therapies can induce cell apoptosis by clustering non-internalizing cell-surface receptors. (
  • A large team of researchers working at the University of Hong Kong has found that three major types of coronaviruses are able to induce cell apoptosis in infected hosts. (
  • Infection of epithelial cells and lymphocytes has been shown to induce apoptosis in vitro ( 4 - 8 ). (
  • Infection with virulent influenza (H5N1) virus was also shown to induce lymphopenia and lymphocyte apoptosis in vivo ( 14 ). (
  • Similarly, other intracellular kinases activate transcription factors such as CREB and STAT family members which induce the expression of Bcl-2 and Bcl-x L , two Bcl-2 family members that protect the cell from apoptosis. (
  • Mechanisms of Apoptosis in Crustacea: What Conditions Induce Versus Suppress Cell Death? (
  • Radiotherapy and most chemotherapies induce apoptosis by causing DNA double-strand breaks (DSBs) in tumor cells. (
  • In conclusion, LOX inhibitors block pancreatic cancer cell proliferation and induce apoptosis through the mitochondrial pathway both in vivo and in vitro. (
  • Although amiloride was able to induce apoptosis in myeloma cells lacking p53 expression, activation of p53 signaling was observed in wild-type and mutated TP53 cells after amiloride exposure. (
  • Whereas in necrosis cells die due to injury or disease, apoptosis is a natural part of the regulation and development of the body's biological processes. (
  • Apoptosis, unlike necrosis, is mediated by the active participation of dying cells. (
  • Dr. Cordeiro explained that investigation of what happens before a cell dies has relied on tissue culture studies of staining characteristics to determine whether a cell has gone into early or late apoptosis or necrosis. (
  • At 3 weeks, the majority of cells were in late apoptosis in the untreated controls, but interestingly there was a reduction in the level of late, but not early, apoptosis and in the level of necrosis with treatment. (
  • One hypothesis (for this difference) is that in a state of disease you tend to see a predominance of late apoptosis in early disease, and as the disease progresses there may be less apoptosis and more necrosis,' Dr. Cordeiro said. (
  • Annexin V staining was suppressed in the treated rats, although there was little effect on necrosis and late apoptosis. (
  • As the plasma membrane becomes increasingly permeable during the later stages of apoptosis, 7-AAD can readily move across the cell membrane and bind to cellular DNA, providing a means for identifying those cells that have lost membrane integrity through mechanisms including necrosis. (
  • Tumor necrosis factor receptor superfamily member 6 precursor (FASLG receptor) (Apoptosis-mediating surface antigen FAS) (Apo-1 antigen) (CD95 antigen). (
  • Both apoptosis and necrosis were involved in the pathogenesis of the cochlear lesion, but apoptosis appeared to be the major cell death pathway leading to the styrene ototoxicity. (
  • Apoptosis produces apoptotic bodies, which are cell fragments that are then engulfed by phagocytic cells. (
  • Age-related increases in apoptotic lymphocytes lead to the increased death rate of cells in the bone marrow and the thymus, and this increased rate of apoptosis is one of the significant factors in aging itself. (
  • It is the balance between the pro-apoptotic and anti-apoptotic signals that eventually determines whether cells will undergo apoptosis, survive or proliferate. (
  • Apoptosis Cell Extracts (Jurkat + Etoposide): Total cell extracts from Jurkat cells treated with 25 μM etoposide for 5 hours serve as a positive control for activated apoptotic cascades. (
  • The critical involvement of apoptosis within morphogenesis and tissue homeostasis, as well as the absence of normal apoptotic activity in cancer cells and some degenerative diseases, signify the importance of research concerning apoptosis and those cytokines involved in the activation or suppression of apoptotic events. (
  • We showed that loss of Dmp18 disrupted eye and wing development, up-regulated transcription of pro-apoptotic genes, and induced apoptosis. (
  • These results indicate that Dmp18 negatively regulates apoptosis by mediating H2Av incorporation and histone H3 modifications at pro-apoptotic gene loci for transcriptional regulation. (
  • In the current study, we identified that Dmp18, the homolog of Znhit1, regulates apoptosis by mediating the histone variant H2Av incorporation and H3K4me3 as well as H3K27me3 modifications around the transcription start site (TSS) regions of pro-apoptotic genes. (
  • Intracellular kinases ultimately activate or inhibit other cellular proteins involved in apoptosis, or transcription factors that inhibit the expression of pro-apoptotic proteins, or promote the expression of cell survival proteins. (
