Inhibition of hypochlorous acid-induced cellular toxicity by nitrite.
Chronic inflammation results in increased nitrogen monoxide (.NO) formation and the accumulation of nitrite (NO(2-)). Neutrophils stimulated by various inflammatory mediators release myeloperoxidase to produce the cytotoxic agent hypochlorous acid (HOCl). Exposure of chondrocytic SW1353 cells to HOCl resulted in a concentration- and time-dependent loss in viability, ATP, and glutathione levels. Treatment of cells with NO(2-) but not nitrate (NO(3-)) substantially decreased HOCl-dependent cellular toxicity even when NO(2-) was added at low (microM) concentrations. In contrast, NO(2-) alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO(2-) accumulation at chronic inflammatory sites, where both HOCl and.NO are overproduced, may be cytoprotective against damage caused by HOCl. We propose that this is because HOCl is removed by reacting with NO(2-) to give nitryl chloride (NO2Cl), which is less damaging in our cell system.
Whiteman
Matthew
M
Department of Biochemistry, Faculty of Medicine, National University of Singapore, 10 Kent Ridge Crescent, Republic of Singapore 119260. bchwml@nus.edu.sg
Hooper
D Craig
DC
Scott
Gwen S
GS
Koprowski
Hilary
H
Halliwell
Barry
B
D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism / Q000494:pharmacology*
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D006997:Hypochlorous Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; C445660:nitryl chloride