Platelet-activating factor promotes mucosal apoptosis via FasL-mediating caspase-9 active pathway in rat small intestine after ischemia-reperfusion.
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.
Wu
Bin
B
Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Iwakiri
Ryuichi
R
Ootani
Akifumi
A
Fujise
Takehiro
T
Tsunada
Seiji
S
Fujimoto
Kazuma
K
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D017209:Apoptosis; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D010972:Platelet Activating Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016753:Interleukin-10; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases