Submitted on August 23, 2005
Accepted on March 12, 2006
Apoptotic pathway in the rat small intestinal mucosa is different between fasting and ischemia-reperfusion
Takehiro Fujise1, Ryuichi Iwakiri1, Wu Bin1, Sadahiro Amemori2, Takashi Kakimoto1, Fumie Yokoyama1, Yasuhisa Sakata1, Seiji Tsunada1, and Kazuma Fujimoto1*
1 Internal Medicine, Saga Medical School, Saga, Japan
2 Internal Medicine, Saga Medical School, Malaysia
* To whom correspondence should be addressed. E-mail: fujimoto{at}med.saga-u.ac.jp.
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; while the fasting group involved fasting for 24 or 48 h. Intestinal apoptosis was assessed as % fragmented DNA, by electrophoresis, and by a TUNEL assay. Apoptotic proteins including death ligands/receptors, 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, FasL and TNFR1 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 receptor-mediated type I apoptotic pathway in the rat small intestine, and I/R induced apoptosis via mitochondria-mediated type II pathway.
