Caspase 8. Medical search. Frequent questions

For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase heterotetramer whereas for the activation pathway, the zymogen appears to remain intact perhaps to limit its proteolytic function but enhance its capability as an adapter protein. (wikipedia.org)
Caspase-8 is an initiator enzyme in the Fas-mediated pathway of which the downstream executioner caspase-3 is a physiological target. (rcsb.org)
These results suggest that chemotherapeutic drug-induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function. (diva-portal.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)
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)
Besides its canonical function in initiating the extrinsic pathway of apoptosis, caspase-8 possesses non-apoptotic functions in regulating activation, differentiation and survival of peripheral immune cells. (grantome.com)
These findings highlight the roles of both transcription-dependent and -independent apoptosis by p53 and identify an essential role for caspase-8 in the transcription-independent pathway. (elsevierpure.com)
Surprisingly, although in response to the apoptotic inducer staurosporine PKR itself is not phosphorylated, PKR triggers the cleavage of HuR via its downstream effector FADD that in turn activates the caspase-8/caspase-3 pathway. (edu.sa)
Therefore, our results support a model whereby in response to lethal stress, PKR, without being phosphorylated, activates the FADD/caspase-8/caspase-3 pathway to trigger HuR cleavage, and the HuR-CPs are then capable of promoting apoptosis. (edu.sa)
Von Roretz, C & Gallouzi, IE 2010, ' Protein kinase RNA/FADD/caspase-8 pathway mediates the proapoptotic activity of the RNA-binding protein human antigen R (HuR) ', Journal of Biological Chemistry , vol. 285, no. 22, pp. 16806-16813. (edu.sa)
On how was apoptotic of leidig cell of 18 months male rattus norvegicus testes happened, whether through the pathway of caspase 8 (extrinsic) or through the pathway of caspase 9 (intrinsic). (journalcra.com)
mediated protective immune response following by caspase-1- dependent IL-18 release after is the key mechanism responsible for the fungal control after P. brasiliensis-induced cell damage recognition by NLRP3 canonical inflammasome pathway. (usp.br)
Titanium dioxide nanoparticle s induce JB6 cell apoptosis through activation of the caspase-8/Bid pathway. (cdc.gov)

Caspase-8 is a cytosolic protease that is capable of processing/activating all known caspases, indicating its presence early in the apoptotic cascade. (southernbiotech.com)
Comparison of the absorbance of pNA from an apoptotic sample with an uninduced control allows determination of the fold increase in caspase-8 activity. (sigmaaldrich.com)
In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. (diva-portal.org)
The present study was designed to investigate the role of the miR‑133b‑5p in HPC‑induced cardioprotection and the underlying mechanisms involving caspase‑8 and caspase‑3 apoptotic signaling. (spandidos-publications.com)
Upregulation of miR‑133b‑5p contributes to HPC‑mediated cardioprotection in cardiomyocytes, and the mechanism may be associated with inhibition of caspase‑8 and caspase‑3 apoptotic signaling. (spandidos-publications.com)
Caspase also recognises several structural proteins as substrates, leading to cleavage that is associated with distinct morphological changes in apoptotic cells, including chromatin condensation, nucleus fragmentation, and cytoplasmic integrity. (caltagmedsystems.co.uk)
Although there is no specific marker for necroptosis the combination of H&E TUNEL cleaved caspase-3 staining and ultrastructure is definitely evidence for non-apoptotic necrosis-like cell death (Bonnet et al. (molecularcircuit.com)
We recently showed that in response to severe stress, HuR is cleaved to generate two cleavage products (CPs), HuR-CP1 (24 kDa) and HuR-CP2 (8 kDa), by which it promotes apoptotic cell death. (edu.sa)
caspase 8, caspase 9, Mn SOD and apoptotic was examined using immuno histochemistry. (journalcra.com)
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)
caspases (e.g. caspase-3, -6, and -7) in a cascade-like manner, which cleave key cellular proteins that lead to the morphological changes associated with apoptotic cell death. (enzolifesciences.com)
ABSTRACT This study examined haematopoietic stem cells of 19 high-risk cases of myelodysplastic syndrome (MDS) for apoptotic and anti-apoptotic signals and cellular proliferation and correlated these with clinical and cytogenetic subtypes, particularly trisomy 8. (who.int)
High-risk MDS cases had a significantly higher percentage of apoptotic CD34+ cells and anti-apoptotic survivin+ cells than controls, particularly for trisomy 8 cases. (who.int)
Our results suggest that although trisomy 8 cells are in a pro-apoptotic state, they are checked by the enhanced expression of anti-apoptotic signals which provide them with their proliferative advantage. (who.int)

