title: 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 Zn(2+)-specific fluorescent chelator, and were subsequently exposed to 200 microM 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 Zn(2+)-mediated injury.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Ottawa, Ont., Canada.
authors.forename: H
authors.initials: H
authors.lastname: Fliss
authors.forename: M
authors.initials: M
authors.lastname: Ménard
authors.forename: M
authors.initials: M
authors.lastname: Desai
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005456:Fluorescent Dyes; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000494:pharmacology; D014105:Tosyl Compounds; D015032:Zinc / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D002412:Cations; D002614:Chelating Agents; D005456:Fluorescent Dyes; D013449:Sulfonamides; D014105:Tosyl Compounds; D006997:Hypochlorous Acid; C061730:N-(6-methoxy-8-quinolyl)-4-toluenesulfonamide; D015032:Zinc