  • Pro-apoptotic stimuli described for crustaceans include UV radiation, environmental toxins, and a diatom-produced chemical that promotes apoptosis in offspring of a copepod. (
  • Using pancreatic cancer cell lines with or without expressing mutated K-ras, we demonstrated that the inhibition of endogenous PKC activity sensitized human pancreatic cancer cells (MIA and PANC-1) expressing mutated K-ras to apoptosis, which had no apoptotic effect on BxPC-3 pancreatic cancer cells that contain a normal Ras as well as human lung epithelial BAES-2B cells. (
  • Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining showing numerous apoptotic alveolar epithelial cells in lung of patient B (A) and leukocytes in lung of patient A (B). C) Lung tissue from a patient with pneumonia caused by human influenza A (H5N1) virus showing apoptosis only in leukocytes. (
  • Apoptotic cells (early apoptotic Annexin V+/PI- PF-2341066 cells and past due apoptotic Annexin V+/PI+ cells) had been examined using the Annexin V FITC apoptosis recognition package I (BD) based on the producers suggestions. (
  • Objectives: This study describes the occurrence of apoptosis in periapical cysts with atrophic and hyperplastic epithelium, making a morphologic study quantifying the apoptotic indices and verifying the quantitative differences between them. (
  • In the extrinsic pathway, apoptosis is initiated by external signals from other cells. (
  • The average adult human loses somewhere between 50 to 70 billion cells per day through the process of apoptosis. (
  • Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). (
  • Apoptosis and the number of viable ESCC cells were analyzed using flow cytometry and MTT, respectively, after the treatment of curcumin, 5-FU, or the combination of curcumin and 5-FU. (
  • Apoptosis Cell Extracts (Jurkat Untreated): Total cell extracts from Jurkat cells serve as a negative control. (
  • Apoptosis, or the process of programmed cell death by which individual cells are eliminated through highly controlled fragmentation into membrane-bound particles for phagocytosis by surrounding cells, is employed during normal physiological conditions to produce deliberate and orderly death of cells not destined to be present in the final tissue. (
  • The protein tBID can trigger programmed cell death (apoptosis) by inducing damage in the energy suppliers of the cells, the mitochondria. (
  • Apoptosis is an important biological process in the development and stress context by removing unwanted or damaged cells. (
  • Programmed Cell Death (PCD) or apoptosis plays essential roles both in the development and stress context by removing unwanted or damaged cells to keep the balance [ 1 , 2 ]. (
  • Indeed, experiments in which the mitochondrial apoptosis threshold was lowered by antagonizing Mcl-1 re-established sensitivity to IZI1551+marizomib in otherwise resistant cells. (
  • Programmed cell death, or apoptosis, is the process whereby certain cells are induced to activate their own death or cell suicide. (
  • Studies of defects in the apoptosis pathway help elucidate biomolecular mechanisms of cancer cells. (
  • Apoptosis was observed in alveolar epithelial cells, which is the major target cell type for the viral replication. (
  • Our data suggest that apoptosis may play a major role in the pathogenesis of influenza (H5N1) virus in humans by destroying alveolar epithelial cells. (
  • Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G 2 /M phase, and induced apoptosis in human ESCC Ec109 and KYSE70 cells. (
  • PI-positive cells were necrotic, those stained with annexin V were in early apoptosis, and those stained with both markers were in late apoptosis. (
  • Three weeks and 8 weeks later, there was a significant reduction in the level of apoptosis in annexin-positive cells,' Dr. Cordeiro said. (
  • The objectives of our study were to determine if talc caused apoptosis of lung cancer cells, and to compare talc against other commonly administered intrapleural sclerosing agents by extending the experiments to include bleomycin and doxycyline. (
  • Apoptosis measurement of lung adenocarcinoma cells with talc (75 μg·mL −1 ) at 72 h. (
  • Mechanisms that serve to depress apoptosis include the inhibition of caspase activity by high potassium in energetically healthy cells, alterations in nucleotide abundance during energy-limited states like diapause and anoxia, resistance to opening of the calcium-induced MPTP, and viral accommodation during persistent viral infection. (
  • Apoptosis of pancreatic cancer cells induced by LOX inhibitors (including the nonselective LOX inhibitor nordihydroguaiaretic acid, the 5-LOX inhibitor Rev-5901, and the 12-LOX inhibitor baicalein) was confirmed by growth inhibition, annexin V binding, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay in MiaPaCa-2 and AsPC-1 human pancreatic cancer cells. (
