Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

摘要

Chronic inflammation results in increased nitrogen monoxide (⋅NO) formation and the accumulation of nitrite (NO\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}_{2}^{-}\end{equation*}\end{document}). 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\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}_{2}^{-}\end{equation*}\end{document} but not nitrate (NO\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}_{3}^{-}\end{equation*}\end{document}) substantially decreased HOCl-dependent cellular toxicity even when NO\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}_{2}^{-}\end{equation*}\end{document} was added at low (μM) concentrations. In contrast, NO\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}_{2}^{-}\end{equation*}\end{document} alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}_{2}^{-}\end{equation*}\end{document} 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\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}_{2}^{-}\end{equation*}\end{document} to give nitryl chloride (NO2Cl), which is less damaging in our cell system.