Caspase 3
Caspase 9
Caspase Inhibitors
Caspase 8
Caspase 7
Caspases
Caspase 1
Caspase 10
Apoptosis
Amino Acid Chloromethyl Ketones
Cysteine Proteinase Inhibitors
Caspase 12
Caspase 14
Enzyme Activation
DNA Fragmentation
Proto-Oncogene Proteins c-bcl-2
Cytochromes c
Mitochondria
Antigens, CD95
Cytochrome c Group
X-Linked Inhibitor of Apoptosis Protein
Poly(ADP-ribose) Polymerases
Apoptotic Protease-Activating Factor 1
bcl-2-Associated X Protein
Cell Death
Inhibitor of Apoptosis Proteins
Jurkat Cells
Caspases, Initiator
In Situ Nick-End Labeling
Cell Survival
BH3 Interacting Domain Death Agonist Protein
Apoptosis Regulatory Proteins
Signal Transduction
Cysteine Endopeptidases
Fas-Associated Death Domain Protein
Enzyme Inhibitors
bcl-X Protein
Apoptosis Inducing Factor
Blotting, Western
Tumor Cells, Cultured
Cells, Cultured
CASP8 and FADD-Like Apoptosis Regulating Protein
Staurosporine
Annexin A5
Membrane Potential, Mitochondrial
Carrier Proteins
HL-60 Cells
TNF-Related Apoptosis-Inducing Ligand
HeLa Cells
Necrosis
Caspases, Effector
Apoptosomes
Reactive Oxygen Species
Tumor Necrosis Factor-alpha
Transfection
Proteins
CRADD Signaling Adaptor Protein
Intracellular Signaling Peptides and Proteins
Death Domain Receptor Signaling Adaptor Proteins
Dose-Response Relationship, Drug
Flow Cytometry
Phosphatidylserines
CARD Signaling Adaptor Proteins
bcl-2 Homologous Antagonist-Killer Protein
Calpain
Granzymes
Proto-Oncogene Proteins
Mitochondrial Proteins
Tumor Suppressor Protein p53
Receptor-Interacting Protein Serine-Threonine Kinases
Antineoplastic Agents, Phytogenic
RNA, Small Interfering
Amino Acid Sequence
Receptors, Tumor Necrosis Factor
Receptors, TNF-Related Apoptosis-Inducing Ligand
Cytosol
bcl-Associated Death Protein
Molecular Sequence Data
NF-kappa B
Serpins
JNK Mitogen-Activated Protein Kinases
Etoposide
U937 Cells
Genes, bcl-2
Adaptor Proteins, Signal Transducing
Mitochondrial Membranes
Models, Biological
Down-Regulation
Ceramides
Immunoblotting
Neurons
Protein Structure, Tertiary
Cell Cycle
Phosphorylation
Reverse Transcriptase Polymerase Chain Reaction
Microscopy, Fluorescence
Mice, Knockout
Receptor-Interacting Protein Serine-Threonine Kinase 2
Protein Synthesis Inhibitors
Myeloid Cell Leukemia Sequence 1 Protein
Mutation
Up-Regulation
Drosophila Proteins
Substrate Specificity
Membrane Potentials
Cell Nucleus
Neoplasm Proteins
Autophagy
RNA Interference
Protein-Serine-Threonine Kinases
Coumarins
RNA, Messenger
Protein Processing, Post-Translational
Oxidative Stress
Intracellular Membranes
Protein Binding
Immunohistochemistry
Mitogen-Activated Protein Kinases
Propidium
Receptors, Death Domain
Proto-Oncogene Proteins c-akt
Cycloheximide
Membrane Proteins
Rats, Sprague-Dawley
Protease Inhibitors
Drug Screening Assays, Antitumor
Receptors, Tumor Necrosis Factor, Type I
p38 Mitogen-Activated Protein Kinases
Proteolysis
Protein Transport
Serine Endopeptidases
Disease Models, Animal
DNA Damage
Acetylcysteine
Proteasome Endopeptidase Complex
Cell-Free System
Ultraviolet Rays
Fibroblasts
Hydrogen Peroxide
Drug Resistance, Neoplasm
Gene Expression Regulation
Gene Expression
Endoplasmic Reticulum Stress
Epithelial Cells
Recombinant Fusion Proteins
Microscopy, Confocal
Cell Division
Neuroprotective Agents
Cell Line, Transformed
Lamins
Drosophila
Sequence Homology, Amino Acid
Gene Expression Regulation, Neoplastic
Microtubule-Associated Proteins
Cytoplasm
Gene Knockdown Techniques
Permeability
DNA Primers
Nuclear Proteins
Interleukin-1beta
Cathepsin B
Cell Differentiation
Bongkrekic Acid
Hepatocytes
Mice, Transgenic
Doxorubicin
Cytoprotection
Aspartic Acid
L-Lactate Dehydrogenase
Protein Kinase C-delta
Gene Expression Regulation, Enzymologic
Lamin Type B
Isatin
Keratin-18
Neuroblastoma
Glutathione
Leupeptins
MAP Kinase Signaling System
Macrophages
Xenograft Model Antitumor Assays
Mitogen-Activated Protein Kinase 8
Endoplasmic Reticulum
Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. (1/149)
