Proteomic analysis of intestinal ischemia/reperfusion injury and ischemic preconditioning in rats reveals the protective role of aldose reductase.
Intestinal ischemia/reperfusion (I/R) injury is a critical condition associated with high morbidity and mortality. Studies show that ischemic preconditioning (IPC) can protect the intestine from I/R injury. However, the underlying molecular mechanisms of this event have not been fully elucidated. In the present study, 2-DE combined with MALDI-MS was employed to analyze intestinal mucosa proteomes of rat subjected to I/R injury in the absence or presence of IPC pretreatment. The protein content of 16 proteins in the intestinal mucosa changed more than 1.5-fold following intestinal I/R. These proteins were, respectively, involved in the cellular processes of energy metabolism, anti-oxidation and anti-apoptosis. One of these proteins, aldose reductase (AR), removes reactive oxygen species. In support of the 2-DE results, the mRNA and protein expressions of AR were significantly downregulated upon I/R injury and enhanced by IPC as confirmed by RT-PCR and western blot analysis. Further study showed that AR-selective inhibitor epalrestat totally turned over the protective effect of IPC, indicating that IPC confers protection against intestinal I/R injury primarily by increasing intestinal AR expression. The finding that AR may play a key in intestinal ischemic protection might offer evidences to foster the development of new therapies against intestinal I/R injury.
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China. liukexuan807@yahoo.com.cn
Ke-Xuan
KX
Liu
Cai
C
Li
Yun-Sheng
YS
Li
Bao-Long
BL
Yuan
Miao
M
Xu
Zhengyuan
Z
Xia
Wen-Qi
WQ
Huang
D000449:Aldehyde Reductase / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D004734:Energy Metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply / Q000378:metabolism*; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation; D008297:Male; D020556:Neutrophil Infiltration; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
D020543:Proteome; D000449:Aldehyde Reductase