The effects of aluminum on the plasma membrane calcium pump depends on the biophysics of reconstitution

DE SAUTU, MARILINA; MARIELA FERREIRA-GOMES; NICOLAS ANDRÉS SAFFIOTI; ROLANDO ROSSI; JUAN PABLO ROSSI; IRENE MANGIALAVORI

Congreso; XLVII Reunión Annual de la Sociedad de Biofísica Argentina.; 2018

Aluminium (Al3+) is involved with the pathophysiology of neurodegenerative disorders, such as Parkinsonism dementia and Alzheimer?s disease. The mechanisms that have been proposed to explain the toxicity of Al3+ are linked to changes in the cellular calcium homeostasis1. PMCA is a P-ATPase involved in the regulation of the calcium homeostasis. Its function is to transport Ca2+ from cytoplasm towards the extracellular medium against the electrochemical gradient modulating the cytoplasmic Ca2+ concentration. In previous works, we already showed that Al3+ irreversibly inhibits Ca2+-ATPase activity of PMCA by preventing thedephosphorylation of the pump2 and that AlCl3 inhibits calcium efflux mediated by PMCA in HEK293T cells3. Moreover, Pignataro et al4 showed that Ca2+-ATPase activity largely depends on the detergent/phosphatidylcholine reconstitution media and that the transition from mixed micelles to bicelles decreased the enzyme turnover.The aim of this work is to study if the effect of Al3+ on the protein is affected by the enzyme lipidicenvironment, since this would provide information of the distinctive effect that Al3+ would have depends onthe lipidic composition of the cell membrane where the PMCA is located.