CleavesAntibodyActivatesInhibitorsEnzymeProteaseAssaySubunitRecombinantProteinsEffector caspasesPathwayCleaveCascadeSubstrates includeInitiator caspasesExecutioner caspasePARPNLRP3Cleavage siteAbstractAssaysCytochromeNeurodegenerationFragmentsGenesNucleusPyroptosisNeurodegenerative diseasesCloneInflammatoryInhibitorDomain-containAlzheimer'sStriatalNecrosisToxicitySignificantlyAminoHumanExpression2016MRNAVitroMiceCellHuntingtinProenzymes
Cleaves5
- It reduces the expression of the immunosuppressant cytokine interleukin-10 and cleaves the macrophage suppressing IRAK-M. With respect to neurodegeneration, caspase-6 cleaves HTT in Huntington's and APP in Alzheimer's disease. (wikipedia.org)
- This protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. (thermofisher.com)
- Caspase-3 cleaves the death substrate PARP to a specific 85 kDa form observed during apoptosis and is inhibitable by the CrmA protein. (thomassci.com)
- They are called cysteine proteases , because they use a cysteine residue to cut those proteins, and are called caspases because the cysteine residue cleaves their substrate proteins at specific asparagine residues. (wikidoc.org)
- Caspase-2 cleaves at amino acid 552 and caspase-6 at amino acid 586. (thermofisher.com)
Antibody8
- Description: A polyclonal antibody for detection of Caspase-1 from Human, Mouse, Rat. (bd-ibr.org)
- This Caspase-1 antibody is for WB, IHC-P, ELISA. (bd-ibr.org)
- The following product was used in this experiment: Active/Pro-Caspase 3 Monoclonal Antibody (31A1067) from Thermo Fisher Scientific, catalog # MA1-91637, RRID AB_1954999. (thermofisher.com)
- Western Blot analysis of (A) RAW264.7 and (B) NIH-3T3 cell lysate using Active/Pro-Caspase 3 Monoclonal Antibody (31A1067) (Product # MA1-91637). (thermofisher.com)
- The antibody recognizes an epitope in the large domain subunit of Caspase-3. (thermofisher.com)
- For a caspase-9-specific test, 5 μg of pcWNV-Cp-DJY or pcWNV-CpWT was cotransfected with a dominant negative caspase-9 (DN caspase-9) construct, and cleavage of procaspase-9 protein was determined by Western blot analysis with antihuman caspase-9 antibody (MBL, Nagoya, Japan). (cdc.gov)
- The localization pattern of capsid expression was analyzed by immunofluorescent assay in HeLa, 293-T, RD, or SH-SY5Y cells by using anti-His tag antibody as described ( 6 ). (cdc.gov)
- The antibody recognizes both the proform of human caspase-8 (55/50 kDa doublet) as well as the cleaved form (40/36 kDa doublet) on SDS/PAGE. (bdbiosciences.com)
Activates2
- Active caspase-9, in turn, activates executioner caspases-3 and -7. (jneurosci.org)
- the apoptosome (regulated by cytochrome c and the Bcl-2 family ) which activates caspase-9 . (wikidoc.org)
Inhibitors5
- Active recombinant caspases are useful in screening caspase inhibitors, studying enzyme kinetics and regulation, determining substrate specificity, and as a positive control in caspase activity assays. (enzolifesciences.com)
- Useful in studying enzyme regulation and inhibitors, determining target substrate, screening caspase inhibitors, or as a positive control in caspase assays. (enzolifesciences.com)
- The initiation of this cascade reaction is regulated by caspase inhibitors. (wikidoc.org)
- 2CNL: Crystal structures of caspase-3 in complex with aza-peptide epoxide inhibitors. (rcsb.org)
- A favorable network of hydrogen bonds involving the oxyanion hole, catalytic histidine, and the atoms in the prime site of the inhibitor enhance the binding affinity and specificity of the aza-peptide epoxide inhibitors toward caspase-3. (rcsb.org)
Enzyme7
- Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene.CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. (wikipedia.org)
- Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. (wikipedia.org)
- This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. (wikipedia.org)
- Caspase-1 exists in cells as an inactive 45kDa pro-enzyme. (enzolifesciences.com)
- In THP-1 cells, a large proportion of the caspase-1 is present in the inactive pro-enzyme form. (enzolifesciences.com)
- However, the function of ICAD/DFF45 is to restrain the enzyme CAD (Caspase Activated DNase). (wikidoc.org)
- Horvitz and his colleague Junying Yuan [2] found in 1993 that the protein encoded by the ced-3 gene was a cysteine protease with similar properties to the mammalian interleukin-1-beta converting enzyme (ICE) (now known as caspase 1) which at the time was the only known caspase. (wikidoc.org)
