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Am J Physiol Gastrointest Liver Physiol 291: G110-G116, 2006. First published March 30, 2006; doi:10.1152/ajpgi.00393.2005
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MUCOSAL BIOLOGY

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

Takehiro Fujise, Ryuichi Iwakiri, Bin Wu, Sadahiro Amemori, Takashi Kakimoto, Fumie Yokoyama, Yasuhisa Sakata, Seiji Tsunada, and Kazuma Fujimoto

Department of Internal Medicine, Saga Medical School, Saga, Japan

Submitted 23 August 2005 ; accepted in final form 12 March 2006

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 I/R. Rats were divided into two groups: the I/R group involved occlusion of the superior mesenteric artery for 60 min, followed by 60-min 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 I/R significantly induced intestinal apoptosis. Mucosal height was significantly decreased in fasting rats, and mitochondrial dysfunction was induced only by I/R. Expressions of Fas, Fas ligand, and TNF-{alpha} type 1 receptor were enhanced in fasting and I/R rats. After I/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 I/R induced apoptosis via a mitochondria-mediated type II pathway.

apoptosis; mitochondrial function; homeostasis; feeding



Address for reprint requests and other correspondence: K. Fujimoto, Dept. of Intestinal Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan (e-mail: fujimoto{at}med.saga-u.ac.jp)







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