  • No. 10010-09) employs a R-phycoerythrin-conjugated Annexin V (Annexin V-PE) in concert with 7-Aminoactinomycin D (7-AAD) to evaluate subpopulations of cells undergoing apoptosis. (
  • During the early stages of apoptosis, cells begin to display phosphatidylserine (PS) on the outer cell membrane where it is readily detectable by staining the cells with Annexin V-PE. (
  • Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. (
  • Cell proliferation inhibitory and apoptosis-inducing properties of anacardic acid and lunasin in human breast cancer MDA-MB-231 cells. (
  • Additionally, DHM significantly induced the apoptosis of SK-MEL-28 cells, and enhanced the expression levels of Bax proteins and decreased the protein levels of IKK-α, NF-κB (p65) and P-p38. (
  • Dithiothreitol (DTT) effectively suppressed the phenylarsine oxide-inhibited cellular reductive capacity, but unexpectedly, enhanced As 2 O 3 -induced apoptosis in NB4 cells. (
  • As 2 O 3 -induced and As 2 O 3 -plus-DTT-induced apoptosis in NB4 cells was modulated by oxidant modifiers, but not by nitric oxide synthase inhibitors. (
  • The number and quality of oocytes retrieved were evaluated and apoptosis of granolusa cells was studied. (
  • Exosomes released from U87 glioma cells treated with curcumin and/or temozolomide produce apoptosis in naive U87 cells. (
  • Naïve U87 cells were treated with the isolated exosomes , and the effects on apoptosis -related proteins HSP27, HSP70, HSP90, and P53 were assessed. (
  • Moreover all treatment groups increased apoptosis in naïve U87 recipient cells . (
  • DNA-damage, cell cycle arrest and apoptosis induced in BEAS-2B cells by 2-hydroxymetyl methacrylate (HEMA). (
  • CD8+ T cells also contribute to thrombocytopenia by increasing platelet apoptosis. (
  • The present study investigated the effect of miR-29a-3p in glioma exosomes on the proliferation and apoptosis levels of U251 glioma cells under hypoxia. (
  • Furthermore, the effects of miR-29a-3p on proliferation and apoptosis in glioma cells in those processes could be reversed by the PI3K-AKT agonist Recilisib. (
  • Co-cultured HCV+ NK cells and HCV+ DCs showed significantly higher apoptosis of both cells. (
  • In the intrinsic pathway cellular stress, once detected, causes the cell to self-initiate apoptosis. (
  • The Fas pathway (which involves the fas - fast apoptosis signal - receptor, a transmembrane protein) is another initiator for the extrinsic pathway. (
  • Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis. (
  • These results indicate that AM apoptosis could be used as a potential biomarker for human silicosis, and the Fas/FasL pathway may regulate this process. (
  • Curcumin promotes apoptosis of esophageal squamous carcinoma cell lines through inhibition of NF-kappaB signaling pathway]. (
  • It was thought until recently that once a cell started down the pathway toward apoptosis, it was committed to die. (
  • We speculate that differences in regulation of the intrinsic pathway of crustacean apoptosis might represent a prerequisite for some species to survive harsh environmental insults. (
  • Our previous studies have demonstrated that blockade of either the 5-lipoxygenase (LOX) or 12-LOX pathway of arachidonic acid metabolism inhibited pancreatic cancer cell proliferation and induced apoptosis. (
  • Stattic can inhibit the proliferation, promote apoptosis, arrest cell cycle at G0/G1, and suppress DNA damage repair in MV4-11cells. (
  • The aim of the present study was to evaluate the effects of DHM on cell proliferation, cell cycle distribution and apoptosis in the human melanoma SK-MEL-28 cell line, and to explore the related mechanisms. (
  • AK5, a novel prognosis marker, inhibits apoptosis and promotes autophagy as well as proliferation in human gastric cancer. (
  • Detects apoptosis earlier in the process than DNA-based assays such as TUNEL. (
  • PE ® Annexin V Apoptosis Kit for use in flow cytometry assays. (
  • We used a combination of apoptosis assays, cell cycle assays, tissue distribution studies, cell endocytosis, transwell invasion assays, and immunoblotting to evaluate the characteristics of [email protected] as a drug delivery system. (
  • There are two pathways that can initiate apoptosis in a cell: the intrinsic and extrinsic pathways. (
  • Both death receptor and mitochondrial apoptosis pathways were also reported to be activated by xanthohumol. (
  • This poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate. (
  • Characterization of the players, pathways, and their significance in the core machinery of crustacean apoptosis is revealing new insights for the field of cell death. (
  • This review discusses the significance of various pathways/steps during virus-mediated modulation of host cell apoptosis. (
  • Various biological processes such as apoptosis and autophagy are involved in almost every stage of atherosclerosis, which could lead to plaque instability causing stroke and death. (
