Electric Stimulation: Use of electric potential or currents to elicit biological responses.Apoptosis: 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.Apoptosis Regulatory Proteins: 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.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.Caspase 3: 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.Proto-Oncogene Proteins c-bcl-2: 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.Inhibitor of Apoptosis Proteins: 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.Cells, Cultured: 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.Signal Transduction: 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.Electric Stimulation Therapy: Application of electric current in treatment without the generation of perceptible heat. It includes electric stimulation of nerves or muscles, passage of current into the body, or use of interrupted current of low intensity to raise the threshold of the skin to pain.DNA Fragmentation: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Enzyme Activation: 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.Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.In Situ Nick-End Labeling: 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.bcl-2-Associated X Protein: 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.Cell Survival: 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.X-Linked Inhibitor of Apoptosis 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Deep Brain Stimulation: Therapy for MOVEMENT DISORDERS, especially PARKINSON DISEASE, that applies electricity via stereotactic implantation of ELECTRODES in specific areas of the BRAIN such as the THALAMUS. The electrodes are attached to a neurostimulator placed subcutaneously.Physical Stimulation: Act of eliciting a response from a person or organism through physical contact.Apoptosis Inducing Factor: 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.CASP8 and FADD-Like Apoptosis Regulating Protein: 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.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Caspase 9: 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.Tumor Cells, Cultured: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mitochondria: 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)Caspase 8: 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.Fas Ligand Protein: 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.Transcranial Magnetic Stimulation: A technique that involves the use of electrical coils on the head to generate a brief magnetic field which reaches the CEREBRAL CORTEX. It is coupled with ELECTROMYOGRAPHY response detection to assess cortical excitability by the threshold required to induce MOTOR EVOKED POTENTIALS. This method is also used for BRAIN MAPPING, to study NEUROPHYSIOLOGY, and as a substitute for ELECTROCONVULSIVE THERAPY for treating DEPRESSION. Induction of SEIZURES limits its clinical usage.Tumor Suppressor Protein p53: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Blotting, Western: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cytochromes c: 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.Flow Cytometry: 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.bcl-X Protein: 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.Proto-Oncogene Proteins: 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.RNA, Messenger: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Transfection: 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.Rats, Sprague-Dawley: 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.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Mice, Inbred C57BLCell Cycle: 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.Tumor Necrosis Factor-alpha: 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.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Down-Regulation: 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.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Gene Expression Regulation: 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.Up-Regulation: 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.Reactive Oxygen Species: 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.Poly(ADP-ribose) Polymerases: 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.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.RNA, Small Interfering: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Mice, Knockout: 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.NF-kappa B: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.TNF-Related Apoptosis-Inducing Ligand: 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.Neurons: 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.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Proto-Oncogene Proteins c-akt: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Caspase 7: 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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Mitogen-Activated Protein Kinases: 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).Molecular Sequence Data: 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.Membrane Potential, Mitochondrial: 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.T-Lymphocytes: 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.HL-60 Cells: 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)Kinetics: The rate dynamics in chemical or physical systems.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Transcutaneous Electric Nerve Stimulation: The use of specifically placed small electrodes to deliver electrical impulses across the SKIN to relieve PAIN. It is used less frequently to produce ANESTHESIA.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Genes, bcl-2: 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.Staurosporine: 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)DNA-Binding Proteins: 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.Models, Biological: 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.Membrane Proteins: 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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Necrosis: 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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cytochrome c Group: 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)Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)bcl-2 Homologous Antagonist-Killer Protein: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.HeLa Cells: 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.Myeloid Cell Leukemia Sequence 1 Protein: 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.Protein Binding: 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.DNA Damage: 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.Epithelial Cells: 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.Phosphatidylinositol 3-Kinases: 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.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Cell Nucleus: 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)Intracellular Signaling Peptides and Proteins: 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.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Proteins: 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.Mutation: 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.Neoplasm Proteins: 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.Ceramides: 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.p38 Mitogen-Activated Protein Kinases: 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.Disease Models, Animal: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.RNA Interference: 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.Mice, Inbred BALB COxidative Stress: 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).bcl-Associated Death Protein: 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.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Photic Stimulation: Investigative technique commonly used during ELECTROENCEPHALOGRAPHY in which a series of bright light flashes or visual patterns are used to elicit brain activity.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Electrodes, Implanted: Surgically placed electric conductors through which ELECTRIC STIMULATION is delivered to or electrical activity is recorded from a specific point inside the body.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Amino Acid Sequence: 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.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Immunoblotting: 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.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Receptors, TNF-Related Apoptosis-Inducing Ligand: 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.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Cysteine Endopeptidases: 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.Acoustic Stimulation: Use of sound to elicit a response in the nervous system.Fas-Associated Death Domain Protein: 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.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Caspase 2: 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.Hydrogen Peroxide: 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.Macrophages: 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.)Microscopy, Fluorescence: 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.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.MAP Kinase Signaling System: 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.Nuclear Proteins: 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.DNA: 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).U937 Cells: 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.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Mice, Nude: 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.Protein Transport: 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.Oligopeptides: Peptides composed of between two and twelve amino acids.Evoked Potentials: Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Apoptotic Protease-Activating Factor 1: 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.Adaptor Proteins, Signal Transducing: 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 enzymesIsoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Caspase 1: 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.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Recombinant Fusion Proteins: 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.Cell Line, Transformed: 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.Evoked Potentials, Motor: The electrical response evoked in a muscle or motor nerve by electrical or magnetic stimulation. Common methods of stimulation are by transcranial electrical and TRANSCRANIAL MAGNETIC STIMULATION. It is often used for monitoring during neurosurgery.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Lymphocytes: 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.Culture Media, Serum-Free: 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.Animals, Newborn: Refers to animals in the period of time just after birth.Cyclin-Dependent Kinase Inhibitor p21: 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.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Tumor Suppressor Proteins: 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.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Protein Synthesis Inhibitors: 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.DNA Primers: 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.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Extracellular Signal-Regulated MAP Kinases: 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.Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Cell Cycle Proteins: 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.MAP Kinase Kinase Kinase 5: 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.Xenograft Model Antitumor Assays: 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.Afferent Pathways: Nerve structures through which impulses are conducted from a peripheral part toward a nerve center.Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes.Etoposide: 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.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Motor Cortex: Area of the FRONTAL LOBE concerned with primary motor control located in the dorsal PRECENTRAL GYRUS immediately anterior to the central sulcus. It is comprised of three areas: the primary motor cortex located on the anterior paracentral lobule on the medial surface of the brain; the premotor cortex located anterior to the primary motor cortex; and the supplementary motor area located on the midline surface of the hemisphere anterior to the primary motor cortex.Subthalamic Nucleus: Lens-shaped structure on the inner aspect of the INTERNAL CAPSULE. The SUBTHALAMIC NUCLEUS and pathways traversing this region are concerned with the integration of somatic motor function.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
A soluble factor(s) generated by antigen or phytohemagglutinin stimulation of leishmania-specific CD4+ helper T cells from skin ... Antigen-activated T cells produce IL-2 which then acts on IL-2 receptors on regulatory T cells alerting them to the fact that ... Regulatory T cells can produce Granzyme B, which in turn can induce apoptosis of effector cells. Regulatory T cells from ... This is a negative feedback loop to ensure that overreaction is not occurring. If an actual infection is present other ...