Calpains and caspases are two cysteine protease families that play important roles in regulating pathological cell death. Here, we report that m-calpain may be responsible for cleaving procaspase-12, a caspase localized in the ER, to generate active caspase-12. In addition, calpain may be responsible for cleaving the loop region in Bcl-xL and, therefore, turning an antiapoptotic molecule into a proapoptotic molecule. We propose that disturbance to intracellular calcium storage as a result of ischemic injury or amyloid beta peptide cytotoxicity may induce apoptosis through calpain- mediated caspase-12 activation and Bcl-xL inactivation. These data suggest a novel apoptotic pathway involving calcium-mediated calpain activation and cross-talks between calpain and caspase families. (+info)Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. (2/149)
When accumulation of a malfolded protein in the endoplastic reticulum (ER) is induced by various adverse conditions, such as hypoxia, glucose starvation, and perturbation of calcium homeostasis, cells respond to the stress by increasing transcription of genes encoding ER molecular chaperones, a process known as unfolded protein response. The signaling is initiated by IRE1s, ER stress sensors. Alternatively, excessive stress to the ER results in apoptosis. Caspase-12 is known to be essential for this ER stress-induced apoptosis. In this study, we analyzed the detailed regulatory mechanisms of IRE1s during ER stress. We identified c-Jun N-terminal inhibitory kinase (JIK) as a binding partner of IRE1alpha, and JIK was seen to modulate IRE1alpha-TRAF2 (tumor necrosis factor receptor-associated factor 2) complex formation and the resultant alteration to c-Jun N-terminal kinase signaling from IRE1s in response to ER stress. We also demonstrated that TRAF2 interacts with procaspase-12 and promotes the clustering of procaspase-12 and its activation by cleavage in response to ER stress. These results indicate that TRAF2 plays crucial roles not only in the signaling of the c-Jun N-terminal kinase pathway but also in activation of caspase-12 to transduce signals from IRE1s. Thus, we provide a missing link in the ER stress-induced apoptosis-signaling pathway, one which connects the stress sensor molecule IRE1 and the activation of caspase-12. (+info)Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. (3/149)
The endoplasmic reticulum (ER) is the site of assembly of polypeptide chains destined for secretion or routing into various subcellular compartments. It also regulates cellular responses to stress and intracellular Ca(2+) levels. A variety of toxic insults can result in ER stress that ultimately leads to apoptosis. Apoptosis is initiated by the activation of members of the caspase family and serves as a central mechanism in the cell death process. The present study was carried out to determine the role of caspases in triggering ER stress-induced cell death. Treatment of cells with ER stress inducers such as brefeldin-A or thapsigargin induces the expression of caspase-12 protein and also leads to translocation of cytosolic caspase-7 to the ER surface. Caspase-12, like most other members of the caspase family, requires cleavage of the prodomain to activate its proapoptotic form. Caspase-7 associates with caspase-12 and cleaves the prodomain to generate active caspase-12, resulting in increased cell death. We propose that any cellular insult that causes prolonged ER stress may induce apoptosis through caspase-7-mediated caspase-12 activation. The data underscore the involvement of ER and caspases associated with it in the ER stress-induced apoptotic process. (+info)Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation. (4/149)
