Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We isolated mouse CPP32/apopain cDNA, a mammalian homologue most closely related to Ced-3 in C. elegans, and examined the involvement of CPP32 in the apoptosis of nervous system during development. CPP32 is specifically expressed in the trigeminal (V) ganglia, facio-acoustic (VII-VIII) ganglion complex, and dorsal root ganglia (DRGs) of mouse 10.5-day embryos. CPP32-like proteases are activated during apoptosis of DRG neurons induced by deprivation of NGF and serum. Ac-DEVD-CHO, an inhibitor for CPP32-like proteases, prevents apoptosis of DRG neurons, but Ac-YVAD-CHO, an inhibitor for ICE-like proteases, does not. These results suggest that CPP32 or CPP32-like proteases play a role as central mediator in the apoptosis of DRG neurons induced by lack of neurotrophin signals.
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PMID:Specific expression of CPP32 in sensory neurons of mouse embryos and activation of CPP32 in the apoptosis induced by a withdrawal of NGF. 907 Aug 90

The caspase family proteases are principal components of the apoptotic pathway. In this study we demonstrate that caspase-1-like proteases and interleukin-1 beta are important for death induced by various stimuli in cell lines, primary fibroblasts and primary sensory neurons. Furthermore, we show by immunohistochemistry that during the cell death process endogenous caspase-1-like proteases translocate into the nucleus. This translocation is stimulated by interleukin-1 receptor activation. Translocation of caspase-1-like proteases and cell death can be partially prevented by blocking the interleukin-1 receptor with the interleukin-1 receptor antagonist. This finding offers for the first time a mechanistic explanation for the protective effect of the interleukin-1 receptor antagonist against cell death. Furthermore, our data suggest that caspase-1-like proteases have a function in the nucleus which is necessary for completion of the cell death program. In cultured DRG neurons from embryonic mice the combined inhibition of caspases and the interleukin-1 receptor have an additive effect and fully prevent semaphorin III-induced neuronal death. This shows that endogenous caspases work together with IL-1 beta in Semaphorin III-induced neuronal death. We hypothesize that the cell death process involves a double activation step, probably including an interleukin-1 autocrine loop. This model can explain our finding that combined inhibition of caspases and interleukin-1 receptor is necessary to strongly inhibit the cell death process.
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PMID:Prevention of nuclear localization of activated caspases correlates with inhibition of apoptosis. 1123 40

The interleukin-1beta converting enzyme (ICE) gene family, (homologues of C. elegans cell death gene product Ced-3) plays an important role in controlling programmed cell death. Nerve growth factor (NGF) promotes survival of cultured embryonic chicken dorsal root ganglion neurons. Ciliary ganglion neurons depend exclusively on ciliary neurotrophic factor (CNTF) for survival. Complete depletion of NGF or CNTF from culture medium induces apoptosis in both types of neurons. We can prevent apoptosis, due either to NGF or CNTF withdrawal and in either type of neuron, by overexpression of a mutant inactive ICE and an ICE inhibitor, the product of cowpox virus gene crmA. Bcl-2 does not prevent apoptosis in CNTF-dependent ciliary neurons or DRG neurons as it does in NGF-dependent neurons. These results suggest that neuronal cell death is mediated through a common effector mechanism involving the Ice family of genes, whereas different suppression mechanisms are engaged depending upon the specific neurotrophic factors present.
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PMID:Prevention of apoptosis in CNTF-dependent neurons by a mutant ICE and by viral protein CrmA but not by proto-oncogene product Bcl-2. 1718 61