Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

doi:10.1073/pnas.152462399

Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

^*Department of Biochemistry, Faculty of Medicine, National University of Singapore, 10 Kent Ridge Crescent, Republic of Singapore 119260; and ^‡Department of Immunology and Microbiology, Thomas Jefferson University, Philadelphia, PA 19107

Contributed by Hilary Koprowski

Abstract

Chronic inflammation results in increased nitrogen monoxide (⋅NO) formation and the accumulation of nitrite (NO $\text{[math]}$ ). 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 $\text{[math]}$ but not nitrate (NO $\text{[math]}$ ) substantially decreased HOCl-dependent cellular toxicity even when NO $\text{[math]}$ was added at low (μM) concentrations. In contrast, NO $\text{[math]}$ alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO $\text{[math]}$ 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 $\text{[math]}$ to give nitryl chloride (NO₂Cl), which is less damaging in our cell system.

Footnotes

↵ † To whom reprint requests should be addressed. E-mail: bchwml{at}nus.edu.sg.
Abbreviations:
1. MPO, myeloperoxidase
2. HOCl, hypochlorous acid
3. GSH, reduced glutathione
4. NO $\text{[math]}$ , nitrite
5. NO $\text{[math]}$ , nitrate
6. LDH, lactate dehydrogenase
7. NO₂Cl, nitryl chloride