Aluminum Inhibits the Plasma Membrane and Sarcoplasmic Reticulum Ca2+-ATPases by Different Mechanisms

MARILINA DE SAUTU; NICOLAS ANDRÉS SAFFIOTI; MARIELA FERREIRA-GOMES; ROLANDO ROSSI; JUAN PABLO F.C. ROSSI; IRENE CECILIA MANGIALAVORI

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018

0005-2736

Aluminum (Al3+) is involved in the pathophys-iology of neurodegenerative disorders. The mechanisms that have been proposed to ex-plain the action of Al3+ toxicity are linked to changes in the cellular calcium homeostasis, placing the transporting calcium pumps as potential targets. The aim of this work was to study the molecular inhibitory mechanism of Al3+ on Ca2+-ATPases such as the plasma membrane and the sarcoplasmic reticulum calcium pumps (PMCA and SERCA, respectively). These P-ATPases transport Ca2+ actively from the cy-toplasm towards the extracellular medium and to the sarcoplasmic reticulum, respectively. For this purpose, we performed enzymatic measurements of the effect of Al3+ on purified preparations of PMCA and SERCA. Our results show that Al3+ is an irre-versible inhibitor of PMCA and a slowly-reversible inhibitor of SERCA. The binding of Al3+ is affected by Ca2+ in SERCA, though not in PMCA. Al3+ prevents the phosphorylation of SERCA and, conversely, the dephosphory-lation of PMCA. The dephosphorylation time courses of the complex formed by PMCA and Al3+ (EPAl) in the presence of ADP or ATP show that EPAl is composed mainly by the conformer E2P. This work shows for the first time a dis-tinct mechanism of Al3+ inhibition that in-volves different intermediates of the reaction cycle of these two Ca2+-ATPases.