Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preclinical and clinical studies have demonstrated that a free radical scavenger edaravone has neuroprotective effects on ischemic stroke but the underlying mechanism is not fully understood. The aim of this research is to explore the effect of edaravone on the apoptotic process involving the Fas/FasL signaling pathway. Transient focal ischemia in rats was induced for 2 hours by middle cerebral artery occlusion (MCAO). After reperfusion rats were treated i.v. with either edaravone or physiological saline. The expression of Fas-associated death domain protein (FADD), death-associated protein (Daxx) and caspase-8 was examined by immunohistochemistry. The mRNA levels for FADD and Daxx by reverse-transcriptase PCR (RT-PCR) and apoptosis was assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Neurological scores and infarction volumes were also evaluated. Edaravone significantly improved the neurological outcome (p<0.05) and reduced the total infarct volumes (p<0.05), compared with saline control. In addition, edaravone-treatment significantly reduced the number of TUNEL-positive cells (p<0.01), reduced expression levels of FADD, Daxx and caspase-8 immunoreactivity (p <0.05 approximately 0.01), and decreased mRNA levels of FADD and Daxx (p<0.05 approximately 0.01) within the peri-infarct area. We conclude that edaravone may protect ischemic neurons from apoptosis via suppressing the gene expression of the Fas/FasL signaling pathway.
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PMID:Edaravone neuroprotection effected by suppressing the gene expression of the Fas signal pathway following transient focal ischemia in rats. 1796 39

The aim of this study was to investigate the changes of expression of Fas-associated proteins and its cellular localization in the peri-infarct region following transient focal cerebral ischemia. Adult male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAo) for 2 h and reperfusion for 1, 3, 6, 12 and 24 h. The expression of Fas-associated death domain protein (FADD), Fas-associated phosphatase-1 (FAP-1) caspase-8 and death-associated protein (Daxx), the pro-apoptotic genes, were examined by methods of RT-PCR, immunohistochemistry and Western blot. The results showed that the expression levels of mRNA and protein for FADD and caspase-8 increased significantly at 1-3 h after reperfusion, peaked at 12 h, then declined markedly at 24 h. The time course change of FAP-1 was consistent with that of FADD. The expression level of mRNA and protein for death-associated protein (Daxx) increased significantly at 3 h after reperfusion and persisted for 24 h at a high level. Immunofluorescence double-staining laser scanning showed that the immunoreactivity of FADD was localized in cytoplasm, and Daxx immunoreactivity was translocated from nucleus to cytoplasm at 3 h after reperfusion. The TUNEL-positive cells could be found in peri-infarct region at 3 h and increased with time after reperfusion. Our findings suggest a possible association between expression of FADD, caspase-8, Daxx and FAP-1 genes and apoptosis following ischemia.
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PMID:Expression and localization of Fas-associated proteins following focal cerebral ischemia in rats. 1809 38