Protease4
- This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
- Here we demonstrate that, during brain maturation, the potential of the intrinsic apoptotic pathway is progressively reduced and that such repression is associated with downregulation of apoptotic protease-activating factor-1 (Apaf-1) and caspase-3 gene expression. (jneurosci.org)
- MCF-7) and this phenotype is blocked by overexpression of the caspase-3 protease inhibitor, CrmA. (bdbiosciences.com)
- We show that a cysteine-aspartic protease of the apoptosis cascade, caspase-6, serves as an important host factor for efficient coronavirus replication. (cdc.gov)
Assay5
- 6-OAP induces apoptosis in multiple myeloma (MM) cells, as detected by DNA fragmentation assay. (spandidos-publications.com)
- We recommend using 1U per assay for analyzing caspase activity. (enzolifesciences.com)
- To evaluate the induction of apoptosis was carried-out by caspase-9 colorimetric assay and double staining acridine orange-ethidium bromide. (ijsr.net)
- The results of the study revealed the cell chemotactic migration activity were markedly suppressed by docetaxel hydrate followed by the induction of apoptosis through caspase-9 activity and double staining assay. (ijsr.net)
- Exposure of human hepatocytes to doses of fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfinyl]-1H-pyrazole-3-carbonitrile) ranging from 0.1 to 25 µM resulted in a dose dependent increase in CYP1A1 mRNA expression (3.5 to approximately 55-fold) as measured by the branched DNA assay. (cdc.gov)
Subunit4
- Whereas only partial caspase-3A encoding sequences were isolated, the full-length caspase-3B cDNA encodes the inactive proenzyme of 279 amino acids (aa) consisting of an N-terminal prodomain and the large and the small subunit. (nofima.no)
- The deduced salmon caspase-7 consists of only 245 aa and lacks the prodomain and part of the large subunit similar to the predicted caspase-7 of the puffer fish Tetraodon sp. (nofima.no)
- As such it will recognize pro Caspase-3 and the large subunit cleavage fragment. (thermofisher.com)
- They are first synthesized as inactive pro-caspases , that consist of a prodomain, a small subunit and a large subunit. (wikidoc.org)
Recombinant1
- Full-length recombinant human caspase-3 protein was used as immunogen. (thermofisher.com)
Proteins3
- initiator caspases (caspases 2, 8, 9 and 10), which are able to hydrolyse and activate a second family of effector caspases (caspases 3, 6 and 7), which themselves are able to hydrolyse further cellular proteins to bring about programmed cell death. (guidetopharmacology.org)
- Caspases are essential in cells for apoptosis , one of the main types of programmed cell death in development and most other stages of adult life, and have been termed "executioner" proteins for their roles in the cell. (wikidoc.org)
- Viral proteins (v-FLIPS) which inhibit recruitment and activation of caspase-8 have been isolated. (bdbiosciences.com)
Effector caspases3
- CASP2 , CASP8 , CASP9 and CASP10 ) cleave inactive pro-forms of effector caspases, thereby activating them. (wikidoc.org)
- Initiator caspases possess a longer prodomain than the effector caspases, whose prodomain is very small. (wikidoc.org)
- This allows them to autoactivate, so that they can then proceed to activate the effector caspases. (wikidoc.org)
Pathway9
- However, whether 6-OAP-induced mitosis arrest and pathway inhibition are followed by apoptosis requires further study. (spandidos-publications.com)
- These results suggest that differential expression of Apaf-1 and caspase-3 genes may underlie regulation of apoptotic susceptibility during brain development, as well as after acute injury to mature brain, through the intrinsic pathway of caspase activation. (jneurosci.org)
- Eldadah and Faden, 2000 ), we hypothesized that suppression of apoptotic capability during maturation of mammalian brain results from repression of genes involved in the caspase-3 activation pathway, and that injury-induced neuronal apoptosis in the mature brain results from reactivation of these genes. (jneurosci.org)
- Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. (cdc.gov)
