Hypochlorous acid mobilizes cellular zinc

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.