Endoplasmic reticulum (ER) stress elicits protective responses of chaperone induction and translational suppression and, when unimpeded, leads to caspase-mediated apoptosis. Alzheimer's disease-linked mutations in presenilin-1 (PS-1) reportedly impair ER stress-mediated protective responses and enhance vulnerability to degeneration. We used cleavage site-specific antibodies to characterize the cysteine protease activation responses of primary mouse cortical neurons to ER stress and evaluate the influence of a PS-1 knock-in mutation on these and other stress responses. Two different ER stressors lead to processing of the ER-resident protease procaspase-12, activation of calpain, caspase-3, and caspase-6, and degradation of ER and non-ER protein substrates. Immunocytochemical localization of activated caspase-3 and a cleaved substrate of caspase-6 confirms that caspase activation extends into the cytosol and nucleus. ER stress-induced proteolysis is unchanged in cortical neurons derived from the PS-1 P264L knock-in mouse. Furthermore, the PS-1 genotype does not influence stress-induced increases in chaperones Grp78/BiP and Grp94 or apoptotic neurodegeneration. A similar lack of effect of the PS-1 P264L mutation on the activation of caspases and induction of chaperones is observed in fibroblasts. Finally, the PS-1 knock-in mutation does not alter activation of the protein kinase PKR-like ER kinase (PERK), a trigger for stress-induced translational suppression. These data demonstrate that ER stress in cortical neurons leads to activation of several cysteine proteases within diverse neuronal compartments and indicate that Alzheimer's disease-linked PS-1 mutations do not invariably alter the proteolytic, chaperone induction, translational suppression, and apoptotic responses to ER stress. (+info)Wild-type, mitochondrial and ER-restricted Bcl-2 inhibit DNA damage-induced apoptosis but do not affect death receptor-induced apoptosis. (5/149)
The proto-oncogene Bcl-2 is expressed in membranes of mitochondria and endoplasmic reticulum and mediates resistance against a broad range of apoptotic stimuli. Although several mechanisms of Bcl-2 action have been proposed, its role in different cellular organelles remains elusive. Here, we analyzed the function of Bcl-2 targeted specifically to certain subcellular compartments in Jurkat cells. Bcl-2 expression was restricted to the outer mitochondrial membrane by replacing its membrane anchor with the mitochondrial insertion sequence of ActA (Bcl-2/MT) or the ER-specific sequence of cytochrome b5 (Bcl-2/ER). Additionally, cells expressing wild-type Bcl-2 (Bcl-2/WT) or a transmembrane domain-lacking mutant (Bcl-2/DeltaTM) were employed. Apoptosis induced by ionizing radiation or by the death receptors for CD95L or TRAIL was analyzed by determination of the mitochondrial membrane potential (DeltaPsi(m)) and activation of different caspases. Bcl-2/WT and Bcl-2/MT strongly inhibited radiation-induced apoptosis and caspase activation, whereas Bcl-2/DeltaTM had completely lost its anti-apoptotic effect. Interestingly, Bcl-2/ER conferred protection against radiation-induced mitochondrial damage and apoptosis similarly to Bcl-2/MT. The finding that ER-targeted Bcl-2 interfered with mitochondrial DeltaPsi(m) breakdown and caspase-9 activation indicates the presence of a crosstalk between both organelles in radiation-induced apoptosis. By contrast, Bcl-2 in either subcellular position did not influence CD95- or TRAIL-mediated apoptosis. (+info)Formation of noncanonical high molecular weight caspase-3 and -6 complexes and activation of caspase-12 during serum starvation induced apoptosis in AKR-2B mouse fibroblasts. (6/149)
Apoptosis is mainly brought about by the activation of caspases, a protease family with unique substrate selectivity. In mammals, different complexes like the DISC complex or the apoptosome complexes have been delineated leading to the cleavage and thus activation of the executioner caspases. Although caspase-3 is the main executioner caspase in apoptosis induced by serum starvation in AKR-2B fibroblasts as demonstrated by affinity labeling with YVK(-bio)D.aomk and partial purification of cytosolic extracts by high performance ion exchange chromatography, its activation is apparently caused by a noncanonical pathway: (1) Expression of CrmA, an inhibitor of caspase-8, failed to suppress apoptosis; (2) There was no formation of high molecular weight complexes of Apaf-1 indicative for its activation. Furthermore no cleavage of caspase-9 was observed. But surprisingly, gelfiltration experiments revealed the distribution of caspase-3 and -6 into differently sized high molecular weight complexes during apoptosis. Though the apparent molecular