Caspase-8 is a caspase protein, encoded by the CASP8 gene. (wikipedia.org)
The CASP8 gene encodes a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
Our preliminary data demonstrate that conditional deletion of Casp8 in myeloid cells including microglia results in exacerbated neuroinflammation in animal models of MS, and that caspase-8-deficient microglia exhibit enhanced proinflammatory responses in vitro and in cultured brain slices. (grantome.com)
CASP2 , CASP8 , CASP9 and CASP10 ) cleave inactive pro-forms of effector caspases, thereby activating them. (wikidoc.org)
Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. (uni-koeln.de)
Las causas conocidas incluyen mutaciones en los genes de las proteínas FAS, TNFSF6, ANR, CASP8 y CASP10. (bvsalud.org)

Caspase-8 (FLICE/MACH-1) is a 55 kDa cytosolic protein with homology to the CD95/Fas-associated signal transducer, FADD/MORT-1, as well as to other caspase (ICE/Ced-3) cysteine proteases. (bdbiosciences.com)
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)
FADD therefore acts as an adapter molecule, allowing caspase-8 to become recruited to the cytoplasmic region of Fas following receptor activation. (bdbiosciences.com)
Importantly, caspase-8 activation appears to be independent of FADD, and caspase-8 is found in a novel 600-kDa complex following p53 activation. (elsevierpure.com)
HS-173 2001 Caspase-8- FADD- or FLIP-deficient embryos expire around embryonic time 10.5 connected with failing to upgrade the yolk sac vasculature (Varfolomeev et al. (molecularcircuit.com)
2009 Ablation of RIPK3 fully rescues the development of mice lacking caspase-8 FADD or both FADD and FLIP (Dillon et al. (molecularcircuit.com)
2011 These and additional approaches showed the HS-173 FADD-induced heterodimer of caspase-8 and FLIP suppresses RIPK3-mediated lethality (Dillon et al. (molecularcircuit.com)
this results in cytoplasmic recruitment of a protein known as the FAS-associated death domain (FADD), followed by recruitment of procaspase 8 and procaspase 10 and resultant cellular apoptosis. (medscape.com)

initiator (apical) caspases and effector (executioner) caspases . (wikidoc.org)
Initiator caspases (e.g. (wikidoc.org)
Initiator caspases possess a longer prodomain than the effector caspases, whose prodomain is very small. (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)
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)
Proapoptotic signals autocatalytically activate initiator caspases, such as Caspase-8 and Caspase-9. (neuromics.com)
Activated initiator caspases then process effector caspases, such as Caspase-3 and Caspase-7, which in turn cause cell collapse. (neuromics.com)
Initiator caspases (e.g. caspase-8 and -10) are activated by dimerization of the zymogen on a dedicated adaptor protein. (enzolifesciences.com)
These activated initiator caspases in-turn cleave downstream effector or ?executioner? (enzolifesciences.com)