- Though inducing more significantly pyroptosis by activating Caspase-1/GSDMD pathway, OP-B relieved DDP resistance of A549 cells. (researchsquare.com)
- The activation of classical and non-classical pathway is separately dependent on Caspase-1 or Caspase-4/5/11 (6, 7). (researchsquare.com)
- combined BI2536 (an inhibitor of PLK1) with cisplatin (DDP) to treat ESCC cells and found the combination of two drugs had a synergistic effect on tumor inhibition and resulted in pyroptotic death of cancer cells by Caspase-3/GSDME pathway. (researchsquare.com)
- Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. (cdc.gov)
- We observed that the WNV-Cp protein is a pathogenic protein, which drives apoptosis in vitro through the mitochodrial/caspase-9 pathway. (cdc.gov)
Cleave3
- This study discovered that the inflammatory toxicity promotes caspase-6 to cleave p62 at a novel site D256. (plymouth.ac.uk)
- Routinely tested for its ability to cleave the caspase-1 colorimetric substrate Ac-YVAD- p NA (Prod. (enzolifesciences.com)
- Activated Caspase-1/4/5/11 catalyze GSDMD to cleave into GSDMD-N and GSDMD-C fragments, and GSDMD-N can bind and form pores at cell membrane, so as to lead pyroptosis and release IL-1β and IL-18 to extracellular environment (8, 9). (researchsquare.com)
Cascade2
- Involved in the activation cascade of caspases responsible for apoptosis execution. (biossusa.com)
- DN caspase-9 (provided courtesy of Emad S. Alnmeri, Thomas Jefferson University, Philadelphia, PA) has been reported to inhibit the caspase cascade ( 5 ). (cdc.gov)
Substrates include1
- Green fluorogenic peptide substrates include caspase substrates, collagen, calpain substrate, etc., twenty seven all together in the portfolio. (eurogentec.com)
Initiator caspases3
- Initiator caspases (e.g. (wikidoc.org)
- The prodomain of the initiator caspases contain domains such as a CARD domain (e.g. caspases-2 and -9) or a death effector domain (DED) (caspases-8 and -10) that enables the caspases to interact with other molecules that regulate their activation. (wikidoc.org)
- These molecules respond to stimuli which cause the clustering of the initiator caspases. (wikidoc.org)
Executioner caspase1
PARP2
- Enhanced apoptosis was identified following a 48‑h incubation with 6‑OAP (0‑10 µM) that induced a dose‑dependent decrease in pro‑casp‑3 and the cleavage of its substrate, anti‑poly (ADP-ribose) polymerase (PARP). (spandidos-publications.com)
- The mechanism of 6‑OAP cytotoxicity in all cell lines was associated with the induction of apoptosis with the presence of cleaved caspase‑3 and PARP. (spandidos-publications.com)
NLRP31
- To investigate the effect of Goal-Oriented Temperature Therapy on pyroptosis (Pyroptosis measured as a composite of NLRP3, caspase-1, and IL-1Beta protein levels on a venous blood sample using ELISA) in patients with spontaneous circulation after cardiac arrests caused by acute myocardial infarction. (who.int)
Cleavage site1
- These results are consistent with proteolysis of htt at the caspase-6 cleavage site being an important event in mediating neuronal dysfunction and neurodegeneration and highlight the significant role of htt proteolysis and excitotoxicity in HD. (qxmd.com)
Abstract1
- abstract = "2,6-Diisopropylphenol is an intravenous anesthetic agent used for induction and maintenance of anesthesia. (tmu.edu.tw)
Assays1
- The caspase-3 and caspase-9 expressions and DAPI (4′, 6-diamidino-2-phenylindole) staining assays were used to evaluate the apoptotic activity. (mendeley.com)
Cytochrome2
- Injury-induced cytochrome c -specific cleavage of caspase-9 followed by activation of caspase-3 in mature brain correlated with marked increases in Apaf-1 and caspase-3 mRNA and protein expression. (jneurosci.org)
- C5a blockade in the sepsis model almost completely inhibited caspase-3, -6, and -9 activation, significantly preserved cytochrome c in the mitochondrial fraction, and restored Bcl-XL expression. (jci.org)
Neurodegeneration3
- Caspase-6 has known functions in apoptosis, early immune response and neurodegeneration in Huntington's and Alzheimer's disease. (wikipedia.org)
- To determine whether caspase cleavage of htt is a key event in the neuronal dysfunction and selective neurodegeneration in HD, we generated YAC mice expressing caspase-3- and caspase-6-resistant mutant htt. (qxmd.com)