weights of the complexes containing caspase-3 (600 kD for apoptosome and 250 kD for microapoptosome) are in accordance with recently published data, the activity profiles differ strikingly. In AKR-2B cells caspase-3 is mainly recovered as uncomplexed enzyme and in much lower levels in the apoptosomes. Remarkably, the 600 kD and 250 kD complexes containing activated caspase-3 were devoid of Apaf-1 and cytochrome c. In addition a new 450 kD complex containing activated caspase-6 was found that is clearly separated from the caspase-3 containing complexes. Furthermore, we disclose for the first time the activation of caspase-12 in response to serum starvation. Activated caspase-12 is detectable as non-complexed free enzyme in the cytosol. (+info)Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. (7/149)
Accumulation of misfolded proteins and alterations in Ca2+ homeostasis in the endoplasmic reticulum (ER) causes ER stress and leads to cell death. However, the signal-transducing events that connect ER stress to cell death pathways are incompletely understood. To discern the pathway by which ER stress-induced cell death proceeds, we performed studies on Apaf-1(-/-) (null) fibroblasts that are known to be relatively resistant to apoptotic insults that induce the intrinsic apoptotic pathway. While these cells were resistant to cell death initiated by proapoptotic stimuli such as tamoxifen, they were susceptible to apoptosis induced by thapsigargin and brefeldin-A, both of which induce ER stress. This pathway was inhibited by catalytic mutants of caspase-12 and caspase-9 and by a peptide inhibitor of caspase-9 but not by caspase-8 inhibitors. Cleavage of caspases and poly(ADP-ribose) polymerase was observed in cell-free extracts lacking cytochrome c that were isolated from thapsigargin or brefeldin-treated cells. To define the molecular requirements for this Apaf-1 and cytochrome c-independent apoptosis pathway further, we developed a cell-free system of ER stress-induced apoptosis; the addition of microsomes prepared from ER stress-induced cells to a normal cell extract lacking mitochondria or cytochrome c resulted in processing of caspases. Immunodepletion experiments suggested that caspase-12 was one of the microsomal components required to activate downstream caspases. Thus, ER stress-induced programmed cell death defines a novel, mitochondrial and Apaf-1-independent, intrinsic apoptotic pathway. (+info)Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. (8/149)
Alterations in Ca(2+) homeostasis and accumulation of unfolded proteins in the endoplasmic reticulum (ER) lead to an ER stress response. Prolonged ER stress may lead to cell death. Glucose-regulated protein (GRP) 78 (Bip) is an ER lumen protein whose expression is induced during ER stress. GRP78 is involved in polypeptide translocation across the ER membrane, and also acts as an apoptotic regulator by protecting the host cell against ER stress-induced cell death, although the mechanism by which GRP78 exerts its cytoprotective effect is not understood. The present study was carried out to determine whether one of the mechanisms of cell death inhibition by GRP78 involves inhibition of caspase activation. Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. GRP78 inhibits cytochrome c-mediated caspase activation in a cell-free system, and expression of GRP78 blocks both caspase activation and caspase-mediated cell death. GRP78 forms a complex with caspase-7 and -12 and prevents release of caspase-12 from the ER. Addition of (d)ATP dissociates this complex and may facilitate movement of caspase-12 into the cytoplasm to set in motion the cytosolic component of the ER stress-induced apoptotic cascade. These results define a novel protective role for GRP78 in preventing ER stress-induced cell death. (+info)Necrosis is a type of cell death that occurs when cells are exposed to excessive stress, injury, or inflammation, leading to damage to the cell membrane and the release of cellular contents into the surrounding tissue. This can lead to the formation of gangrene, which is the death of body tissue due to lack of blood supply.
