title: [Impact of stress response genes induced by L-glutamine on warm ischemia and reperfusion injury in the rat small intestine].
abstract: L-Glutamine (Gln) is known to have protective effect on the small intestine under deleterious stressful condition. Although the mechanism by which Gln confers intestinal cellular protection remains unclear, its potential role may be mediated via signal transduction including stress response genes and anti-apoptotic genes. Herein, we examined a possible role of stress response genes in warm ischemically injured small intestines. We measured mRNA and protein expression of heme oxygenase (HO)-1, Bcl-2 and Bax at different time points after Gln administration. Warm ischemia model was made by clamping of the superior mesenteric artery for 60 min. After reperfusion, tissue samples were taken for end labeling of nuclear DNA fragments (TdT-mediated d-uridine triphosphate biotin nick end labeling; TUNEL) and hematoxylin-eosin staining. In Gln-treated group, the substantial expression of HO-1 mRNA peaked at 3 h and reduced thereafter, while HO-1 protein synthesis was noted within 3 h and reached plateau thereafter. NO-1-positive components were markedly detected in the villus epithelial cells and crypts. The ratios of Bcl-2/Bax mRNA expression after Gln administration peaked at 3 h and reduced thereafter until 24 h. Bcl-2 immunoreactive protein was enhanced in Gln group, whereas Bax was faintly detected. Following reperfusion, less TUNEL-positive staining of the top of the villi and more prompt recovery of denuded villus epithelial cells were noted in Gln group, compared with those in untreated and lactated Ringer-treated control groups. In conclusion, a concomitant expression of anti-oxidative HO-1 and anti-apoptotic Bcl-2 molecules induced by non-toxic amino acid, Gln, may alleviate or even prevent intestinal warm ischemia and reperfusion injury, attenuating programmed cell death and promoting its reepithelialization.
authors.affiliation: Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Masuko
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D005973:Glutamine / Q000494:pharmacology / Q000627:therapeutic use*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism*; D007511:Ischemia / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D005973:Glutamine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1