Inhibition mechanisms of aluminium are different on the plasma membrane and the sarcoplasmic reticulum calcium pump

DE SAUTU, MARILINA; FERREIRA GOMES, MARIELA; ROLANDO C ROSSI; ROSSI JUAN PABLO F.C.

Salto, República Oriental del Uruguay

Congreso; Latin American Crosstalk In Biophysics And Physiology; 2015

Aluminium (Al3+) is involved with the pathophysiology of neurodegenerative disorders, such as Parkinsonism dementia and Alzheimer?s disease. The action of Al3+ toxicity is linked to changes in the cellular calcium homeostasis, placing the transporting calcium pumps as potential targets. However, it has not been demonstrate that aluminium inhibits any transmembrane transporter of mono and divalent metals. The aim of this work was to study the molecular inhibitory mechanism of Al3+ on Ca2+-ATPases like the plasma membrane (PMCA) and the sarcoplasmic reticulum (SERCA). These P-ATPases transport actively Ca2+. For this purpose, we performed enzymatic measurements of the effect of Al3+ on purified preparations of PMCA and SERCA. Our results show that: (1) Al3+ inhibits Ca2+-ATPase activity of both enzymes with similar apparent affinity; (2) in the presence of Al3+, the apparent affinity for Ca2+ of SERCA decreased, but not for PMCA; (3) Al3+ decreased the apparent affinity for Mg2+ of PMCA; (4) Al3+ increases the phosphorylated intermediate (EP) of PMCA while it has not effect on SERCA; (5) pH does not modify significantly the apparent inhibitory affinity for Al3+ for both PMCA and SERCA. This work show for the first time a different inhibitory mechanism of action for Al3+ that involves intermediates of the ATP hydrolysis by these two Ca2+-transport ATPases. With grants of ANPCYT, CONICET, UBACYT y NIH