iNOS enhances rat intestinal apoptosis after ischemia-reperfusion
Autor: | Akifumi Ootani, Bin Wu, Seiji Tsunada, Kazuma Fujimoto, Takehiro Fujise, Masataka Kojima, Hiroyoshi Utsumi, Ryuichi Iwakiri |
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Rok vydání: | 2002 |
Předmět: |
Male
Cytochrome Free Radicals Blotting Western Nitric Oxide Synthase Type II Caspase 3 Apoptosis Cytochrome c Group DNA Fragmentation Mitochondrion Nitric Oxide Biochemistry Epithelium Rats Sprague-Dawley Intestinal mucosa Physiology (medical) medicine Animals Enzyme Inhibitors Electrophoresis Agar Gel biology Cytochrome c medicine.disease Molecular biology Immunohistochemistry Mitochondria Rats Nitric oxide synthase Jejunum Caspases Reperfusion Injury biology.protein Nitric Oxide Synthase Reperfusion injury |
Zdroj: | Free radical biologymedicine. 33(5) |
ISSN: | 0891-5849 |
Popis: | The aim of this study was to demonstrate (i) the role of iNOS (inducible nitric oxide synthase) on apoptosis in the rat intestinal mucosa after ischemia-reperfusion, and (ii) the effect of iNOS on the release of cytochrome c from mitochondria. The superior mesenteric artery was occluded for 60 min and was followed by a 60 min reperfusion. Rats were pretreated with an intraperitoneal injection of the following iNOS inhibitors: N-nitro- l -arginine methyl ester, aminoguanidine, and (1S,5S,6R,7R)-7- chloro-3-imino-5-methyl-2-azabicyclo [4. 1. 0] heptane hydrochloride (ONO-1714). Apoptosis was evaluated and NOX in the portal vein was assayed. The amount of iNOS, caspase-3, and cytochrome c were determined by a Western blot analysis. Intestinal mucosal epithelial mitochondrial dehydrogenase activity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoilium bromide. Ischemia-reperfusion increased intestinal mucosal apoptosis, NOX production in the portal vein, the amount of iNOS protein, and the release of cytochrome c, but not caspase-3. Inhibitors of iNOS significantly attenuated the induction of apoptosis, increased NOX production, and release of cytochrome c. Mitochondrial dysfunction was induced by ischemia-reperfusion, which was ameliorated by iNOS inhibitors. Our results indicate that iNOS is related to increased mucosal apoptosis in the rat small intestine after ischemia-reperfusion, which is partly explained by the release of cytochrome c from mitochondria to cytosols following mitochondrial dysfunction. |
Databáze: | OpenAIRE |
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