Caspases are cysteine proteases that are specific for substrates with an aspartic acid residue at the P(1) position and have an optimal recognition motif that incorporates four amino acid residues N-terminal to the cleavage site. (rcsb.org)
The caspases are a family of cysteine proteases that induce apoptosis in response to a variety of intra- and extracellular stimuli. (southernbiotech.com)
Caspases are a family of calcium -dependent cysteine proteases , which play essential roles in apoptosis (programmed cell death), necrosis and inflammation . (wikidoc.org)
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)
Caspases are cysteine proteases, expressed as inactive precursors, that mediate apoptosis by proteolysis of specific substrates. (neuromics.com)
The caspases are a family of cysteine proteases that cleave after certain aspartate residues, and are primarily recognized as mediators of apoptosis. (enzolifesciences.com)

pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. (eurogentec.com)
Active caspase identifies multiple molecules as substrates and cleaves them, leading to biological events associated with apoptosis. (caltagmedsystems.co.uk)
The exact contribution that the cleavage of many caspase substrates makes to the biochemistry and morphology of apoptosis is unclear. (wikidoc.org)

This allows them to autoactivate, so that they can then proceed to activate the effector caspases. (wikidoc.org)

Full-length recombinant human caspase-8 protein was used as immunogen. (bdbiosciences.com)
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)
In addition, binding and immunoprecipitation analyses revealed that the protein - protein interaction between ARC and caspase 8 was decreased by the increase of Ca(2+) concentration in vitro and by the treatment of HEK293 cells with thapsigargin in vivo. (bvsalud.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)
Caspases are heterotetrameric, being made up of two pairs of subunits, generated by a single gene product, which is proteolysed to form the mature protein. (guidetopharmacology.org)
Huntingtin contains a few domains that suggest particular functions, including WW domains and caspase cleavage sites ( 7 , 8 ), but the function of the protein remains unknown. (jci.org)
Full-length recombinant human Caspase 7 protein. (neuromics.com)

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)
Purified Anti-Human Caspase-8 antibody for use in western blot assays. (southernbiotech.com)
The SB125a monoclonal antibody detects a band at ~55kD corresponding to the full length form of caspase-8. (southernbiotech.com)
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)

This disease, called CEDS, stands for "Caspase eight deficiency state. (wikipedia.org)
Unlike caspase-1, caspase-11 deficiency did not impair IL-1? (usp.br)

Caspase 8 Colorimetric Activity Assay Kit, IETD Caspase-8 Colorimetric Activity Assay Kits provide a simple & convenient means for assaying the activity of caspases that recognize the sequence IETD. (sigmaaldrich.com)
MBLI 's APOPCYTO Caspase-3,8,9 Colorimetric Assay Kit detects caspase activity in cell extract with LEHD-pNA as a substrate, in which LEHD sequence is recognised by each active caspase selectively. (caltagmedsystems.co.uk)

Caspase-8 has been classified as a group III caspase member because it shows a preference for a small hydrophobic residue at the P(4) substrate position. (rcsb.org)
The Caspase-8 substrate and pNA standard are especially light sensitive. (sigmaaldrich.com)
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)

Active caspase-9, in turn, activates executioner caspases-3 and -7. (jneurosci.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)

Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex which were crucial for the induction of nuclear translocation of NF-κB. (wikipedia.org)
MCF-7) and this phenotype is blocked by overexpression of the caspase-3 protease inhibitor, CrmA. (bdbiosciences.com)
We report the X-ray crystallographic structure of caspase-8 in complex with benzyloxycarbonyl-Asp-Glu-Val-Asp-aldehyde (Z-DEVD), a specific group II caspase inhibitor. (rcsb.org)
Kinetic data reveal that Z-DEVD (K(i) 2 nM) is an almost equally potent inhibitor of caspase-8 as the specific group III inhibitor Boc-IETD-aldehyde (K(i) 1 nM). (rcsb.org)
For instance, caspase-3 indirectly activates CAD (caspase-activated deoxyribonuclease) while inactivating ICAD (inhibitor of caspase-activated deoxyribonuclease), which contributes to chromatin fragmentation in nucleosome units. (caltagmedsystems.co.uk)

the apoptosome (regulated by cytochrome c and the Bcl-2 family ) which activates caspase-9 . (wikidoc.org)

Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. (wikipedia.org)
Caspase-8 is an apical and critical proteolytic enzyme in the cascade of apoptosis. (elsevierpure.com)
However, the function of ICAD/DFF45 is to restrain the enzyme CAD (Caspase Activated DNase). (wikidoc.org)
secretion is the activation of inflammasomes, large multimolecular complexes best known for their ability to control activation of the proteolytic enzyme caspase-1. (usp.br)
PARP [Poly (ADP-ribose) polymerase] is a 116 kDa nuclear chromatin-associated enzyme that is cleaved during apoptosis by caspase-3 into a 24 kDa fragment containing the DNA binding domain and an 89 kDa fragment containing the catalytic and automodification domains. (novusbio.com)

In contrast, inhibition of ATP production did not affect caspase activation after triggering of CD95. (diva-portal.org)
MiRNAs typically bind to the 3′ untranslated region (UTR) of their mRNA targets and downregulate gene expression via mRNA degradation or translational inhibition ( 8 - 10 ). (spandidos-publications.com)
[ 8 ] Caspase inhibition in clonal striatal cells showed no correlation between the reduction of aggregates in the cells and increased survival. (medscape.com)
We could show that inhibition of COX-2 causes increased apoptosis, mediated through activation of caspase-8, cleavage of Bid and mitochondrial release of cytochrome c. (lu.se)

caspases are synthesized as inactive zymogens that can be cleaved to form active enzymes following the induction of apoptosis by stress or death receptors. (enzolifesciences.com)

Viral proteins (v-FLIPS) which inhibit recruitment and activation of caspase-8 have been isolated. (bdbiosciences.com)

Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (wikipedia.org)
The defect in lymphocyte activation and protective immunity suggested that caspase-8 had additional signaling roles in lymphocytes. (wikipedia.org)
Activation of ICE-family proteases/caspases initiates apoptosis in mammalian cells. (sigmaaldrich.com)
Prevention of ATP production completely inhibited caspase activation and apoptosis in response to chemotherapeutic drugs and staurosporine. (diva-portal.org)
The activation of caspase‑8 and caspase‑3 were measured by western blot analysis to detect the cleaved fragments as well as a colorimetric assay. (spandidos-publications.com)
Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation. (unil.ch)
Based on our recent findings, we propose that caspase-8 is a key modulator for microglial cell activation and CNS inflammation. (grantome.com)
In the CNS, we found that microglia are the predominant cells expressing caspase-8, indicating that caspase-8 may control CNS immunity by regulating microglia activation status and survival. (grantome.com)
We hypothesize that caspase-8 is a gatekeeper that restricts microglia/macrophage activation and that dysregulation of microglial activation may perpetuate pathological CNS inflammatory responses and impair myelin repair. (grantome.com)
In this proposal, we will employ molecular and genetic approaches to determine the mechanism by which caspase-8 regulates microglial activation and inflammatory responses in vitro and in vivo. (grantome.com)
Apoptosis repressor with CARD ( ARC ) possesses the ability not only to block activation of caspase 8 but to modulate caspase -independent mitochondrial events associated with cell death . (bvsalud.org)
Caspase 8 activation was also required for the thapsigargin -induced cell death and suppressed by the ectopic expression of ARC . (bvsalud.org)
Processing of caspases is required for activation of downstream signaling and dsRNA stimulation inducese the processing of these caspases. (reactome.org)
The nonapoptotic caspase function of both caspase-8 and -10 does not require the protease activity and the DED-containing prodomains are sufficient for NF-kB activation. (reactome.org)
Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation. (cdc.gov)

The initiation of this cascade reaction is regulated by caspase inhibitors. (wikidoc.org)

In view of this finding, the original classification of caspases into three specificity groups needs to be modified, at least for caspase-8, which tolerates small hydrophobic residues as well as the acidic residue Asp in subsite S(4). (rcsb.org)
Caspases have the ability to cleave after aspartic acid residues. (neuromics.com)

These substances include apoptosis inducing factor (AIF), apoptosis protease activating factor 1 (apaf 1), cytochrome c and members of the protease family: the caspases. (lu.se)

