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Differential Effects of Luminal Arginine and Glutamine on Metalloproteinase Production in the Postischemic Gut
Author(s) -
Robinson Emily K.,
Kelly Daniel P.,
Mercer David W.,
Kozar Rosemary A.
Publication year - 2008
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607108319806
Subject(s) - matrix metalloproteinase , arginine , glutamine , nitric oxide synthase , nitric oxide , jejunum , endocrinology , medicine , citrulline , downregulation and upregulation , gelatinase , chemistry , biology , biochemistry , amino acid , gene
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.