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

Am J Physiol Gastrointest Liver Physiol. 2006 Jul;291(1):G110-6. doi: 10.1152/ajpgi.00393.2005. Epub 2006 Mar 30.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism*
  • Cells, Cultured
  • Cytokines / metabolism*
  • Fasting / metabolism*
  • Intestinal Mucosa / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Signal Transduction

Substances

  • Apoptosis Regulatory Proteins
  • Cytokines