... tumor necrosis factor-related apoptosis-inducing ligand) have been shown to induce DISC-mediated apoptosis. Specifically, TRAIL ... It is thought that c-FLIP may be involved in modulating the immune system, as c-FLIPS is upregulated upon stimulation of the T ... Interestingly, humans have a homolog for v-FLIP known as c-FLIP, which occurs in two endogenous forms (c-FLIPL (long) and c- ... In order to do this, downstream targets such as FLICE must be activated. In its inactive state, FLICE's two death domains are ...
Apoptosis can also be triggered by binding of a ligand to tumor necrosis factor receptor 1 (TNFR1); however, the mechanism by ... autocatalytic cleavage occurs at an aspartate residue within their own structures, resulting in an activated protein. This ... However, it is required for B cell proliferation induced by stimulation of TLR3 and TLR4. Activation of nuclear factor kappa B ... Taxol can also cause apoptosis of cells and this requires procaspase 10, which is activated by recruitment to FADD. It has been ...
This means that proper signalling cannot occur, thus apoptosis cannot activate. They may also have defects in the downstream ... Cancer cells do not need stimulation from external signals (in the form of growth factors) to multiply. Typically, cells of the ... mutations that are not inherited but occur after conception). This occurs in a series of steps, which Hanahan and Weinberg ... Apoptosis is a form of programmed cell death (cell suicide), the mechanism by which cells are programmed to die in the event ...
These receptors belong to the nuclear receptor family of ligand-activated transcription factors. To bind their receptors, these ... Hormones occur in multicellular organisms (plants, animals, fungi, brown algae and red algae). These compounds occur also in ... Hormones have the following effects on the body: stimulation or inhibition of growth wake-sleep cycle and other circadian ... rhythms mood swings induction or suppression of apoptosis (programmed cell death) activation or inhibition of the immune system ...
Regulation occurs through NFAT (nuclear factor of activated T-cells) activation, which, when dephosphorylated, binds to GATA ... a potent apoptotic stimulation factor. This is not the primary mechanism of action for clinical use, but is also an important ... effect for research on apoptosis. Ciclosporin binds to the cyclophilin D protein (CypD) that constitutes part of the ... Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NFATc), which moves to the ...
... has been found to act in signaling information after epidermal growth factor(EGF) stimulation. Activated tyrosine kinase ... Oxidative stress occurs when the production of reactive oxygen species (ROS) is greater than their catabolism. ROS production ... SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells. SCOP classifies the ... After the EGF stimulation SHC1 binds to groups of proteins that activate survival pathways. This activation is followed by a ...
The prolongation of coagulation (or prothrombin time, PT) occurs following either tissue factor or contact-phase stimulation ... rate of apoptosis, inflammatory genes expression (especially TNF-α) and protein synthesis, all events which normally occur ... and prolonging activated partial thromboplastin time (aPTT). Prolonged time for lysis further displays the anti-fibrinolytic ... but they are 100,000 times better at inhibiting factor Xa and factor Xia. These inhibitory properties as well as their ...
... or down-regulate intracellular processes such as transcription factor activation and gene regulation resulting in apoptosis or ... When an integrin receptor binds to its ECM ligand and is activated, additional integrins cluster around the activated site. In ... The stimulation of a mechanoreceptor causes mechanically sensitive ion channels to open and produce a transduction current that ... Some intracellular processes that have been observed to occur within these pathways include phosphorylation of ERK1/2, p38 MAPK ...
... tumor necrosis factor-α, vitamin D, retinoic acid, IGF-1, and stimuli such as chemotherapy that activate the tumor suppressor ... This can occur either by enhancing IGF-stimulated proliferation or in the absence of IGF-1. In endothelial cells and mammary ... to IGF-1 stimulation is suppressed by secreted IGFBP-3 and restored when IGFBP-3 is downregulated by epidermal growth factor. ... factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in ...
White blood cells The G-CSF-receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF ... The pharmaceutical analogs of naturally occurring G-CSF are called filgrastim and lenograstim. G-CSF also stimulates the ... and Ras/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal ... to increase the neuroplasticity and to counteract apoptosis. These properties are currently under investigations for the ...
4,5) CD134 is predominantly found on activated T cells and binds to OX40 ligand, causing T-cell stimulation, proliferation, ... Risk factors for infection are being of the male sex, adulthood, and outdoor access. One case study conducted in São Paulo ... False positives occur when the cat carries the antibody (which is harmless) but does not carry the actual virus. The most ... activation, and apoptosis (3). This leads to a significant drop in cells which have critical roles in the immune system. Low ...
... and p38 mitogen-activated protein kinase (p38 MAPK). Activation of the IRAK/MAPK pathway leads to the stimulation of the ... Neiman, J. (Oct 1998). "Alcohol as a risk factor for brain damage: neurologic aspects". Alcohol Clin Exp Res. 22 (7 Suppl): ... During adolescence critical stages of neurodevelopment occur, including remodeling and functional changes in synaptic ... yet other studies have found alcohol-induced NO production to lead to apoptosis (see Neuroinflammation section). Lang, I.; ...
The kinase is activated by insulin and growth factors via phosphatidylinositide-3-kinase, phosphoinositide-dependent kinase ... This occurs as the entrance of Na+ depolarizes the cell, thus allowing the parallel entrance of Cl−. SGK1 has also been shown ... "Thus SGK1 is either not a crucial element in the regulation of cell proliferation or apoptosis, or related kinase(s) can ... However, the functional significance of SGK1 in cell volume regulation, along with its stimulation of cation channels, is still ...
