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)

Estrogen plays a critical role in the protection from apoptosis in several cell types because the withdrawal of estrogen leads to increased apoptosis in tissues such as the brain, endothelium, testes, and uterus. Our recent report demonstrated that the chick oviduct also regresses through apoptotic mechanisms during estrogen deficiency. Despite these observations, very little is known concerning the intracellular mechanisms by which estrogen opposes apoptosis. To better understand how estrogen exerts its antiapoptotic effects, several key apoptotic genes were examined for their regulation by estrogen. Our results show that mRNA expression levels of Bcl-2, hsp-70, c-myc, Bcl-X(l), caspase-3, and caspase-6 remain essentially constant when apoptosis is stimulated by estrogen withdrawal. However, the genes for caspase-1 and caspase-2 are rapidly stimulated, at least for the most part, at the transcriptional level after the withdrawal of estrogen. This increase in caspase-2 mRNA is followed by an increase in enzyme activity. Furthermore, although mRNA expression levels are unaffected, both caspase-3 and caspase-6 proenzymes are activated in the estrogen-withdrawn cells. Taken together, these results demonstrate that estrogen has the potential to oppose apoptosis by regulating caspase activity through both transcriptional and posttranscriptional mechanisms in reproductive tissues.
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PMID:Tissue-protective effects of estrogen involve regulation of caspase gene expression. 1204 18

Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.
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PMID:Gene expression profiling of p53(+/-) knockout and wild-type mice following diethylstilbestrol administration. 1554 18

The mechanism of action, leakage of cytochrome c from mitochondria into cytosol, for the antineoplastic compound glyfoline was examined. Additionally, our current studies revealed that glyfoline induced apoptotic changes and arrested cell cycle procession at the G2/M phase in nasopharyngeal carcinoma (NPC). A reverse transcriptase polymerase chain reaction (RT-PCR) showed no specific changes of apoptosis-related gene expression (i. e., bax, ICE-alpha,beta, bcl-2, and c-myc). However, no similar changes were detected in fibroblasts and peripheral lymphocytes after glyfoline treatment suggesting that glyfoline has a higher affinity for tumor cells than for normal cells.
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PMID:Cytochrome C release induces apoptosis of nasopharyngeal carcinoma (NPC) by antitumor glyfoline. 1567 70


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