Differential effects of luminal arginine and glutamine on metalloproteinase production in the postischemic gut.
BACKGROUND
Matrix metalloproteinases (MMPs) are a group of endopeptidases induced under inflammatory conditions in the intestine which possess the capacity to degrade components of the extracellular matrix. We have previously demonstrated that MMP-2 expression correlates with increased inducible nitric oxide synthase (iNOS) production in the stomach and that iNOS is upregulated in the postischemic gut by the luminal nutrient arginine and repressed by luminal glutamine. We therefore hypothesized that arginine would enhance expression of MMP-2 in the postischemic gut.


METHODS
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 (SMAO) and 6 hours of reperfusion and compared with shams. Jejunum was harvested, and membrane type-1 matrix metalloproteinase (MT1-MMP), MMP-2, and iNOS protein expression was determined by Western analysis and MMP-9 production by gelatin zymography.


RESULTS
MMP-2, MT1-MMP, MMP-9, and iNOS were all increased after SMAO compared with shams. Arginine maintained while glutamine inhibited the increase in iNOS, MT1-MMP, and MMP-2 expression in the postischemic gut. Pretreatment of the arginine group with a selective iNOS inhibitor blunted the induction of MMP-2 in the postischemic gut. There was no differential modulation of MMP-9 by the luminal nutrients.


CONCLUSIONS
The arginine-induced upregulation of iNOS may contribute to increased activity of MT1-MMP and MMP-2. The mechanism for this differential regulation by arginine warrants further investigation.
Robinson
Emily K
EK
Department of Surgery, University of Texas-Houston Health Science Center, Houston, TX 77030, USA. emily.k.robinson@uth.tmc.edu
Kelly
Daniel P
DP
Mercer
David W
DW
Kozar
Rosemary A
RA
D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D004750:Enteral Nutrition; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology*; D007583:Jejunum / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*
D005973:Glutamine; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D045726:Metalloproteases; D020778:Matrix Metalloproteinase 2