In a fasting state, increased glucagon and epinephrine and norepinephrine secretion induce autophagy, and glucocorticoids have also been shown to induce autophagy by stimulating the transcription of autophagy genes such as ATG5, LC3, and Beclin-1 in various tissues 8 . (nature.com)
Raro trastorno congénito del tejido linfático debido a mutaciones en ciertos genes de la vía del ligando Fas-Fas. (bvsalud.org)

Caspase belongs to the cysteine aspartic acid-specific protease family, which gets activated by various signals such as death receptor ligation, DNA damage, serum starvation, and stresses. (caltagmedsystems.co.uk)

Calcium binding of ARC mediates regulation of caspase 8 and cell death. (bvsalud.org)
These results suggest that calcium binding mediates regulation of caspase 8 and cell death by ARC . (bvsalud.org)
In this study we addressed the mechanisms that underlie canonical and non-canonical inflammasome pathways, assessing the functional importance of caspase-1, caspase-11 and caspase-8 in the regulation of inflammasome-mediated host resistance during P. brasiliensis infection. (usp.br)

Overexpression of caspase-8 is sufficient to induce apoptosis in certain cell lines (e.g. (bdbiosciences.com)

Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. (wikipedia.org)
They are first synthesized as inactive pro-caspases , that consist of a prodomain, a small subunit and a large subunit. (wikidoc.org)

The clinical phenotype of CEDS patients represented a paradox since caspase-8 was considered to be chiefly a proapoptotic protease, that was mainly involved in signal transduction from Tumor necrosis factor receptor family death receptors such as Fas. (wikipedia.org)

Läkartidningen 50: 5756-5761 (2001)AbstractHuntingtons sjukdom är en av flera kända neurologiska sjukdomar som beror på en expanderad CAG-repetition. (lu.se)

The transcript encoded N-terminal two repeats of death effector domain (DED) of caspase-8, but lacking the C-terminal half of the proteolytic domain. (elsevierpure.com)

RIPK1 also directly regulates caspase-8-mediated apoptosis or, if caspase-8 activity is blocked, RIPK3-MLKL-dependent necroptosis. (nih.gov)

Caspase 3 is the most concentrated on Caspase in mammalian cells. (entigen.com)

Autoimmune lymphoproliferative syndrome due to mutations in CASPASE 8 gene. (bvsalud.org)

Human and some mouse caspases are active in apoptosis and cell death and even in necrosis and inflammation. (biovisi.com)

One is mediated by recruitment of the proximal regulator caspase-8 to the death receptor complex. (diva-portal.org)

Caspase (Cysteine-requiring Aspartate Protease) is a protease family that assumes a significant part during the time spent apoptosis. (entigen.com)

2000 Dec 8;275(49):38905-38911. (elsevierpure.com)

Depletion or inactivation of caspase-8 either in cells or cell-free extracts completely prevents this transcription-independent apoptosis and significantly attenuates overall death induced by wild-type p53. (elsevierpure.com)

2004 No embryonic lethality was noticed when caspase-8 was removed elsewhere like the center (Dillon et al. (molecularcircuit.com)

Here, we report that ARC is a Ca(2+)-dependent regulator of caspase 8 and cell death . (bvsalud.org)

Anatomy24

Organisms5

Diseases3

Chemicals and Drugs119

Analytical, Diagnostic and Therapeutic Techniques and Equipment15

Phenomena and Processes46

Disciplines and Occupations1

Information Science2

Health Care1

Pathway14

Apoptotic14

CASP86

FADD8

Initiator10

Cysteine proteases6

Substrates3

Effector caspases1

Protein7

Antibody5

Deficiency2

Assay Kit2

Substrate3

Active caspase1

Executioner1

Inhibitor5

Activates1

Enzyme5

Inhibition4

Induction of apoptosis1

Proteins1

Activation15

Inhibitors1

Residues2

Cytochrome1

Genes2

Receptor ligation1

Regulation3

Induce1

Subunit2

Proapoptotic1

20011

Proteolytic1

Regulates1

Mammalian cells1

Mutations1

Inflammation1

Proximal1

Protease family1

20001

Inactivation1

Embryonic1

Regulator1