Effect of lead on the erythrocyte (Ca2+,Mg2+)-ATPase activity. Calmodulin involvement.
I have investigated the effect of lead on the erythrocyte ghosts (Ca2+,Mg2+)-ATPase, with special attention to the role of calmodulin in this phenomena. Under regular incubation conditions, lead inhibits the enzyme with an IC50 of 6.0 microM. The presence of exogenously added calmodulin apparently does not change this inhibitory value. DTT added during the incubation period does not affect the inhibitory action of lead. However, when the membranes are preincubated with DTT, an important IC50 displacement is observed, either with or without added calmodulin. Since [125I]calmodulin binding to the membranes is enhanced when lead is used, the possibility of a lead/calmodulin complex that optimally stimulates the enzyme using lead concentrations between 1.0 and 10.0 microM, is suggested. Based on the experimental data, I propose two well defined actions of lead; first, an inhibitory action upon the ATPase above 1.0 microM lead, most probably related to essential sulphydryl groups in the enzyme; and second, a direct action of lead upon calmodulin at lead concentrations below 1.0 microM.
Mas-Oliva
J
J
Departamento de Bioenergética, Universidad Nacional Autónoma de México, D.F.
D000255:Adenosine Triphosphate / Q000502:physiology; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000097:blood*; D002118:Calcium / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000097:blood*; D002147:Calmodulin / Q000502:physiology*; D004229:Dithiothreitol / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007854:Lead / Q000494:pharmacology*; D008628:Mercury / Q000494:pharmacology
D002147:Calmodulin; D007854:Lead; D000255:Adenosine Triphosphate; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D008628:Mercury; D002118:Calcium; D004229:Dithiothreitol