There are several types of necrosis, including:
1. Coagulative necrosis: This type of necrosis occurs when there is a lack of blood supply to the tissues, leading to the formation of a firm, white plaque on the surface of the affected area.
2. Liquefactive necrosis: This type of necrosis occurs when there is an infection or inflammation that causes the death of cells and the formation of pus.
3. Caseous necrosis: This type of necrosis occurs when there is a chronic infection, such as tuberculosis, and the affected tissue becomes soft and cheese-like.
4. Fat necrosis: This type of necrosis occurs when there is trauma to fatty tissue, leading to the formation of firm, yellowish nodules.
5. Necrotizing fasciitis: This is a severe and life-threatening form of necrosis that affects the skin and underlying tissues, often as a result of bacterial infection.
The diagnosis of necrosis is typically made through a combination of physical examination, imaging studies such as X-rays or CT scans, and laboratory tests such as biopsy. Treatment depends on the underlying cause of the necrosis and may include antibiotics, surgical debridement, or amputation in severe cases.
1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.
2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.
3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.
4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.
5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.
6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.
7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.
8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.
9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.
10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.
Neuroblastoma is caused by a genetic mutation that affects the development and growth of nerve cells. The cancerous cells are often sensitive to chemotherapy, but they can be difficult to remove surgically because they are deeply embedded in the nervous system.
There are several different types of neuroblastoma, including:
1. Infantile neuroblastoma: This type of neuroblastoma occurs in children under the age of one and is often more aggressive than other types of the cancer.
2. Juvenile neuroblastoma: This type of neuroblastoma occurs in children between the ages of one and five and tends to be less aggressive than infantile neuroblastoma.
3. Adult neuroblastoma: This type of neuroblastoma occurs in adults and is rare.
4. Metastatic neuroblastoma: This type of neuroblastoma has spread to other parts of the body, such as the bones or liver.
Symptoms of neuroblastoma can vary depending on the location and size of the tumor, but they may include:
* Abdominal pain
* Fever
* Loss of appetite
* Weight loss
* Fatigue
* Bone pain
* Swelling in the abdomen or neck
* Constipation
* Increased heart rate
Diagnosis of neuroblastoma typically involves a combination of imaging tests, such as CT scans and MRI scans, and biopsies to confirm the presence of cancerous cells. Treatment for neuroblastoma usually involves a combination of chemotherapy, surgery, and radiation therapy. The prognosis for neuroblastoma varies depending on the type of cancer, the age of the child, and the stage of the disease. In general, the younger the child and the more aggressive the treatment, the better the prognosis.
Caspase 12
Caspase
Caspase-8 deficiency
Human evolutionary genetics
Caspase-9
Caspase 6
Caspase 10
Caspase-2
Caspase 7
Caspase 14
Caspase 1
Caspase 3
Caspase 8
Caspase-activated DNase
Centroblast
Death regulator Nedd2-like caspase
Pseudogene
Man flu
FL3 (flavagline)
Mylabris phalerata
Chimpanzee genome project
Unfolded protein response
ERN1
Galactomyces
TAOK3
Thirumala-Devi Kanneganti
RFFL
Apoptosis
Envelope glycoprotein GP120
Hsp90 inhibitor
Proto-oncogene tyrosine-protein kinase Src
NOL3
GNLY
PSMD7
HSPA1B
SFRS2IP
Galectin-9
Histone H2B
SPTAN1
TRADD
Pattern recognition receptor
BCL2L13
ENDOG
HSPA8
Find-me signals
WNK3
Luciferase
Nancy Rothwell
Chromosome 16
DNA fragmentation
Lipid signaling
Goniothalamus macrophyllus
NLRP12
PPP3CA
PARP4
Anticancer gene
PTK2
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Apoptosis19