  • However, the association of FABP4 with macrophage apoptosis and autophagy in atherosclerosis has not been elucidated. (
  • We hypothesize that silencing FABP4 protein could be a novel therapeutic approach to attenuate macrophage apoptosis and autophagy thereby minimizing plaque instability in atherosclerosis. (
  • Abrogation of host cell apoptosis is often beneficial for the pathogen and results in a successful host invasion. (
  • Caspases, which are the executioners of apoptosis, comprise two distinct classes, the initiators and the effectors. (
  • Caspases, a family of cysteine acid proteases, are central regulators of apoptosis. (
  • The inhibitor of apoptosis protein (IAP) family includes XIAP and survivin and functions by binding and inhibiting several caspases (4,5). (
  • Caspases are aspartate-directed cysteine proteases that cleave a diverse group of intracellular substrates to contribute to various manifestations of apoptosis. (
  • CASP3_HUMAN ] Involved in the activation cascade of caspases responsible for apoptosis execution. (
  • Nicholson, Donald W. / Control of Apoptosis by Proteases . (
  • Inhibition of apoptosis suppressed the eye defects caused by Dmp18 deletion. (
  • Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. (
  • The main extrinsic mediator of apoptosis is TNF-alpha, a cytokine that is produced by activated macrophages. (
  • We've also proven that PAI-1 protects EC from Fas ligand (Fas-L)-reliant extrinsic apoptosis [8]. (
  • The presence of CoQ10 significantly reduced the level of the first peak of early apoptosis, suggesting that it could indeed make a difference in the level of apoptosis,' Dr. Cordeiro concluded. (
  • E) Normal spleen tissue showing only a minimal level of apoptosis. (
  • Regulator of calcineurin 1 (RCAN1) facilitates neural apoptosis through caspase-3 activation. (
  • Increased dengue virus-infected endothelial cell apoptosis caused by antibodies against nonstructural protein 1. (
  • Importantly, co-treatment with anti-NS1 antibodies increased DENV-induced endothelial cell apoptosis. (
  • For example, the separation of individual fingers in the fetal stage is due to apoptosis of the cellular material between them. (
  • In this proposal, the investigators aim to assess a molecular imaging probe targeting apoptosis, a cellular process known to be pathogenic in COPD. (
  • Apoptosis, a process of programmed cellular death, correlates with COPD severity and is not seen in the normal adult lung. (
  • Equal numbers of PMC and LAC were exposed to 25, 50 and 75 μg·mL −1 of talc, bleomycin and doxycycline, and cellular apoptosis was measured with propidium iodide staining and flow cytometry at 24, 48 and 72 h. (
  • 14.3.3 proteins are a group of highly conserved proteins that are involved in many vital cellular processes such as metabolism , protein trafficking, signal transduction , apoptosis and cell cycle regulation. (
  • The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. (
  • Xanthohumol (Figure 1 ), a prenylated chalcone isolated from the female hop plant, Humulus lupulus , was reported to have in vitro antiproliferative and apoptosis-inducing properties on prostate, ovarian, breast, and endometrium cancer cell lines [ 5 ]. (
  • RÉSUMÉ Pour étudier les effets de la silymarine sur le développement folliculaire, nous avons recruté 40 femmes en bonne santé subissant une fécondation in vitro (FIV) en raison d'une infertilité masculine. (
  • In the H460 cell line, XIAP (X-linked inhibitor of apoptosis protein) is overexpressed. (
  • This study investigated the underlying mechanisms for LOX inhibitor-induced apoptosis and the potential of LOX inhibitors as antipancreatic cancer agents using the athymic mice xenograft model. (
  • The idea is that in vivo mitochondrial dysfunction occurs before apoptosis,' said Dr. Cordeiro, also head of the Glaucoma and Neurodegenerative Disease Research Group and consultant ophthalmologist at Western Eye Hospital, London. (
  • In addition, apoptosis induced by xanthohumol also involves endoplasmic reticulum stress and unfolded protein response. (
  • Scientists at St. Jude Children's Research Hospital have captured the structure of BAK, a protein that triggers apoptosis. (
  • Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9. (
  • There is a strong correlation between apoptosis and the host protein translation machinery: the pathogen makes all possible efforts to modify this process so as to inhibit cell suicide and ensure that it can survive and, in some cases, establish latent infection. (
  • 14.3.3 proteins are phospho-serine/-threonine binding proteins that have a diverse array of partners including transcription factors, biosynthetic enzymes, cytoskeletal proteins , signaling molecules, apoptosis factors and tumor suppressors. (