When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including ... Chromatin relaxation occurs rapidly at the site of a DNA damage. In one of the earliest steps, the stress-activated protein ... DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 10,000 to ... are among known stimulation signals for a global response to DNA damage. The global response to damage is an act directed ...
It occurs during lymphocyte development in the thymus and bone marrow for T and B lymphocytes, respectively. In these tissues, ... Since the B cells can only be fully activated after confirmation by more self-restricted T cells that recognize the same ... Those lymphocytes that have receptors that bind strongly to self-antigens are removed by induction of apoptosis of the ... Later in 2003, experiments showed that Treg cells were characterized by the expression of the Foxp3 transcription factor, which ...
Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms. Biochemical events lead to ... Necrosis is cell death caused by external factors such as trauma or infection, and occurs in several different forms. Recently ... It occurs as a result of repeated stimulation of specific T-cell receptors (TCR) and it helps to maintain the periphery immune ... Autophagy is generally activated by conditions of nutrient deprivation but has also been associated with physiological as well ...
It occurs during lymphocyte development in the thymus and bone marrow for T and B lymphocytes, respectively. In these ... Ramsay, AG (2013). ". Immune checkpoint blockade immunotherapy to activate anti-tumour T-cell immunity". Br J Haematol. 162 (3 ... Cytokine absorption leading to cytokine deprivation-mediated apoptosis. nTreg cells and iTreg cells, however, have a few ... Later in 2003, experiments showed that Treg cells were characterized by the expression of the Foxp3 transcription factor, which ...
... leading to a neuronal cell death pathway known as apoptosis. Apoptosis occurs primarily via the increased intracellular ... including activating and inactivating certain K+ channels. Epinephrine is found in the lateral tegmental system, medulla, ... Diagnosis of the disease often stems from clinical observation as well as analysis of family history and other risk factors, ... the probability that the single stimulation of an excitatory synapse will raise the membrane potential past threshold and ...
... protein pathway activated by receptors of growth factors and cytokines. The essence of this transmission consists in direct ... As cells leave the S phase and enter the G2 phase, a massive tyrosine phosphorylation of p34cdc2 occurs. Regulation with ... Tyrosine phosphorylation of certain target proteins is required for ligand stimulation of their enzymatic activity. In response ... T-cells from HIV-infected individuals also display activation defects, and undergo spontaneous apoptosis in culture. ...
Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as ... PPIA may also activate Akt and NF-κB signaling, resulting in the upregulation of Bcl-2, an antiapoptotic protein, and thus ... In the case of T cells, PPIA regulates the T-cell-specific tyrosine kinase ITK upon T-cell receptor stimulation. The PPIA ... a proapoptotic factor, in neurons. To maintain the integrity of the blood brain barrier and mitigate brain injury, PPIA helps ...
In addition, drugs may be developed that activate autocrine signaling in cancer cells that would not otherwise occur. For ... apoptosis has been shown to enhance apoptosis caused by chemotherapeutic drugs through autocrine-secreted tumor necrosis factor ... The cell then releases IL-2, which binds to its own new IL-2 receptors, causing self-stimulation and ultimately a monoclonal ... Another example occurs in activated T cell lymphocytes, i.e., when a T cell is induced to mature by binding to a peptide:MHC ...
... so modulation occurs at the level of protein expression and posttranslational modification. Nerve growth factor IB binds as a ... Liu S, Wu Q, Ye XF, Cai JH, Huang ZW, Su WJ (2002). "Induction of apoptosis by TPA and VP-16 is through translocation of TR3". ... They are immediate early genes activated in a ligand-independent manner that bind at the same sites on response elements. NGFIB ... Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. ...
Increased ATM activity also occurs in viral infection where ATM is activated early during dengue virus infection as part of ... These adaptor proteins then recruit different factors including the effector protein kinase CHK2 and the tumor suppressor p53. ... and the subsequent stimulation of kinase activity with the NBS1 C-terminus. The three domains FAT, PRD and FATC are all ... DNA repair or apoptosis. Several of these targets, including p53, CHK2, BRCA1, NBS1 and H2AX are tumor suppressors. An earlier ...
The transcription factor NF-κB regulates various genes that play essential roles in signaling, stress responses, cell growth ... On the other hand, the oscillatory potential and stabilization of NF-κB during long stimulations has been shown to be reduced ... The Shh signalling is activated independently of GREM1 and AER-FGFs. Propagation phase involves the control of distal ... successful production of mRNA transcripts occurs and the proteins PER and CRY are synthesized. PER and CRY then dimerize and ...
To further test the role of activated androgen receptors on AHN, flutamide, an antiandrogen drug that competes with ... Conversion of testosterone to the more potent DHT occurs the prostate gland, liver, brain and skin. ... with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors". ... this is a measure of epithelial cell function stimulation). Whereas DHT was equally potent as testosterone at preventing ...
May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed: ... 10426996). Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol- ... Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor ... but also partially via TLR4 (PubMed:16622205). MAPK activation in response to bacterial peptidoglycan also occurs via this ...
A single activating mutation (c.1799 T,A; p.V 600 E) in the gene encoding the serine/threonine kinase B-RAF occurs in ,60% of ... B-RAF knockdown by stimulation with growth factors. Ectopic expression of short hairpin RNAs specifically suppressing (V 600 E) ... Growth factors rescue cutaneous melanoma cells from apoptosis induced by knockdown of mutated (V 600 E) B-RAF.. Christensen C1 ... basic fibroblast growth factor but underwent apoptosis or senescence-like growth arrest upon withdrawal of this growth factor. ...
Cirrhosis, viral hepatitis, and toxic drug effects can all trigger apoptosis in the liver as a ... The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known to influence apoptosis, conceivably by ... pathway comprises a major physiological mechanism by which this occurs. The susceptibility to Fas-mediated apoptosis is, in ... present evidence demonstrating that AhR expression and function promote apoptosis in liver cells in response to Fas stimulation ...
Additional assays of apoptosis included Annexin V/propidium iodide staining for the percentage of sub-G0-G1 phase cells as in ... 4C, this significant BAFF protein up-regulation occurred as early as 8 hours after multiple myeloma adhesion to BMSCs, which ... Phosphorylation of AKT and IκBα was observed 5 minutes following BAFF stimulation and sustained until 40 minutes; in contrast, ... Recent studies have underscored the role of B-cell-activating factor (BAFF), a member of the tumor necrosis factor superfamily ...
