Disease relevance of Casp8

• Caspase 8-mediated cleavage of plectin precedes F-actin breakdown in acinar cells during pancreatitis [1].
• Moreover, AEA caused cell death in caspase-3-deficient MCF-7 cell line and showed similar cytotoxic effects in caspase-9 dominant-negative, caspase-8 dominant-negative or mock-transfected SH-SY5Y neuroblastoma cells [2].
• Adenoviral expression of FADD-dn inhibited caspase-8 activation as well as hypoxia/SD-induced apoptosis at 24 h in an moi (multiplicity of infection)-dependent manner [3].
• Retinal detachment resulted in the transcriptional upregulation of the FAS-receptor, FAS-ligand, caspase-8 and BID, but not caspase-9 and cytochrome c. CONCLUSIONS: The FAS-mediated apoptosis pathway becomes activated and transcriptionally upregulated after retinal detachment [4].
• Caspase 8 activity increased in the myopathy group [5].

Psychiatry related information on Casp8

• Beta-amyloid of Alzheimer's disease activates an apoptotic pathway via caspase-8 [6].

High impact information on Casp8

• Some of these, such as caspase-8, mediate signal transduction downstream of death receptors located on the plasma membrane [7].
• ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm [8].
• Inhibition of caspase-8 blocked polyglutamine-induced cell death [9].
• We show here that caspase-8 is required for the death of primary rat neurons induced by an expanded polyglutamine repeat (Q79) [9].
• CONCLUSIONS: Induction of apoptosis by hydrophobic bile salts involves EGF-R activation and EGF-R-dependent CD95 tyrosine phosphorylation, which triggers CD95 membrane targeting and Fas-associated death domain/caspase-8 recruitment [10].

Chemical compound and disease context of Casp8

• Purified photoproducts of merocyanine 540 trigger cytochrome C release and caspase 8-dependent apoptosis in human leukemia and melanoma cells [11].

Biological context of Casp8

• Loss of Rb-E2F repression results in caspase-8-mediated apoptosis through inactivation of focal adhesion kinase [12].
• The caspase-8 inhibitor Z-IETD-FMK inhibited cell death associated with differentiation in a dose-dependent manner [13].
• Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of beta-amyloid on rat brain microvascular endothelial cells [14].
• RESULTS: In gastric mucosa, sepsis induced upregulation of bax and downregulation of caspase-8 expression (p = 0.053 and p = 0.05, respectively) [15].
• After 24-h exposure, TNF-alpha increased caspase-8 activities, mitochondrial cytochrome C (Cyt C) release to the cytosol, accompanied by loss of mitochondrial transmembrane potential (delta psi(m)) [16].

Anatomical context of Casp8

• C5b-9 terminal complex protects oligodendrocytes from apoptotic cell death by inhibiting caspase-8 processing and up-regulating FLIP [13].
• This derepression of Rb-E2F-regulated genes leads to apoptosis through inactivation of focal adhesion kinase and activation of caspase-8 [12].
• Contribution of caspase-8 to apoptosis of axotomized rat retinal ganglion cells in vivo [17].
• However, substantial caspase-8 activation could be detected after optic nerve transection as shown by a fluorogenic activity assay and Western blot analysis [17].
• Increase in the expression of the death receptor Fas was revealed by RT-PCR analysis, Western blotting, and immunohistochemistry, as was activation of caspase-8 in cortex and thalamus [18].

Associations of Casp8 with chemical compounds

• Caspase 8 activities induced by ANG II were attenuated by U-0126, SP-600125, and CsA [19].
• TMP was found to reduce the adriamycin-stimulated activities of caspase-3, caspase-8 and caspase-9, inhibit adriamycin-induced release of cytochrome C, and elevate the expression of Bcl-x (L) [20].
• Moreover, caspase-8 activation could again contribute to adenosine-induced cytotoxicity, although the underlying mechanism is currently unknown [21].
• The induction of caspase 3 and 9, but not caspase 8, by NMDA was significantly lower in TRX-treated eyes than in saline-treated eyes [22].
• Cell death was partially blocked by cyclosporine A [an inhibitor of the mitochondrial permeability transition (MPT) process], z-VAD (a pan-caspase inhibitor) and inhibitors of caspase-9 and -3 but not by a caspase-8 inhibitor [23].

Regulatory relationships of Casp8

• These data suggest that C5b-9 through PI3K signaling can rescue OLG from Fas-mediated apoptosis by regulating caspase-8 processing [13].
• Finally, we show that the caspase 8 inhibitor Ac-IETD-CHO was more effective at blocking seizure-induced cell death than the caspase 9 inhibitor Ac-LEHD-CHO [24].
• Although caspase-8 is known to be involved in death-receptor-dependent apoptosis, measurable caspase-8 activity or even RGC death could be induced by neither tumor necrosis factor-alpha nor Fas ligand injections into unlesioned eyes [17].
• Therefore, these results suggest that TNF-alpha-induced increase in apoptosis in ARVM results from caspase-8-dependent impairment of mitochondrial integrity [16].
• This death was shown to be caspase dependent in primary neuronal cultures and was blocked by the selective caspase 8 inhibitor IETD [25].

Other interactions of Casp8

• Under this condition, we found that caspase-8 processing was increased in association with Bid cleavage and markedly reduced expression of cellular FLIP long isoform protein [13].
• In the present study, we examined the possible involvement of the caspase-8 and Fas pathway in OLG apoptosis and the role of C5b-9 in this process [13].
• Supramaximal secretory stimulation of acini with CCK leads to a rapid redistribution and activation of caspase 8, followed by degradation of plectin that in turn precedes the F-actin breakdown [1].
• Moreover, GCDCA-induced apoptosis was increased by ECDP, as revealed by enhanced Bax-alpha/Bcl-2 ratio (both in AHs and FHs) and the activity of caspase-8 (only in AHs) and caspase-3 [26].
• BLM exposure had no marked effect on AM expression of TNF-R1 or caspase-8 activation, but significantly increased the expression of TNF-R2 that was accompanied by a rise in c-IAP1 and a decrease in TRAF2 [27].

Analytical, diagnostic and therapeutic context of Casp8

• Apoptosis was determined by TUNEL staining, active caspase-3 staining, and by activation of caspase-8, caspase-9, and caspase-3 [28].
• On immunoblotting, there was an increase of the proform of both caspase-8 and caspase-9 in Cy/Cy kidneys [29].
• Immunoprecipitation was performed to assess for FAS-receptor/FAS-ligand complex formation, and activation of caspase-8 and BID (a member of the Bcl-2 family of proteins) was assessed by Western blot analysis [4].
• Additionally, caspase-8-mediated BID processing was observed only during reperfusion [30].
• The apoptotic cascade is initiated either by mitochondrial damage and activation of caspase-9 or by death receptor ligation and activation of caspase-8 [30].

References