- 1. Conservation of caspase substrates across metazoans suggests hierarchical importance of signaling pathways over specific targets and cleavage site motifs in apoptosis. (nih.gov)
- 7. Hwang-Heuk-San induces apoptosis in HCT116 human colorectal cancer cells through the ROS-mediated activation of caspases and the inactivation of the PI3K/Akt signaling pathway. (nih.gov)
- 13. Involvement of NLRP3/Caspase-1/GSDMD-Dependent pyroptosis in BPA-Induced apoptosis of human neuroblastoma cells. (nih.gov)
- It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES . (nih.gov)
- Caspases play important roles in apoptosis and inflammation. (immunochemistry.com)
- ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
- Peng, Z;Gillissen, B;Richter, A;Sinnberg, T;Schlaak, MS;Eberle, J. Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins . (immunochemistry.com)
- Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). (ebi.ac.uk)
- The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis. (ebi.ac.uk)
- Detects human Caspase-8 precursor in Western blots and a 42 kDa doublet generated during apoptosis. (rndsystems.com)
- Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in granulosa cells. (ed.ac.uk)
- Apoptosis was quantified using a luminescent caspase-3/7 assay. (ed.ac.uk)
- In this study, we used circulating lymphocytes isolated from human blood and found that rotenone (50-250microM, 12-18h) caused apoptosis (phosphatidylserine externalization, caspase 3/7 activation), reactive oxygen species production (superoxide, H2O2), mitochondrial dysfunction (inactivation of complex I, decrease of mitochondria membrane potential, depletion of ATP) and activation of peroxidase activity of mitochondria. (cdc.gov)
- Smac/DIABLO is required for effector caspase activation during apoptosis in human cells. (mpg.de)
- Requirement of caspase-mediated cleavage of c-Abl during stress-induced apoptosis. (mpg.de)
- IMSEAR at SEARO: Role of caspases in apoptosis and disease. (who.int)
- Khanna N, Singh N. Role of caspases in apoptosis and disease. (who.int)
- Caspases are synthesized as precursor molecules that require processing at specific aspartate residues to produce the active enzyme which in turn leads to the cleavage of various death substrates that lead to morphological changes typical of apoptosis. (who.int)
- Since cytotoxic drugs used in chemotherapy of leukemia's and solid tumors cause apoptosis in target cells, elucidating the consequences of proteolytic activity occupies a central role for understanding of the molecular mechanism of apoptosis which can help us to use the caspase inhibitors as targets of therapy. (who.int)
Apoptotic12
- 2. Novel Apoptotic Mediators Identified by Conservation of Vertebrate Caspase Targets. (nih.gov)
- 3. In Vitro Use of Peptide Based Substrates and Inhibitors of Apoptotic Caspases. (nih.gov)
- 5. Functional interplay between caspase cleavage and phosphorylation sculpts the apoptotic proteome. (nih.gov)
- 14. Cleavage of Armadillo/beta-catenin by the caspase DrICE in Drosophila apoptotic epithelial cells. (nih.gov)
- 20. Overlapping cleavage motif selectivity of caspases: implications for analysis of apoptotic pathways. (nih.gov)
- Caspases are often subcategorized as either pro-apoptotic or pro-inflammatory enzymes. (nih.gov)
- Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS . (nih.gov)
- It is known as the initiating caspase for the apoptotic cascade. (rndsystems.com)
- Oligomeric IRE1 can also induce the production of directly apoptotic Caspase 12. (bellbrooklabs.com)
- Understanding the mechanism that causes B.al/rapaav to be resistant to activation of the caspase pathway might reveal the basis of differences in the sensitivity to apoptotic stimuli of tumor and normal cells, a key issue in the field of cancer therapeutics. (biomedcentral.com)
- When the EGL-1 BH3 family protein is produced, it disrupts the cell-protective interaction between the anti-apoptotic CED-9 Bcl-2-family protein and the CED-4 Apaf-1-like protein, releasing CED-4 to activate the pro-apoptotic caspase CED-3 [ 3 - 8 ]. (biomedcentral.com)
- Recent studies using both molecular and cloning approaches, and in vitro systems have identified a class of highly specific proteases, termed caspases, that appear to have an important role in apoptotic execution. (who.int)
Cleavage8
