Apoptotic pathway in the rat small intestinal mucosa is different between fasting and ischemia-reperfusion

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 291; no. 1; p. 7
• Main Authors: Fujise, Takehiro, Iwakiri, Ryuichi, Wu, Bin, Amemori, Sadahiro
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.07.2006
• Subjects: Apoptosis; Comparative studies; Mitochondrial DNA; Rodents; Small intestine
• ISSN: 0193-1857; 1522-1547

We have previously demonstrated that fasting and ischemia-reperfusion (I/R) induced apoptosis in rat intestinal mucosa. It is widely accepted that apoptosis is induced through two main pathways. This study aimed to compare apoptotic pathways following fasting and hR. Rats were divided into two groups: the hR group involved occlusion of the superior mesenteric artery for 60 mm, followed by 60-mm reperfusion, whereas the fasting group involved fasting for 24 or 48 h. Intestinal apoptosis was assessed as percentage of fragmented DNA, by electrophoresis and by a terminal deoxynucleotidyl transferase mediated dUDP-biotin nick- end labeling (TUNEL) assay. Apoptotic proteins including death ligands/receptors and caspases were evaluated by Western blot analysis. Small intestinal mucosal height and mitochondrial dehydrogenase function were assessed. Fasting and hR significantly induced intestinal apoptosis. Mucosal height was significantly decreased in fasting rats, and mitochondrial dysfunction was induced only by hR. Expressions of Fas, Fas ligand, and TNF-a type 1 receptor were enhanced in fasting and hR rats. After h/R, expressions of cytochrome c and cleaved caspase-9 were significantly increased. In contrast, expressions of cleaved caspase-8 and cleaved caspase-3 increased in fasting rats. Fasting promoted mucosal apoptosis via a receptor-mediated type I apoptotic pathway in the rat small intestine, and hR induced apoptosis via a mitochondria-mediated type II pathway. [PUBLICATION ABSTRACT]