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)

COS cells are resistant to cell death induced either by interleukin-1beta-converting enzyme (*ICE) and ICE homolog (ICH-1L) overexpression or by serum deprivation. COS cells deprived of serum undergo apoptosis after transfection with an ICE expression construct, but not an ICH-1L construct. ICE-mediated apoptosis of COS cells in serum-free medium is suppressed by insulin-like growth factor (IGF)-1 and insulin. Viability of Rat-1 cell line (Rat-1/ICE) expressing low levels of ICE-LacZ fusion protein is lower than those of cell lines expressing either both Bcl-2 and ICE or mutant ICEGly-->Ser during serum deprivation. Enzymatic activation and processing of ICE are observed in cells induced to die by serum deprivation, which are suppressed by IGF-1. IGF-1 or insulin suppresses ICE-mediated cell death without affecting the expression levels of Bcl-2, Bcl-x, or Bax. Taken together, these results indicate that ICE is activated by growth factor deprivation, and IGF-1 is able to suppress ICE-mediated cell death through a mechanism independent of the expression of Bcl-2, Bcl-x, or Bax.
 ...
PMID:Suppression of interleukin-1 beta-converting enzyme-mediated cell death by insulin-like growth factor. 861 90

Activation of the type I insulin-like growth factor receptor (IGF-IR) blocks osmotic mediated programmed cell death (PCD) in neurons. We speculated that IGF-IR activation could afford neuroprotection either by effecting the negative regulators of the death pathway, Bcl-2 and Bcl-xL, or by altering activity of the ced-3/ICE-like proteases. Here we report that osmotic stress decreases total neuronal Bcl-2 by 4-fold and that hyperosmotic PCD correlates with proteolytic processing of neuronal ced-3/ICE-like proteases. IGF-IR activation maintains normal Bcl-2 levels, and signaling via the IGF-IR:phosphatidylinositol 3-kinase pathway prevents ICE/LAP-3 and Yama/CPP32 processing. Finally, increased neuronal IGF-IR expression enhances the negative death regulator Bcl-xL. We suggest that IGF-IR signaling exerts its short-term inhibitory effects upon PCD "upstream" of both Bcl proteins and ced-3/ICE-like proteases, while chronic increased IGF-IR expression may modulate susceptibility to death signals by mediating the negative death regulator, Bcl-xL.
 ...
PMID:Type I insulin-like growth factor receptor activation regulates apoptotic proteins. 894 17

We examined whether apoptosis is involved in hypoxic cell death using primary cultures of rat cortical neurons and whether the cell death is associated with changes in Bcl-2 and Bax expressions and activities of caspases. Hypoxic insult accelerates apoptosis, as shown by apoptotic nuclei and by chromatin degradation of internucleosomal fragments. This apoptotic process is accompanied by a rapid and sustained down-regulation of Bcl-2, whereas levels of Bax are unchanged. Furthermore, hypoxic insult activates sequentially caspase-1-like and caspase-3-like proteases, following down-regulation of Bcl-2 expression. Peptide inhibitors of either caspase-1 or caspase-3 protect against neuronal death, although they do not prevent hypoxia-induced down-regulation of Bcl-2. Furthermore, treatment of cortical neurons with either insulin-like growth factor-1 (IGF-1) or basic fibroblast growth factor (bFGF), growth factors which are implicated to prevent neuronal loss in ischemic brain, partly prevented neuronal death accompanied by inhibition of alterations in Bcl-2 protein levels and caspase-3-like activities. These results suggest that hypoxia induces neuronal death by down-regulation of Bcl-2 protein levels followed by sequential activation of the caspases, and the protection from neuronal cell death of these growth factors under hypoxic conditions derives at least partly from their capability to prevent down-regulation of the anti-apoptotic protein levels.
 ...
PMID:Roles of Bcl-2 and caspases in hypoxia-induced neuronal cell death: a possible neuroprotective mechanism of peptide growth factors. 968 76

The aim of this study was to quantify spinal cord expression of genes known to cause familial amyotrophic lateral sclerosis (FALS) or influence survival in a large cohort of sporadic cases of ALS (SALS), in order to determine their relevance to pathogenic mechanisms occurring in SALS. The expression of superoxide dismutase 1 (SOD1), vesicle associated membrane protein (VAPB), senataxin (SETX), dynactin (DCTN1), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF1), the small heat shock proteins, HSPB1 and HSPB8, and three genes activated during disease progression, caspases-1 and -3 and glial fibrillary acidic protein (GFAP), were quantified. Robust changes in the expression of four genes were found, VAPB mRNA levels were decreased in the spinal cord of ALS patients compared to controls (p<0.006), whilst HSPB1, HSPB8 and caspase-1 showed significant increases (1.5-2.3-fold). Expression of VAPB mRNA and protein was predominantly localised to large motor neurones further supporting the relevance of this finding to disease progression occurring in SALS.
 ...
PMID:Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord. 1870 Nov 94