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Peroxynitrite increases arginase expression in endothelial cells: An effect mimicked by preeclamptic plasma
Author(s) -
Sankaralingam Sowndramalingam,
Davidge Sandra T
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a291-a
Subject(s) - arginase , peroxynitrite , nitrotyrosine , nitric oxide , preeclampsia , chemistry , ornithine , endocrinology , arginine , medicine , nitric oxide synthase , biochemistry , superoxide , biology , enzyme , pregnancy , genetics , amino acid
Preeclampsia is characterized by hypertension and proteinuria occurring after the 20th week of gestation. Decreased nitric oxide (NO) bioavailability could be one of the causative factors in the pathogenesis of preeclampsia. In addition to scavenging of NO by superoxide to form peroxynitrite, another mechanism for reduced NO bioavailability may be through increased arginase activity. Arginase catalyzes the conversion of L‐arginine to L‐ornithine and urea. As arginase and NO synthase compete for L‐arginine, up regulation of arginase could decrease L‐arginine bioavailability and decrease NO formation. We hypothesized that circulating factors in preeclamptic plasma will increase peroxynitrite in endothelial cells and result in a feed forward mechanism to up regulate arginase. HUVECs were incubated with SIN‐1 (0.25 mM), a peroxynitrite donor for 12 hours or 2% plasma from either normotensive pregnant (Preg, n=3) or preeclamptic (PE, n=3) women for 24 hours. Nitrotyrosine staining, a marker of peroxynitrite formation and arginase II protein expression were assessed. PE plasma increased nitrotyrosine staining in endothelial cells 6 fold when compared to Preg plasma. SIN‐1 increased arginase II protein expression by ~ 180% (P<0.01) when compared to untreated cells as assessed by western blot. PE plasma increased arginase II protein expression when compared to Preg plasma (P<0.05). Circulating factors in preeclamptic plasma increase arginase expression likely via generation of peroxynitrite which further provides a feed forward mechanism to up regulate arginase. Funded by CIHR.