Hypochlorous acid mobilizes cellular zinc

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Abstract
Neutrophil oxidants, in particular hypochlorous acid (HOCl), can cause injury to healthy tissues at sites of inflammation. Some of this injury may be caused by oxidant-induced mobilization of metals. We examined the ability of HOCl to mobilize Zn2+ in target tissues. Arterial endothelial cell cultures and heart tissue sections were incubated for 90 s in buffered saline, pH 7.3, containing a suspension of N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (100 nmol/mL), a Zn2+-specific fluorescent chelator, and were subsequently exposed to 200 μM HOCl for 5 min. The cellular fluorescence was analyzed histologically and showed a marked increase in intensity after HOCl treatment, which was indicative of an increase in cellular free Zn2+ concentration. Incubation of HOCl-treated tissues with dithiothreitol, a membrane-permeable metal chelator, caused a sharp decline in cellular fluorescence. This study shows for the first time that HOCl can mobilize cellular Zn2+. In view of the multiple cellular roles played by Zn2+, its mobilization by oxidants at sites of inflammation may contribute to the observed injury. The ability of dithiothreitol to chelate the mobilized Zn2+ suggests that it may be able to reverse Zn2+-mediated injury.Key words: hypochlorous acid, zinc mobilization, dithiothreitol, neutrophil oxidants, N-(6-methoxy-8-quinolyl)-p-toluene-sulfonamide.

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