Inhibition of human erythrocyte Ca2+-ATPase by Zn2+.
Recent investigations suggest that Ca2(+)-ATPase from fish gills is very sensitive to Zn2+ (Hogstrand et al., 1996. Am. J. Physiol. 270, R1141-R1147). The effect of free Zn2+ ion on the human erythrocyte plasma membrane Ca2(+)-ATPase was investigated to explore the possible extension of this finding to humans. Membrane vesicles were prepared and the Ca2(+)-ATPase activity was measured as Ca2(+)-stimulated ATP hydrolysis and as ATP-dependent Ca2+ transport. The Zn2+ ion inhibited the erythrocyte Ca2(+)-ATPase by reducing Vmax and increasing the K0.5. While in the Ca2+ transport assay only the Vmax was affected at lower Zn2+ concentrations (50-100 pM), reduction of Vmax was always accompanied by an affinity decrease in the ATP hydrolysis assay. The Ca2(+)-ATPase was found to be inhibited by Zn2+ at extremely low concentrations. The IC10 and IC50 for Zn2+, at a Ca2+ concentration of 1.0 microM, were estimated at 4 and 80 pM, respectively. Although the Ca2(+)-ATPase might be more sensitive in vitro than in vivo conditions, the results suggest that physiological concentrations of Zn2+ may reduce the activity of the erythrocyte Ca2(+)-ATPase. Furthermore, disturbance of Ca homeostasis may be a mechanism causing Zn toxicity during exposure.
Hogstrand
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T.H. Morgan School of Biological Sciences, University of Kentucky, Lexington 40506-0225, USA. hogstra@pop.uky.edu
Verbost
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Wendelaar Bonga
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D000255:Adenosine Triphosphate / Q000097:blood; D001693:Biological Transport, Active; D017301:Ca(2+) Mg(2+)-ATPase / Q000097:blood; D002118:Calcium / Q000097:blood; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000097:blood; D002413:Cations, Divalent; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000097:blood; D015032:Zinc / Q000494:pharmacology*
D002413:Cations, Divalent; D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D015032:Zinc; D002118:Calcium