- Mice expressing mutant htt, resistant to cleavage by caspase-6 but not caspase-3, maintain normal neuronal function and do not develop striatal neurodegeneration. (qxmd.com)
Fragments1
- Cleavage of huntingtin (htt) has been characterized in vitro, and accumulation of caspase cleavage fragments represents an early pathological change in brains of Huntington's disease (HD) patients. (qxmd.com)
Genes2
- To examine the involvement of executioner caspases in hyperthermia-induced cell-death in a poikilotherm vertebrate species, five genes encoding caspase-3,-6, and -7 were cloned from Atlantic salmon, and the expression was studied in thermal stressed salmon embryos. (nofima.no)
- The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. (mendeley.com)
Nucleus2
- Activated caspase-6 translocates to the nucleus (Warby et al. (reactome.org)
- The cleavage and inactivation of ICAD/DFF45 by a caspase allows CAD to enter the nucleus and fragment the DNA, causing the characteristic 'DNA ladder' seen in apoptotic cells. (wikidoc.org)
Pyroptosis3
- Cell morphological feature, mitochondrial membrane potential, LDH release rate, production of IL-1β and expression of Caspase-1/GSDMD all showed that pyroptosis happened more significantly in A549/DDP cells than that in A549 cells after OP-B treatment. (researchsquare.com)
- The pyroptosis-related phenotype, including ASC, was identified by immunofluorescence, while levels of NLRP-3, pro-IL-1, and pro-caspase-1 were detected by western blotting. (hindawi.com)
- Pyroptosis is a newly discovered form of cell death that differs from apoptosis and necrosis [ 6 ]. (hindawi.com)
Neurodegenerative diseases1
- Caspase-6 activity is associated with neurodegenerative diseases such as Alzheimer's and Huntington's diseases. (plymouth.ac.uk)
Clone1
- Lysates from control (lanes 1-3) and camptothecin treated Jurkat cells (lanes 4-6) were probed with anti-human caspase-8 (clone 4-1-20, Cat. (bdbiosciences.com)
Inflammatory1
- This is because they are inflammatory caspases, which in concert with CASP1 , are involved in cytokine maturation. (wikidoc.org)
Inhibitor1
- The five crystal structures of caspase-3-aza-peptide epoxide inhibitor complexes reported here reveal the structural basis for the mechanism of inhibition and the specificities at the S1' and the S4 subsites. (rcsb.org)
Domain-contain1
- Caspase recruitment domain-containing protein (Card)9 is a nonredundant adapter protein that functions in the innate immune system in the assembly of multifunctional signaling complexes. (nih.gov)
Alzheimer's2
- It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. (thermofisher.com)
- this coupled with the unwanted apoptosis that occurs with ischaemia or Alzheimer's disease , has boomed the interest in caspases as potential therapeutic targets since they were discovered in the mid 1990s. (wikidoc.org)
Striatal1
- [ 8 ] Caspase inhibition in clonal striatal cells showed no correlation between the reduction of aggregates in the cells and increased survival. (medscape.com)
Necrosis1
- Caspases are a family of calcium -dependent cysteine proteases , which play essential roles in apoptosis (programmed cell death), necrosis and inflammation . (wikidoc.org)
Toxicity1
- Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation. (cdc.gov)
Significantly4
- 2,6-Diisopropylphenol significantly reduced HP-induced oxidative stress. (tmu.edu.tw)
- 2,6-Diisopropylphenol significantly blocked SNP- and HP-induced osteoblast apoptosis. (tmu.edu.tw)
- However, 2,6-diisopropylphenol significantly decreased SNP- and HP-enhanced caspase-3 activities. (tmu.edu.tw)
- Results: Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. (cdc.gov)
Amino1
- The N-terminal region of caspase-8 contains an amino acid sequence, termed the death domain, that facilitates caspase-8-FADD direct interaction. (bdbiosciences.com)
Human6
- The results of our preliminary study demonstrated that 6-OAP inhibits the proliferation of human MM cells by inducing the arrest of mitosis and inhibiting specific key pathways ( 5 ). (spandidos-publications.com)
- Therefore, the aim of the present study was to investigate the apoptotic effect of 6-OAP against human myeloma cells. (spandidos-publications.com)
- Figure 1 : Flow cytometry analysis (surface staining) of human peripheral blood with anti-human CD151 (50-6) PE. (abeomics.com)
- Human HTT caspase cleavage sites generate fragment-specific forms of the protein. (thermofisher.com)
