Different mechanisms of inhibition by aluminium on calcium pumps

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

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas (SAIB).; 2015

Aluminium is involved with the pathophysiology of neurodegenerative disorders, such as Parkinsonism dementia and Alzheimer?s disease. The action of aluminum 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 aluminium on Ca-ATPases like the plasma membrane (PMCA) and the sarcoplasmic reticulum (SERCA). For this purpose, we performed enzymatic measurements of the effect of aluminium on different preparations of PMCA and SERCA. Our results show that aluminium: (1) inhibits Ca-ATPase activity of both enzymes with similar apparent affinity; (2) decreases the apparent affinity for calcium of SERCA, but not for PMCA; (3) decreases the apparent affinity for magnesium of PMCA; (4) 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 aluminium for both PMCA and SERCA. This work shows for the first time that aluminium inhibits this calcium transporter by different mechanism. With grants of ANPCYT, CONICET y UBACYT