- an expression level of pro-caspase-9 cleavage products (35-37 kD) was compared to 3′-terminal deletion mutant, pcWNV-Cp∆3′ (Cp∆3′) and pcDNA3.1 by Western blot analysis with anti-human caspase-9 mAb. (cdc.gov)
- 13. Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. (nih.gov)
- 17. Caspase cleavage sites in the human proteome: CaspDB, a database of predicted substrates. (nih.gov)
- 18. Caspase-mediated cleavage of APC results in an amino-terminal fragment with an intact armadillo repeat domain. (nih.gov)
- 2. Cleavage of GSDME by caspase-3 determines lobaplatin-induced pyroptosis in colon cancer cells. (nih.gov)
- Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. (ebi.ac.uk)
- We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. (ebi.ac.uk)
- In rabbits treated intracisternally with aggregated Aβ(1- 42), clear evidence of endoplasmic reticulum stress was observed by the activation of caspase-12 and cleavage of caspase-3 in the endoplasmic reticulum. (nih.gov)
Inhibitors4
- A number of these compounds were potent inhibitors of caspase 1 (IC 50 s ≤ 1 nM). (nih.gov)
- It also possesses a unique selectivity pattern relative to other reported caspase inhibitors. (nih.gov)
- Inhibitors of caspase 1 are sought for intervention strategies within ischemic disorders, Huntington's disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, osteoarthritis, inflammatory bowel disease and sepsis. (nih.gov)
- This review discusses caspases, their inhibitors and regulators. (who.int)
Proteins1
- 19. Regulation of caspase pathways by protein kinase CK2: identification of proteins with overlapping CK2 and caspase consensus motifs. (nih.gov)
Pathway6
- 4. Saikosaponin-D induces the pyroptosis of lung cancer by increasing ROS and activating the NF-κB/NLRP3/caspase-1/GSDMD pathway. (nih.gov)
- 9. Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway. (nih.gov)
- 11. Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies. (nih.gov)
- 12. Suppression of the caspase-1/GSDMD-mediated pyroptotic signaling pathway through dexamethasone alleviates corneal alkali injuries. (nih.gov)
- 17. Microglial and Neuronal Cell Pyroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation Aggravates Cell Injury via Activation of the Caspase-1/GSDMD Signaling Pathway. (nih.gov)
- We found that B.al/rapaav is resistant to caspase-pathway activation: the caspase-mediated suicide pathway initiates the cell-death process but is insufficient to cause B.al/rapaav death without the subsequent assistance of engulfment. (biomedcentral.com)
Inhibitor3
- NCGC-00183434) is the most potent caspase 1 inhibitor reported to date. (nih.gov)
- This in vitro assay employs the fluorescent inhibitor probe FAM-LETD-FMK to label active caspase-8 enzyme in living cells. (immunochemistry.com)
- Treatment with lithium, an inhibitor of GSK-3β, inhibited caspase activation but did not prevent mitochondrial DNA damage or tau hyperphosphorylation, suggesting that the translocation of GSK-3β may represent an upstream event that leads to caspase activation but is unrelated to tau hyperphosphorylation or mitochondrial DNA oxidative damage. (nih.gov)
CASP81
- Caspase 8 antibody LS-C301799 is an FITC-conjugated rabbit polyclonal antibody to human Caspase 8 (CASP8) (aa217-384). (lsbio.com)
Endoplasmic reticulum1
- the myogenic differentiation was impaired accompanied by the enhanced caspase 12/3 activation, implying enhanced endoplasmic reticulum (ER) stress. (bvsalud.org)
Assay4
- c , Colorimetric caspase-3 activity assay using pcWNV-Cp-DJY (Cp-DJY), pcWNV-CpWT (CpWT), or pcWNV-CpΔ3′ (CpΔ3') plasmid-transfected cells. (cdc.gov)
- Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. (immunochemistry.com)
- Bulk Order Inquiry for FAM-FLICA® Caspase-8 Assay Kit ------- (please add any order requirements, including desired quantity, timing, etc. (immunochemistry.com)
- The FAM FLICA Caspase-8 assay probe allows researchers to assess caspase-8 activation. (immunochemistry.com)
Proteases2
20232
- Cells;12(14)2023 07 12. (bvsalud.org)
- 12(14)2023 07 12. (bvsalud.org)
Sepsis1
- Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. (anthropogeny.org)
Cells7
- Caspase 1 is constitutively and inducibly expressed in immune response elements such as T cells, macrophages and neutrophils. (nih.gov)