- The possibility that cytotoxic effects were due to apoptosis was indicated by significant time- and dose-dependent induction of caspase-3/7 activity in both HepG2 cells and human hepatocytes. (cdc.gov)
- Consequently, PP2A can increase the activity of caspase 3 by dual mechanisms and thereby promote the apoptotic response in human neutrophils. (lu.se)
Expression4
- The 2-2.5 fold increase in the mRNA expression of the heat shock protein Hsp70 gene coincided with the peak mRNA values of the executioner caspases. (nofima.no)
- Interestingly, cardiac expression of caspase-6AIB was only identified in beat stressed embryos. (nofima.no)
- Altogether, these results shed light on evolutionary aspects of the executioner caspases in vertebrates and their expression in salmon embryos exposed to hyperthermia. (nofima.no)
- In particular, the heat sensitive caspase-6 expression in the embryonic heart is of interest since cardiac malformations are an emergent problem in salmon aquaculture. (nofima.no)
20162
- 2016 , 53 (6), 4094-4125. (benthamscience.com)
- 2016 , 11 (6), 865-874. (benthamscience.com)
MRNA2
- Increased apoptotic activity as evidenced by cleavage of nuclear DNA was demonstrated in salmon embryos incubated at 18-20 degrees C for 84h after acclimatization at 8 degrees C. Hyperthermia-induced activation of the executioner caspases was indicated by the increased mRNA levels of caspase-3B, caspase-6A/B and caspase-7 after 54 h heat exposure as quantified by real-time RT-PCR. (nofima.no)
- Whole-mount in situ hybridization of the salmon embryo identified caspase-7 mRNA in the lens exclusively, while caspase-3B and caspase-6A/B were expressed in multiple tissues of exposed and control embryos. (nofima.no)
Vitro1
- In vitro studies showed successful exon skipping and appearance of a shorter huntingtin protein, that is resistant to caspase 6 cleavage. (bmj.com)
Mice8
- Moreover, caspase-6-generated p62N was found in brain tissue lysates of aged and Huntington's disease mice. (plymouth.ac.uk)
- Furthermore, caspase-6-resistant mutant htt mice are protected against neurotoxicity induced by multiple stressors including NMDA, quinolinic acid (QA), and staurosporine. (qxmd.com)
- Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. (cdc.gov)
- Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. (cdc.gov)
- Light microscopy revealed greater liver vacuolation in C57BL/6 mice and a nanoceria-induced decrease in BALB/c but not C57BL/6 mice vacuolation. (cdc.gov)
- Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. (cdc.gov)
- Ferritin accumulation was greatly increased proximal to the nanoceria, forming core-shell-like structures in C57BL/6 but even distribution in BALB/c mice. (cdc.gov)
- Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. (cdc.gov)
Cell8
- Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (wikipedia.org)
- 2,6-Diisopropylphenol protected osteoblasts from SNP- and HP-induced cell damage. (tmu.edu.tw)
- This study shows that a therapeutic concentration of 2,6-diisopropylphenol can protect osteoblasts from SNP- and HP-induced cell insults, possibly via suppression of caspase-3 activities. (tmu.edu.tw)
- The importance of caspases to apoptosis and programmed cell death was originally established by Robert Horvitz and colleagues who found that the ced-3 gene was required for the cell death that took place during the development of the nematode C. elegans . (wikidoc.org)
- All the compounds exhibited antiproliferative activity against the HCT-116 cell line with IC50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15, 32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 μg/mL for compounds 1 to 6, respectively. (mendeley.com)
- All the compounds produced a significant reduction in HCT-116 cell line proliferation, except compounds 2 and 6. (mendeley.com)
- Overexpression of caspase-8 is sufficient to induce apoptosis in certain cell lines (e.g. (bdbiosciences.com)
- Fipronil mediated activation of caspase-3/7 in concurrence with compromised ATP production and viability are attributed to apoptotic cell death. (cdc.gov)
Huntingtin1
- Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. (qxmd.com)
Proenzymes1
- The salmon caspase-6A and caspase-6B proenzymes include an additional linker region between the two subunits. (nofima.no)