Neuronal apoptosis usually occurs in EBI after SAH (Figure 1) . P2X7R stimulation activates p38 mitogen-activated protein ... Recombinant milk fat globule-EGF factor-8 reduces oxidative stress via integrin beta3/nuclear factor erythroid 2-related factor ... IMPACT FACTOR 2017: 0.833. 5-year IMPACT FACTOR: 1.247. CiteScore 2017: 1.00. SCImago Journal Rank (SJR) 2017: 0.428. Source ... P2X7 receptor antagonism inhibits p38 mitogen-activated protein kinase activation and ameliorates neuronal apoptosis after ...
The transcription factor NF-κB is also activated in response to oncogenic Ras (6), and this regulation occurs largely through ... of the 3x-κB-dependent reporter in response to the expression of oncogenic Ras or tumor necrosis factor stimulation (14). ... 3A). Although E1A induces apoptosis in a p53-dependent manner (22), our data indicate that E1A can also induce apoptosis in a ... and activation of this transcription factor provides protection against apoptosis (8, 9). Because NF-κB may play a direct role ...
We asked whether paracrine stimulation of prostate epithelium by OSM, which occurs in prostate cancer, affects AR activity. The ... After receptor activation and oligomerization, the Jak/STAT and the MAPK pathways become activated. Subsequently, STAT factors ... The AR3 plays a central role in the regulation of proliferation, differentiation, and apoptosis of prostate cancer cells. The ... keratinocyte growth factor, and epidermal growth factor. Cancer Res., 54: 5474-5478, 1994. ...
A soluble factor(s) generated by antigen or phytohemagglutinin stimulation of leishmania-specific CD4+ helper T cells from skin ... Antigen-activated T cells produce IL-2 which then acts on IL-2 receptors on regulatory T cells alerting them to the fact that ... Regulatory T cells can produce Granzyme B, which in turn can induce apoptosis of effector cells. Regulatory T cells from ... This is a negative feedback loop to ensure that overreaction is not occurring. If an actual infection is present other ...
... brain-derived nerve growth factor (BDNF) regulates neural activity, enhances synaptic activity, and activates dendritic protein ... Several events occur during LTP induction and consolidation, including dendritic protein synthesis and calpain activation. The ... calcium-dependent proteases, calpains, participate in many different signaling pathways, including apoptosis and synaptic ... Mechanisms underlying BDNF stimulation of MTOR-dependent protein synthesis. Page 1. Save page Remove page Previous. 1 of 127. ...
The nuclear factor of activated T-cell (NFAT) family of transcription factors is composed of four calcium-responsive proteins ( ... Pressure stimulation of BMSCs during BOO is different compared with normal conditions. The majority of BOOs involve chronic and ... Li R, Zhang L, Shi W, Zhang B, Liang X, Liu S and Wang W: NFAT2 mediates high glucose-induced glomerular podocyte apoptosis ... Bosch R, Abrams P, Averbeck MA, Finazzi Agró E, Gammie A, Marcelissen T and Solomon E: Do functional changes occur in the ...
... transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogen-activated cells. J Exp Med. ... Suboptimal antigen stimulation, such as occurs with poorly cross-linking soluble autoantigens, can induce tolerogenic signaling ... and transcription factors, including nuclear factor-κB (NF-κB) and nuclear factor of activated T cells (NFAT). The balance of ... On the contrary, stimulation with sol-IgM down-regulated Mcl-1, induced apoptosis, and augmented chemotherapy-induced apoptosis ...
Background Cardiomyocyte apoptosis is a common pathological manifestation that occurs in several heart diseases. This study ... found that under oxidative stress stimulation, apoptosis of cardiomyocytes and p53 up-regulation occurred together . Raut ... was one of the important factors independent of mitochondrial apoptosis that could activate caspase-3 to induce apoptosis [20 ... tp53-induced glycolysis and apoptosis-regulator(TIGAR), and other factors to further activate the death signal receptor pathway ...
MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ... In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480 ... There is growing evidence that activating transcription factor 3 (ATF3) is linked to cell growth arrest and apoptosis in ... Time-course experiment showed that induction of ATF3 by MRBE occurred after 1 h stimulation (Figure 4D).We also evaluated ...
... in two mouse models has been reported to have activated NF-κB and Jun N-terminal kinase (JNK) transcription factors . ... Uprising of tumor necrosis factor-alpha (TNF-α) in fetal liver and brain-induced fetal death occurs through either maternal ... it stimulates transcription factors and mediates various cellular functions including cell differentiation, apoptosis, lipid ... Importantly, stimulation of Nrf2 signals plays a crucial role in ameliorating pregnancy insults. It was further counted that ...
... tumor necrosis factor-related apoptosis-inducing ligand) have been shown to induce DISC-mediated apoptosis. Specifically, TRAIL ... It is thought that c-FLIP may be involved in modulating the immune system, as c-FLIPS is upregulated upon stimulation of the T ... Interestingly, humans have a homolog for v-FLIP known as c-FLIP, which occurs in two endogenous forms (c-FLIPL (long) and c- ... In order to do this, downstream targets such as FLICE must be activated. In its inactive state, FLICEs two death domains are ...
... which protects myocytes against the Gs-mediated apoptosis via activating the survival factor, Akt. ... β1-AR stimulation robustly and consistently increases cardiac myocyte apoptosis. In fact, chronic stimulation of these β-AR ... recent evidence demonstrates that Akt-mediated antiapoptotic effect occurs at the level of cytochrome c, upstream of caspase 9 ... Stimulation of β1-AR but Not β2-AR Induces Myocyte Apoptosis.. β1-AR-induced cardiac cell loss described above might be ...
c-myc is a transcriptional factor for control of cell proliferation, and high expression of c-myc has been found in leukemia ( ... Anti-CD3 stimulation induced high FasL expression, but the presence of chloramphenicol significantly inhibited its expression. ... we examined what would occur in the presence of chloramphenicol. We found that splenocytes stimulated with anti-CD3 in the ... Previously activated T cells will undergo apoptosis after reactivation. This apoptosis, however, can be significantly inhibited ...
... modulation of which using either biological or small chemical agents could contribute to suppression of excessive activated ... was a lymphocyte-activating factor and Interleukin-2 was a T-cell growth factor, thymocyte-stimulating factor, and costimulator ... For both pathways, IL-6 stimulation activates Janus family tyrosine kinases (JAKs), which are associated with gp130 IL6 ... Beside acting as T-lymphocyte growth factor, it has been found that IL-2 takes part in the activation of apoptosis and the ...
We analyzed the effects of signaling molecules, such as innate immunity messengers, transcription factors, LPS, cytokine, ... nuclear factor (NF), κ-light-chain enhancer of activated B cells-κB (NF-κB), and mitogen-activated protein kinase (MAPK) ... LPS can induce apoptosis. Cx43 is increased after LPS stimulation. Through GJs, the apoptosis signals can be transmitted to ... H. K. Eltzschig, T. Eckle, A. Mager et al., "ATP release from activated neutrophils occurs via connexin 43 and modulates ...
2-like proteins whose members inhibit apoptosis or activation of pro-inflammatory transcription factors, such as interferon (I ... protein N1 is an intracellular virulence factor and belongs to a family of VACV B-cell lymphoma (Bcl)- ... Year: 2002Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis.Mol ... activation following TNF stimulation, whereas an inhibitor acting at the TNF receptor complex might do so. ...
Thus, the major process of thymic atrophy in this study first involved activation of transcriptional factors FOS/JUN upon LPS ... binding to TLR4 that caused release of inflammatory factors, thereby inducing inflammatory responses and DNA damage and ... maximum thymocyte death and thymic atrophy occurred at 36 and 72 h, respectively. No significant changes of thymic structure, ... We also found that some anti-inflammatory factors, including BPI, PPARγ and SOCS3, were activated after LPS stimulation. BPI ...
The modifications to this protocol have to be such that they do not activate caspase-1 by itself. If this occurs, a dose ... Masumoto, J., et al. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. J ... This stimulation upregulates NLRP3 and pro-IL-1β through NF-kB signaling. Priming additionally licenses NLRP3 through non- ... The second signal for NLRP3 activation is thought to involve mitochondrial factors, reactive oxygen species, potassium efflux ...
We then focused particularly on genes involved in the regulation of the cytoskeleton, one of the processes occurring during ... apoptosis, lipidogenesis, protein conformation, transport and cell cycle. ... stimulation of growth regulatory pathways, mitogen-activated protein kinase, extracellular signal-regulated kinase and p38 ... An interference with the cytokine TGF-β1 (transforming growth factor-β1)  or with TNF-α (tumor necrosis factor-α) has been ...
... may also occur in end-stage failing hearts.26 80 Apoptosis most likely occurs as a response to prolonged growth stimulation in ... Tumor necrosis factor α and tumor necrosis factor receptors in the failing human heart. Circulation. 1996;93:704-711. ... signals that are activated or induced in the failing human heart can predispose to both necrosis and apoptosis. ... Cardiac myocyte loss may occur via two general mechanisms: necrosis77 and apoptosis (Fig 2⇓).26 79 Necrosis occurs via ...
Transforming growth factor 1 activating kinase (TAK1) is an apical kinase governing activation of both of these pathways. It is ... RIP1 and RIP3 are essential for execution of cell death when apoptosis or inflammatory cascades are inhibited, which occurs ... pivotal in regulating activation of Receptor-interacting protein (RIP) kinase 1 following stimulation of TNFR1, as inhibition ... RIP1, when activated through TNFR1 under appropriate circumstances, recruits caspase-8 and triggers apoptosis (Guo et al., 2016 ...
RegulatesReceptorsDifferentiationNecrosisOxidative stressInhibition of apoptosisActivationInhibitorDemonstrated to undergo apoptosisFamily of cysteine proteasesLigandTransformationImmune systemPI3KProliferation and hinderingGeneInductionEffectorCaspase-9 activatesMechanismsInflammationExogenousCells from apoptosisRegulationAntigenStimulatesPromote apoptosisCaspasesUnderwent apoptosisTranscriptionalCardiomyocyte apoptosisRepressionPeripheral blood lymphUndergoMechanism
- BAFF also attenuates tumor cell apoptosis because exposure of non-Hodgkin's lymphoma (NHL) B cells to recombinant BAFF increases nuclear factor-κB (NF-κB) activation, up-regulates Bcl-2 and Bcl-x(L), and down-regulates Bax ( 17 ). (aacrjournals.org)
- Many studies have shown that the neurotrophic factor, brain-derived nerve growth factor (BDNF) regulates neural activity, enhances synaptic activity, and activates dendritic protein synthesis. (usc.edu)
- Thus, regulation of FasL expression itself, for example, by the transcription factors nuclear factor kappa B (NF-κB), activating protein 1 (AP1), or nuclear factor of activated T cells (NF-AT), regulates FasL/Fas-mediated effects, such as those of activation-induced cell death of CD4 + T cells ( 5 ). (sciencemag.org)
- IL6 regulates tumor proliferation and inhibits apoptosis. (sigmaaldrich.com)
- On T lymphocytes, CXCR4 regulates thymocyte development ( 1 ), apoptosis ( 2 , 3 ), and HIV-1 infection ( 2 ). (jimmunol.org)
- Thus, MKK7 is an essential and specific regulator of stress-induced SAPK/JNK activation in mast cells and MKK7 negatively regulates growth factor and antigen receptor-driven proliferation in hematopoietic cells. (pubmedcentralcanada.ca)
- The death-inducing signaling complex or DISC is a multi-protein complex formed by members of the "death receptor" family of apoptosis-inducing cellular receptors. (wikipedia.org)
- Thus, stimulation of a single class of receptors, β 2 -ARs, elicits concurrent apoptotic and survival signals in cardiac myocytes. (pnas.org)
- The innate immune system uses pattern recognition receptors (PRRs) to recognize non-self material based on factors such as nucleotide sequence specificity and cellular localization ( 2 ). (asm.org)
- Viral infections are sensed by pattern recognition receptors that activate the innate immune system which precedes the development of an adaptive immune response. (prolekare.cz)
- The greatest change in mononuclear cell gene expression occurred at 6 h (439 induced and 428 repressed genes, 1% false discovery rate, and 50% fold change) including increased expression of genes associated with pathogen recognition molecules and signaling cascades linked to receptors associated with cell mobility and activation. (physiology.org)
- The rapid immune responses are initiated by conserved microbial structures that activate pattern recognition receptors on cell surfaces and in the circulation (e.g., endotoxin, Toll-like receptors, and lipopolysaccharide-binding protein, respectively) ( 6 , 33 ). (physiology.org)
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis in several cancer cell lines ( 12 , 13 ) via tumor cell surface receptors that bind TRAIL. (aacrjournals.org)
- Two of these receptors, DR4 and DR5 trigger apoptosis when bound by TRAIL. (aacrjournals.org)
- Stimulation with microbial ligands of Toll-like receptors (TLRs) or the prototypic proinflammatory cytokines, TNF-α or IL-1, induces IκB phosphorylation and ubiquitin-dependent proteasomal degradation resulting in nuclear entry of NF-κB dimers to initiate target gene transcription. (pnas.org)