- 1. Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells. (nih.gov)
- 6. Triclabendazole Induces Pyroptosis by Activating Caspase-3 to Cleave GSDME in Breast Cancer Cells. (nih.gov)
- To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. (ebi.ac.uk)
- In mutants deficient in the engulfment process, the vast majority of cells still undergo programmed cell death, but the cell corpses persist unengulfed and only slowly degrade [ 10 - 12 ]. (biomedcentral.com)
- Only a very small number of cells stochastically fail to die in engulfment-defective mutants [ 12 ]. (biomedcentral.com)
- The 12 h micellar uptake by MGC803 and BGC823 cells was sufficient, and the micelles were able to abundantly accumulate at lesion sites in mice thus achieving good passive EPR targeting. (springer.com)
Residues1
- 4. Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues. (nih.gov)
20191
- 2019 Dec;64(12):3630-3641. (nih.gov)
Antibody1
- PVDF membrane was probed with 1 µg/mL of Human Caspase-8 Monoclonal Antibody (Catalog # MAB704), followed by HRP-conjugated Anti-Mouse IgG Secondary Antibody (Catalog # HAF007 ). (rndsystems.com)
Enzyme2
- Caspase 1, also known as interleukin-converting enzyme or ICE, is responsible for the proteolytic activation of interleukin (IL)-1β and IL-18. (nih.gov)
- The remaining green fluorescent signal is a direct measure of the active caspase-8 enzyme activity present in the cell at the time the reagent was added. (immunochemistry.com)
NLRP32
- The receptor NLRP3 is involved in the formation of the NLRP3 inflammasome that activates caspase-1 and mediates the release of interleukin 1β (IL-1β) and IL-18. (nature.com)
- NLRP3, but not the inflammasome adaptor ASC or caspase-1, positively regulated a T H 2 program. (nature.com)
Selectivity1
- Examination of these small molecules versus a caspase panel demonstrated an impressive degree of selectivity for caspase 1 inhibition. (nih.gov)
Phosphorylation1
- 15. Effect of phosphorylation and single nucleotide polymorphisms on caspase substrates processing. (nih.gov)
Protein2
- 11. A peptide-based target screen implicates the protein kinase CK2 in the global regulation of caspase signaling. (nih.gov)
- Procaspase 1 is known to associate with several multi-protein complexes capable of responding to numerous external stimuli, suggesting that caspase 1 is a major regulator of the inflammation response. (nih.gov)
Mice2
- In addition to decreased circadian power and reduced locomotor activity , we found cleaved caspase 1 significantly elevated in the hippocampus of mice exposed to LL. (bvsalud.org)
- MYPT1SMKO mice exhibited remarkable white matter injury compared with control mice, as shown by the more prominent loss of myelin at 12 months of age. (bvsalud.org)
Lysates1
- d , The cell lysates were assayed for caspase-9-like activity, and the pcDNA3.1-transfected cell lysate was used as the negative control. (cdc.gov)
Inflammatory1
- Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. (nature.com)
Cellular1
- 12. Caspase substrates and cellular remodeling. (nih.gov)
Roles2
Human1
- Detection of Human Caspase‑8 by Western Blot. (rndsystems.com)
Active3
- A nitrile-containing propionic acid moiety as an electrophile for covalent attack by the active site cysteine residue of caspase 1 was investigated. (nih.gov)
- Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. (ebi.ac.uk)
- Association with another p18/p10 heterodimer generates active caspase-8. (rndsystems.com)
Months2
- 12 months from date of receipt, -20 to -70 °C as supplied. (rndsystems.com)
- Aliquot and store at -20°C for 12 months. (lsbio.com)
Western1
- This experiment was performed under reducing conditions on the Jess™ Simple Western instrument from ProteinSimple, a BioTechne brand, using the 12-230 kDa separation module. (cellsignal.com)
Cell death1
- 16. Caspases in developmental cell death. (nih.gov)
Domain1
- A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. (nih.gov)
Mouse1
- Acute Circadian Disruption Due to Constant Light Promotes Caspase 1 Activation in the Mouse Hippocampus. (bvsalud.org)
Expression1
- High dose of ligustrazine can significantly enhance the expression of Bcl-2 and reduce the expression of p53 [ 12 ]. (hindawi.com)