Submitted on May 31, 2005
Accepted on October 7, 2005
DIFFERENTIAL INDUCTION OF PPAR
BY LUMINAL GLUTAMINE AND iNOS BY LUMINAL ARGININE IN THE RODENT POST ISCHEMIC SMALL BOWEL
N. Sato1, F. A. Moore1, B. C. Kone2, L. Zou2, M. A. Smith1, M. A. Childs1, Olufemi-Moore1, S. G. Schultz3, and R. A. Kozar1*
1 Department of Surgery, University of Texas-Houston School of Medicine, Houston, TX, USA
2 Department of Medicine, University of Texas-Houston School of Medicine, Houston, TX, USA
3 Department of Integrative Biology and Pharmacology, University of Texas-Houston School of Medicine, Houston, TX, USA
* To whom correspondence should be addressed. E-mail: Rosemary.A.Kozar{at}uth.tmc.edu.
Using a rodent model of gut ischemia/ reperfusion (IR), we have previously shown that the induction of iNOS is harmful while the induction of HO-1 and PPAR-gamma is protective. In the present study, we hypothesized that the luminal nutrients, arginine and glutamine, differentially modulate these molecular events in the post ischemic gut. Jejunal sacs were created in rats at laparotomy and filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 minutes of superior mesenteric artery occlusion and 6 hours of reperfusion and compared to shams. Jejunum was harvested for histology or myeloperoxidase activity (MPO, inflammation). Heat shock proteins and iNOS were quantitated by Western Blot analysis and PPAR
by DNA binding activity. In some experiments, rats were pretreated with the PPAR inhibitor, G9662, or with the iNOS inhibitor,1400W. iNOS, was significantly increased by arginine but not glutamine following gut IR and was associated with increased MPO activity and mucosal injury. On the other hand, PPAR, was significantly increased by glutamine but decreased by arginine while heat shock proteins were similarly increased in all experimental groups. The PPAR inhibitor, G9662, abrogated the protective effects of glutamine while the iNOS inhibitor,1400W, attenuated the injurious effects of arginine. We concluded that luminal arginine and glutamine differentially modulate the molecular events that regulate injurious IR-mediated gut inflammation and injury. The induction of PPAR by luminal glutamine is a novel protective mechanism while luminal arginine appears harmful to the post ischemic gut due to enhanced expression of iNOS.
