Apoptotic pathway in the rat small intestinal mucosa is different between fasting and ischemia-reperfusion.
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.
Department of Intestinal Medicine, Saga Medical School, Saga 849-8501, Japan.
Takehiro
T
Fujise
Ryuichi
R
Iwakiri
Bin
B
Wu
Sadahiro
S
Amemori
Takashi
T
Kakimoto
Fumie
F
Yokoyama
Yasuhisa
Y
Sakata
Seiji
S
Tsunada
Kazuma
K
Fujimoto
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction
D051017:Apoptosis Regulatory Proteins; D016207:Cytokines