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

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

La Plata

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Sociedad Argentina de Biofísica

Aluminium (Al3+) is involved with the pathophysiology of neurodegenerativedisorders, such as Parkinsonism dementia and Alzheimer?s disease. Themechanisms that have been proposed to explain the toxicity of Al3+ are linked tochanges in the cellular calcium homeostasis. PMCA is a P-ATPase involved in theregulation of the calcium homeostasis. Its function is to transport Ca2+ fromcytoplasm towards the extracellular medium against the electrochemical gradientmodulating the cytoplasmic Ca2+ concentration. In previous works, we alreadyshowed that Al3+ irreversibly inhibits Ca2+-ATPase activity of PMCA by preventingthe dephosphorylation of the pump and that AlCl3 inhibits calcium efflux mediatedby PMCA in HEK293T cells.The aim of this work was to study if the effect of Al3+ on the protein is affected bythe enzyme lipidic environment, since this would provide information of thedistinctive effect that Al3+ would have depends on the lipidic composition of thecell membrane where the PMCA is located. To characterize this effect, wereconstituted the enzyme in different lipidic environment and evaluated itsinhibition by Al3+. In addition, to characterize if the differences observed were dueto an effect of the lipidic environment on the enzyme structure or an Al3+ chelatingeffect, we measure the interaction of Al3+ with different lipidic structures.In the isolated system, increasing concentration of acidic phospholipids decreasedthe Al3+ effect on PMCA. However, when PMCA is reconstituted with brain extractlipids, Al3+ increased its Ca2+-ATPase activity. These results suggest that Al3+affects PMCA both by its binding to the enzyme and modifying the biophysicalcharacteristics of the pump lipid environment.