Effect of massive small bowel resection on the Bax/Bcl-w ratio and enterocyte apoptosis.
Following small bowel resection (SBR), the remnant intestine undergoes adaptation. Enterocyte proliferation is increased and counterbalanced by increased rates of apoptosis. To elucidate a mechanism for increased enterocyte apoptosis, this study tested the hypothesis that the ratio between pro-apoptotic Bax and pro-survival Bcl-w correlates with the apoptosis that occurs following SBR. Mice (C57Bl/6; n = 76) underwent a 50% proximal SBR or sham operation. After 12 hours and 1, 2, 3, and 7 days, the ileum was removed, the apoptotic index (apoptotic bodies/crypt) was recorded, and the messenger RNA and protein for Bax and Bcl-w were quantified. The apoptotic index was equivalent in the sham and SBR mice at 12 hours; however, it was significantly elevated following SBR at every other day measured. The ratio of Bax to Bcl-w messenger RNA relative to sham operation increased after SBR at 24 hours, decreased by day 3, and returned to baseline levels by 1 week. The protein ratio showed an increase by day 1, which remained elevated through day 7. An augmented ratio of Bax to Bcl-w messenger RNA and protein corresponded with the increase in enterocyte apoptosis. Alterations in the expression ratio of these genes may play a role in establishing a new homeostatic set point between proliferation and apoptosis during adaptation.
Stern
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LE
Division of Pediatric Surgery, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
Falcone
R A
RA
Kemp
C J
CJ
Stuart
L A
LA
Erwin
C R
CR
Warner
B W
BW
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D020895:Enterocytes / Q000502:physiology*; D007082:Ileum / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012778:Short Bowel Syndrome / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
D051017:Apoptosis Regulatory Proteins; C494827:Bax protein, mouse; C101155:Bcl2l2 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein