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L‐Arginine Enhances Nitrative Stress and Exacerbates TNF‐Alpha Toxicity in Endothelial Cells
Author(s) -
Xia Zhengyuan,
Liu Huimin,
Wang Fang,
Luo Tao,
Xia Zhongyuan,
Irwin Michael G,
Vanhoutte Paul M
Publication year - 2009
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.23.1_supplement.936.2
Subject(s) - peroxynitrite , nitric oxide , tumor necrosis factor alpha , arginine , apoptosis , nitrotyrosine , endothelial stem cell , chemistry , umbilical vein , nitric oxide synthase , medicine , endocrinology , superoxide , pharmacology , biochemistry , enzyme , amino acid , in vitro
Supplementation of L‐arginine, a nitric oxide precursor, during the late phase of myocardial ischemia/reperfusion (MI/R) increases myocyte apoptosis and exacerbates myocardial injury. Apoptosis of the endothelial cells precedes that of the cardiomyocytes during MI/R, and this is associated with increased tumor necrosis factor‐alpha (TNF) production. We postulated that L‐arginine may exacerbate TNF induced endothelial cell apoptosis by enhancing nitrative stress. Cultured human umbilical vein endothelial cells were studied under control conditions or treated with TNF alone or in the presence of L‐arginine the non‐selective nitric oxide synthase inhibitor N (omega)‐nitro‐L‐arginine (L‐NNA), propofol (scavenger of peroxynitrite), or L‐arginine plus propofol, respectively, for 24 hours. TNF increased endothelial cell apoptosis, increased the intracellular superoxide production and the protein expression of nitrotyrosine, a footprint of peroxynitrite formation and an index of nitrative stress. L‐arginine exacerbated all these changes while L‐NNA or propofol attenuated them. Thus, under pathological conditions associated with increased TNF production, L‐arginine supplementation may further exacerbate TNF cellular toxicity by enhancing nitrative stress. Supported by a Society of Cardiovascular Anesthesiologists Research Starter Grant (to ZX).