Differences and similarities in the mechanisms of inhibition of aluminium on the plasma membrane and the sarcoplasmic reticulum calcium pumps.?

DE SAUTU, M.; SAFFIOTI, N; FERREIRA GOMES, M; RINALDI, D.E; ROSSI, R.C; ROSSI, J.P.; MANGIALAVORI, I. .

Tucuman

Congreso; III Latin American Federation of Biophysical Societies (LAFeBS). IX IberoAmerican Congress of Biophysics. XLV Reunion Annual SAB 2016.; 2016

LAFeBS- SAB

Aluminium (Al3+) is a metal widely distributed in the environment. Al3+ is involved with the pathophysiology of neurodegenerative disorders, such as Parkinsonism dementia and Alzheimer?s disease. Several mechanisms explain itsneurotoxicity, for example, damage to the glycolytic metabolism, lipid peroxidation1 leading increased free radicals,protein modifications and changes in the cellular calcium homeostasis2. However, there is no evidence at the molecular level on whether Ca2+-pumps are involved in the process of aluminum intoxication.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), two essential ATPases for the homeostasis of the cytoplasmic concentration of Ca2+. Here, we use as cell model the HEK293T cells and purified preparations of the calcium pumps to characterize the inhibitory mechanism of Al3+ at the molecular level. Our results showed that Al3+ inhibits Ca2+-ATPase activity of both enzymes with a similar apparent affinity, but withdifferent mechanisms. PMCA phosphorylated intermediate increases as a function of Al3+ concentration with a hyperbolic behavior while in SERCA it decreases. In SERCA, Ca2+ has a protective effect on the inhibition by AlCl3.