- VV infects epithelial cells expressing receptors for epidermal growth factor ( 15 , 16 , 17 ), and thus infects many tissues in mice, including those of the ovaries, spleen, liver, and lung. (jimmunol.org)
- Corresponding to the hierarchy of events in Fas-mediated apoptosis, these regulatory mechanisms can be specific for Fas or common to death receptors, or they can affect the apoptotic core machinery of the cell. (sciencemag.org)
- Wrist following cellular receptors on factor xa. (imagenenaccion.org)
- 16 The binding of kinins to their respective receptors activates second messengers in target tissues and triggers biological effects such as vasodilation and vasoconstriction. (ahajournals.org)
- Anlotinib (AL3818) is a novel orally administered multikinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) 1 to 3, fibroblast growth factor receptor 1 to 4, platelet-derived growth factor receptors, and stem cell factor receptor (c-kit). (springer.com)
- Over-stimulation of ErbB receptors results in the increased production of cyclin D1, a signaling molecule that activates cyclin dependent kinases (CDKs), resulting in tumor cell proliferation. (redorbit.com)
- We found that the Erk1/2 family of MAPK, often involved in regulation of cell proliferation, can be activated in response to the stimulation of G protein-coupled receptors, including adrenergic receptors (α 1 -, α 2 -, β 1 - and β 3 -Adrenoceptors) and mitogenic lysophosphatidic acid (LPA) in primary cultured brown adipocytes. (diva-portal.org)
- The AR 3 plays a central role in the regulation of proliferation, differentiation, and apoptosis of prostate cancer cells. (aacrjournals.org)
- By investigating the effects of chloramphenicol on the activation of mouse T cells stimulated with anti-CD3 antibody or staphylococcal enterotoxin B, we found that chloramphenicol induces the differentiation of activated T cells into lymphoblastic leukemia-like cells, characterized by large cell size, multiploid nuclei, and expression of CD7, a maker for immature T cells and T-cell lymphocytic leukemia, thus phenotypically indicating differentiation toward leukemogenesis. (aacrjournals.org)
- High expression of cyclin B1, but not p53, c-myc, and CDC25A, was detected in chloramphenicol-treated activated T cells, which may relate to abnormal cell differentiation. (aacrjournals.org)
- Our findings show that abnormal cell differentiation and inhibition of apoptosis may contribute to the development of leukemia associated with clinical applications of chloramphenicol. (aacrjournals.org)
- Members of the Myc proto-oncogene family encode transcription factors that function in multiple aspects of cell behavior, including proliferation, differentiation, transformation and apoptosis. (sdbonline.org)
- Myc:Max complexes activate transcription, promote proliferation, and block terminal differentiation. (sdbonline.org)
- The present invention provides methods for inducing differentiation of an embryonic stem cell into a motor neuron using a motoneuronotrophic factor (MNTF) or its peptide analogues. (google.com)
- Insulin has classic actions such as increased glucose uptake, decreased hepatic glucose production (HGP), and antilipolytic effects in skeletal muscle, liver, and adipose tissue, as well as nonclassical vasodilatory effects, proliferative actions on vascular smooth muscle cells (VSMCs), effects on the brain (perhaps related to learning and memory), β-cell actions, and general effects increasing growth and differentiation and decreasing apoptosis. (diabetesjournals.org)
- Breast cancer is characterized by excessive cell proliferation, dysregulation of cellular differentiation and insufficient apoptosis [ 3 ]. (bioscirep.org)
- The MyD88 gene was originally described as one of several myeloid differentiation primary response genes that are induced in murine M1 myeloblastic leukemia cells upon stimulation with IL-6. (google.com)
- During the development of all multicellular organisms, cell fate decisions determine whether cells undergo proliferation and differentiation, or apoptosis. (pubmedcentralcanada.ca)
- Calpains are involved in a variety of calcium-regulated cellular processes such as signal transduction, cell proliferation and differentiation, apoptosis, membrane fusion and platelet activation. (alliedacademies.org)
- Signals transmitted by the TGF-β receptor complex trigger various responses by the cell, including the growth and division (proliferation) of cells, the maturation of cells to carry out specific functions (differentiation), cell movement (motility), and controlled cell death (apoptosis). (medlineplus.gov)
- Recent studies have underscored the role of B-cell-activating factor (BAFF), a member of the tumor necrosis factor superfamily, in promoting the survival of malignant B cells, including human multiple myeloma. (aacrjournals.org)
- The intracellular 52-kd RoSSA autoantigen in keratinocytes is up-regulated by tumor necrosis factor ╨Ю┬▒ via tumor necrosis factor receptor I. (docme.ru)
- UVB exposure triggers the release of tumor necrosis factor ␣ (TNF␣) from keratinocytes in the epidermis and from mast cells in the dermis. (docme.ru)
- Fas (also called Apo-1 or CD95) is a death domain-containing member of the tumor necrosis factor receptor (TNFR) superfamily. (sciencemag.org)
- Specifically, MEQ can efficiently protect Rat-2 cells from cell death induced by multiple modes including tumor necrosis factor alpha, C2-ceramide, UV irradiation, and serum deprivation. (asm.org)
- Although reperfusion salvages the myocardium, it also initiates a series of events that result in ventricular arrhythmia and accelerate myocardial apoptosis and necrosis. (ahajournals.org)
- Moreover, genipin attenuated increases in serum tumor necrosis factor-α and HMGB1 in LPS-induced endotoxemia. (springer.com)
- Therefore, tumor cells could also set in motion additional molecular mechanisms to prevent the secondary necrosis derived from abortive apoptosis. (aacrjournals.org)
- Two κB elements within the NF-κB2 promoter mediate tumor necrosis factor alpha-inducible transactivation. (asm.org)
- At its N-terminus, it has a "death domain" (DD) similar to the cytoplasmic signaling domains found in many members of the tumor necrosis factor (TNF) receptor superfamily. (google.com)
- Oxidative stress occurs when the production of reactive oxygen species (ROS) is greater than their catabolism. (wikipedia.org)
- Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor blocade. (allindianpatents.com)
- Low-dose ionizing radiation is regarded as one of factors that finally affect life-span via modification of cell functioning through the mechanisms of oxidative stress, DNA damage, cellular senescence, apoptosis and compensatory proliferation . (exp-oncology.com.ua)
- Adhesion of MM1S and MCCAR multiple myeloma cell lines to KM104 BMSC line transfected with a luciferase reporter vector carrying the BAFF gene promoter (BAFF-LUC) significantly enhanced luciferase activity, suggesting that nuclear factor-κB (NF-κB) activation induced by multiple myeloma adhesion to BMSCs mediates BAFF up-regulation. (aacrjournals.org)
