title: Hypochlorous acid-induced mobilization of zinc from metalloproteins.
abstract: Hypochlorous acid (HOCl), a neutrophil oxidant, can contribute to tissue injury at sites of inflammation by its reactivity with protein sulfhydryls. The present study shows that physiological concentrations (50-200 microM) of HOCl can displace Zn2+ from metalloproteins, such as metallothionein and alcohol dehydrogenase, in which the metal is bound to sulfhydryls by means of thiolate (S-Zn) bonds. No mobilization of Zn2+ was observed from superoxide dismutase in which the metal is not bound to cysteine, suggesting that HOCl reacts selectively with thiolate bonds. Zn2+ mobilization, measured spectrophotometrically with the metallochromic indicator 4-(2-pyridylazo)resorcinol, was also observed from complexes of this metal with other thiol-containing compounds such as 2,3-dimercaptopropanol and metallothionein fragment 56-61. HOCl cleavage of the thiolate bonds was confirmed by the decrease in absorbance at 250 nm. This study shows for the first time that HOCl can mobilize protein-bound Zn2+ and suggests that neutrophil oxidant injury may be partially mediated by the mobilization of cellular Zn2+.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Fliss
authors.forename: M
authors.initials: M
authors.lastname: Ménard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006736:Horses; D006997:Hypochlorous Acid / Q000378:metabolism*; D007700:Kinetics; D008667:Metalloproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D012118:Resorcinols / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D008667:Metalloproteins; D009842:Oligopeptides; D012118:Resorcinols; D006997:Hypochlorous Acid; D015032:Zinc; C028398:4-(2-pyridylazo)resorcinol