  • Pulse modulated 900 MHz radiation inhibits thyroid hormone secretion and stimulates thyroid cell apoptosis. (
  • Several mechanisms of neuronal cell death have been proposed for HD, including excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis. (
  • Here, we demonstrate that the chromatin remodeler Dmp18, the homolog of mammalian Znhit1, plays a crucial role in regulating apoptosis in eye and wing development. (
  • It is most commonly used as an inducer of apoptosis in several mammalian cell types. (
  • The investigators will determine if the imaging signal correlates with serum biomarkers of apoptosis and inflammation. (
  • The genes involved in apoptosis have been defined in animals as well as in plants. (
  • It has been found that apoptosis related genes have high homology in terms of DNA sequences, suggesting the occurence of an evolutionarily preserved common programmed cell death mechanism among multicellular organisms. (
  • As early as 1 week, levels of both early and late apoptosis were significantly different between treated rats and untreated controls. (
  • However, the proportion of total apoptosis in the study group was significantly lower than in the placebo group (P = 0.032). (
  • Our results show that the [email protected] treatment significantly increased cancer cell apoptosis and inhibited cell invasion compared to the control Dox group. (
  • In the past several years the investigators have demonstrated the successful ability of AxV-128/Tc to detect apoptosis in vivo in a preclinical animal model of smoke exposure emphysema model. (
  • Skoltech researchers have identified a set of proteins that are important in the process of apoptosis, or programmed cell death. (
  • RUDN biochemists found out that apoptosis (programmed cell death) can be regulated using the EndoG enzyme. (
  • It is also involved in signaling dangerous problems that warrant apoptosis, or programmed cell death. (
  • Programmed Cell Death (PCD) or apoptosis is a highly conserved biological process and plays essential roles both in the development and stress context. (
  • Diagram of the programmed cell death process known as apoptosis. (
  • There are two currently recognized forms of programmed cell death: apoptosis and necroptosis. (
  • Apoptosis is a regulated physiological process leading to cell death. (
  • Apoptosis is a physiological process for cell death that is critical during aging and development. (
  • Activation of Caspase 3/7 preceded the decline in ATP-content and alpha-GST release into the supernatant, suggesting that caspase 3/7 is a sensitive marker for drug-induced apoptosis. (
  • Apoptosis is essential for maintaining tissue balance. (
  • Apoptosis has been described in a wide variety of cell and tissue types from nematodes to mammals. (
  • 2022) Chromatin remodeler Dmp18 regulates apoptosis by controlling H2Av incorporation in Drosophila imaginal disc development. (
  • Cell cycle and apoptosis regulator 2 at the interface between DNA damage response and cell physiology. (
  • Western blot analysis of Jurkat Apoptosis Cell Extracts #2043 using Caspase-7 Antibody, #9492. (
  • Western blot analysis of Jurkat Apoptosis Cell Extracts #2043 using PARP Antibody #9542 (left), and Cleaved PARP (Asp214) (D64E10) XP ® Rabbit mAb #5625 (right). (
  • Apoptosis has been implicated in the pathogenesis of influenza. (
  • Together, this study reveals the mechanism by which Dmp18 regulates apoptosis in the eye and wing discs. (
  • It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. (
  • It was demonstrated that the mechanism of adipocyte killing was apoptosis and a bystander effect, which is presumably mediated by toxic metabolites of CB1954, could be observed. (
  • Thus, apoptosis has become a key tool in cancer treatment, and the mechanism underlying cancer cell growth has become an important target for cancer cell therapy [ 13 ]. (
  • Apoptosis is a process that causes cell death. (
  • An artists rendering of the cell death process known as apoptosis. (
  • Apoptosis plays a vital role in maintaining the balance between cell death and cell division. (
  • Recent research has shown how disruption of apoptosis occurs in NCI-H460, a type of lung cancer. (
  • In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers, and 13 male healthy volunteers. (
  • The end process of apoptosis is the packaging of cell organelles and proteins into membrane-bound blebs (or chunks), which are then consumed and removed by phagocytes. (
  • Dysregulation of apoptosis causes many diseases including cancers. (
  • Apoptosis induced abnormalities can result in uncontrolled cell division, leading to diseases such as cancer [ 12 ]. (
  • The onset of apoptosis is controlled by numerous interrelating processes. (
  • however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. (