- Moreover, NF-κB is required for Ras-mediated focus-forming activity ( 7 ), and activation of this transcription factor provides protection against apoptosis ( 8 , 9 ). (sciencemag.org)
- However, the mechanism by which p53 activation is regulated, and its involvement in apoptosis of cardiomyocytes remain unknown. (springer.com)
- Procaspase-8 activation is thought to occur through a dimerization process with other procaspase-8 molecules, known as an induced proximity model. (wikipedia.org)
- Unusually, N1 inhibits both apoptosis and NF-κB activation. (biomedsearch.com)
- Thus, the major process of thymic atrophy in this study first involved activation of transcriptional factors FOS/JUN upon LPS binding to TLR4 that caused release of inflammatory factors, thereby inducing inflammatory responses and DNA damage and ultimately cell cycle arrest and thymic injury. (biomedcentral.com)
- Surprisingly, caspase-3 processing and activity have been observed in the absence of apoptosis after polyclonal activation of PBMCs, and in the absence of DNA fragmentation ( 17 )( 18 ). (rupress.org)
- However, there is no evidence yet for a role of caspases during T cell activation, and a recent report suggested that the observed caspase processing was due to the production of granzyme B by CD8 + activated cells and artifactual release during cell lysis of PBMCs ( 19 ). (rupress.org)
- CD40L-expressing stroma protected CLL cells from spontaneous apoptosis and induced resistance to multiple drugs, accompanied by NF-κB activation and Bim repression. (aacrjournals.org)
- It is therefore particularly remarkable that TAK1 deficiency removes the requirements for both an exogenous priming signal, occurring through RIP1-mediated unregulated TNFα secretion, and the second activating signal through deregulation of TNFR1 signaling, enabling NLRP3 activation (see figure). (rupress.org)
- Caspase-3 activation occurs in various lymphocyte subsets. (nih.gov)
- Processing of caspase-3 was similar in both CD4 and CD8 T cell subsets and occurred not only in CD45RO+, but also in the remaining CD45RA+/CD25+ cells (Fig. 3a and Fig. b), further confirming that caspase activation was an early event after TCR triggering. (nih.gov)
- To define gene expression profiles that occur during the initial activation of human innate immunity, we administered intravenous endotoxin ( n = 8) or saline ( n = 4) to healthy subjects and hybridized RNA from blood mononuclear cells (0, 0.5, 6, 24, 168 h) or whole blood (0, 3, 6, 24, 168 h) to oligonucleotide probe arrays. (physiology.org)
- Stem cell factor-induced activation of the GNNK − form was faster and more pronounced than that of the GNNK + form, whose activation, however, lasted for longer. (haematologica.org)
- 7 , 8 Physiological activation of c-Kit occurs upon binding to the ligand stem cell factor (SCF). (haematologica.org)
- In animals, T cells often die rapidly after activation, unless activation occurs in the presence of inflammatory factors. (jimmunol.org)
- Normal T cells activated by superantigen in uninfected mice died as a result of their activation, whereas T cells that were activated during vaccinia infection survived longer in vivo and in culture. (jimmunol.org)
- Acute exposure of responsive T cells to a superantigen results in activation, expansion, and then deletion of these activated cells by apoptosis. (jimmunol.org)
- This Ca2+ can migrate and enters the mitochondria through the Ca2+ uniporter which results in the activation of mitochondrial biological processes or release of different mitochondrial factors. (wikipathways.org)
- The ERK-phosphorylated transcription factor E-twenty six-like (p-ELK1) is increased in its association with the cFOS promoter after activation of the AAR. (chemweb.com)
- In murine macrophage cells, genipin blocked nitric oxide production on stimulation by lipopolysaccharide (LPS)/IFN and inhibited LPS-induced degradation of the inhibitor of nuclear factor (NF)-κB-α (iκB-α) and NF-κB activation. (springer.com)
- Although JNK activation normally occurs in the nucleus, it can also be activated in the mitochondria, usually in association with the increased production of reactive oxygen species (ROS). (aacrjournals.org)
- We previously showed that CXCR4 forms a physical complex with the TCR upon SDF-1 stimulation and that this event is required for prolonged ERK activation in response to SDF-1 and, consequently, for SDF-1 to increase gene transcription and cytokine production in T lymphocytes ( 4 , 5 ). (jimmunol.org)
- The present invention relates to the field of infection and inflammation and, more specifically, to the field of pathogen-induced nuclear factor kappa B activation. (google.com)
- Once in the cytosol, cytochrome c complexes with apoptosis-protease activating factor-1, which, in the presence of ATP, leads to activation of the initiator caspase, caspase-9. (diabetesjournals.org)
- Additionally, studies in leukemia have indicated that the histone deacetylase inhibitor LAQ824 increases apoptosis by decreasing the expression levels of the c-FLIPs. (wikipedia.org)
- We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. (rupress.org)
- One of the activated genes is an inhibitor of cyclin-dependent kinases. (genecards.org)
- Boc-Asp-fmk, a pancaspase inhibitor, inhibited apoptosis, suggesting that the apoptosis sensitivity was regulated upstream of caspase-3. (ahajournals.org)
- We then focused particularly on genes involved in the regulation of the cytoskeleton, one of the processes occurring during carcinogenesis and in the early steps of neoplastic transformation. (biomedcentral.com)
- Factors released by these inflammatory cells lead to transformation of HSCs into a myofibroblast-like phenotype. (nih.gov)
- Indeed, simultaneous induction of proliferation together with a blockage of the apoptosis associated with uncontrolled cell growth is thought to be a crucial step in tumor cell transformation ( 1 ). (aacrjournals.org)
- As factors stimulating proliferation also downregulate p53 expression by enhancing ribosome biogenesis, we hypothesized that IL-6 may cause similar changes in inflamed tissues, thus activating a mechanism that favors neoplastic transformation. (nih.gov)
- Apoptosis decrease in MDS clonal transformation is associated with a substantially longer telomeres. (exp-oncology.com.ua)
- Therefore, interleukin network represents an interesting pharmacological target, modulation of which using either biological or small chemical agents could contribute to suppression of excessive activated immune system and successfully treat the diseases that they are involved in. (intechopen.com)
- Haemophagocytic lymphohistiocytosis (HLH) is a condition in which there is pathological, unregulated cytokine-mediated stimulation of the immune system by functionally defective cyto-toxic Τ lymphocytes (CTLs) and natural killer (NK) cells. (scielo.org.za)
