Platelet activating factor promotes mucosal apoptosis via FasL mediating caspase-9 active pathway in rat small intestine after ischemia-reperfusion

被引:34
作者
Wu, B [1 ]
Iwakiri, R [1 ]
Ootani, A [1 ]
Fujise, T [1 ]
Tsunada, S [1 ]
Fujimoto, K [1 ]
机构
[1] Saga Med Sch, Dept Internal Med & Gastrointestinal Endoscopy, Div Gastroenterol, Saga 8498501, Japan
关键词
platelet activating factor acetylhydrolase; platelet endothelial cell adhesion; molecule-1; interleukin-6; Bid; cytochrome c;
D O I
10.1096/fj.02-0499fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Platelet activating factor (PAF) is a proinflammatory lipid mediator for inflammatory response. It is unclear whether PAF is involved in the very complex process of ischemia-reperfusion (I/R) induced mucosal apoptosis in small intestine. Intestinal I/R was induced in rats intestine by 60 min occlusion of the superior mesenteric artery, followed by a 60 min reperfusion. I/R induced mucosal apoptosis and PAF activity but inhibited PAF-acetylhydrolase activity. Increases in interleukin-6 (IL-6) and decreases in IL-10 were observed. Western blot analysis showed that I/R induced expressions of platelet endothelial cell adhesion molecule-1 (PECAM-1) and Fas and Fas ligand (FasL) proteins, cleaved Bid, and enhanced the release of cytochrome c from mitochondria to activate caspase-9. Pretreatment of PAF antagonist BN-52021 attenuated these changes, except the increase in Fas. The results showed that I/R-inhibited mucosal PAF-acetylhydrolase activity resulted in an increase of activated PAF. The activated PAF increased the mucosal IL-6 and PECAM-1, enhanced the expression of FasL but not Fas, and led to the cleavage of Bid and the release of cytochrome c from mitochondria to activate caspase-9. This finding suggests that PAF promotes mucosal apoptosis after I/R in the rat small intestine partly through FasL mediating caspase-9 active pathway.
引用
收藏
页码:1156 / +
页数:17
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