- Apoptosis and related forms of cell death have central importance in development, homeostasis, tumor surveillance, and the function of the immune system. (sciencemag.org)
- Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. (absoluteastronomy.com)
- When insulin stimulates glucose uptake, particularly occurring in muscle, which mediates ∼80% of insulin-stimulated glucose uptake, PI3K stimulates GLUT4 translocation to the cell membrane, leading to facilitated glucose transport into the cell, a site principally affected by insulin resistance. (diabetesjournals.org)
- These results provide an explanation for the requirement of NF-κB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product. (sciencemag.org)
- 17 18 In this study, we examined the potential roles of the tissue kallikrein-kinin system in ischemia/reperfusion injury through the delivery of the human tissue kallikrein gene and show that adenovirus-mediated kallikrein gene delivery significantly attenuated myocardial infarction and apoptosis after ischemia/reperfusion injury in rats. (ahajournals.org)
- Moreover, this repression can be overcome by activated Notch-1, suggesting that NF-κB2 is a novel putative Notch target gene. (asm.org)
- Hepatocyte growth factor (HGF) is a multifunctional gene. (imedpub.com)
- Non-steroidal anti-inflammatory drug (NSAID) activated gene (NAG-1) is a member of the transforming growth factor-beta (TGF-beta) superfamily. (rockland-inc.com)
- The present invention relates to novel siRNA molecules which inhibit the RTP801 gene and to the use of such molecules to treat respiratory disorders of all types (including pulmonary disorders), eye diseases and conditions, microvascular disorders, angiogenesis- and apoptosis-related conditions. (allindianpatents.com)
- Calpain is another crucial factor that has been shown to be involved in LTP induction. (usc.edu)
- This bystander effect of viral infection on activated T cells was independent of effects on the magnitude of the initial T cell response, on induction of Bcl-2 and Bcl-x, on T cell proliferation, and on Fas killing. (jimmunol.org)
- Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. (genecards.org)
- Amino acid (AA) deprivation in mammalian cells activates a collection of signaling cascades known as the AA response (AAR), which is characterized by transcriptional induction of stress-related genes, including FBJ murine osteosarcoma viral oncogene homolog (cFOS). (chemweb.com)
- Seliciclib has been shown to regulate cell cycle checkpoints resulting in the induction of apoptosis. (redorbit.com)
- Apoptosis induction is possible by the telomere region changes at least in individuals with shorter telomeres. (exp-oncology.com.ua)
- Depending on the structure of the prodomain and their function, caspases are typically divided into 3 major groups (Figure 1 A). The caspases with large prodomains are referred to as inflammatory caspases (group I) and initiator of apoptosis caspases (group II), while caspases with a short prodomain of 20-30 amino acids are named effector caspases (group III). (jci.org)
- group III: apoptosis effector caspases. (jci.org)
- The failure of such effects to predict the fate of activated T cells in vivo indicates that virus infections shape T cell responses via mechanisms that differ from those described previously. (jimmunol.org)
- Each step in Fas-mediated apoptosis can be a target of regulatory mechanisms enabling cells to show flexible responses to stimulation by Fas. (sciencemag.org)
- The mechanisms, such as antidysrhythmic drugs, promoting apoptosis. (imagenenaccion.org)
- Programmed cell death (PCD) occurs through a number of different mechanisms, the best understood of which is caspase-dependent apoptosis that can be triggered by extrinsic or intrinsic stimuli. (pubmedcentralcanada.ca)
- Many viruses have evolved mechanisms to avoid or at least to control apoptosis [ 12 ]. (biomedcentral.com)
- There are a number of ways through which cancer cells can bypass normal proliferative mechanisms including producing their own growth-factor ligands, stimulating neighbor cells to produce various growth factors, or by altering cell surfaces to become hyper-responsive to growth factors. (bioline.com)
- It is important to reveal the mechanisms involved in the radiation induced senescence, including the telomere shortening and apoptosis. (exp-oncology.com.ua)
- Therefore, in the current study, the subacute phase of ischemic stroke, characterized by marked apoptosis and inflammation, was divided into three periods according to the start of APZ treatment following MCAO. (spandidos-publications.com)
- Subsequently, active caspases specifically process various substrates that are implicated in apoptosis and inflammation. (jci.org)
- Inflammation is a fundamental physiological process that protects the host against microbial challenges, but can also do great harm if activated inappropriately or excessively. (pnas.org)
- Hence, calcium controls and modulate cell apoptosis and inflammation. (wikipathways.org)
- Taken together, the present results highlight a new mechanism that may link chronic inflammation to cancer, based on p53 downregulation, which is activated by the enhancement of rRNA transcription upon IL-6 exposure. (nih.gov)
- The transcription factor NF-κB is also activated in response to oncogenic Ras ( 6 ), and this regulation occurs largely through the stimulation of the transcriptional function of the NF-κB RelA/p65 subunit ( 7 ). (sciencemag.org)
- The influence of regucalcin on the intra-and extracellular Ca2+ regulation is showed which are both involved in cell proliferation, ion transport and apoptosis and are important in normal kidney function. (wikipathways.org)
- When the regulation of regucalcin and other factors are downregulated and suppressed the kidney fails in functionality and so renal fibrosis will develop. (wikipathways.org)
- SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells. (wikipedia.org)
- LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. (genecards.org)
- To a lesser extent, regulation of Fas expression is also used to control Fas responses, for example, in p53-induced apoptosis. (sciencemag.org)
- As a result, inappropriate regulation of Wnt signaling occurs in several types of cancer, including colon, liver and brain tumors of neuroectodermal origin [ 10 ]. (biomedcentral.com)
- May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed:10426996). (rcsb.org)
- In this article, we present evidence demonstrating that AhR expression and function promote apoptosis in liver cells in response to Fas stimulation. (biomedsearch.com)
- Paradoxically, when tested in animal models, these inhibitors have caused autoinflammatory disorders, though the mechanism through which this occurs was not understood. (rupress.org)
- The objective of this study is to investigate the effect of XAV939 on the proliferation and apoptosis of NB cell lines, and the related mechanism. (biomedcentral.com)