Inhibition mechanisms of aluminium are different on the plasma membrane and the sarcoplásmic re-ticulum calcium pumps

DE SAUTU M, FERREIRA-GOMES, M., ROSSI, JPFC. ROSSI RC AND MANGIALAVORI, IC

Salto

Congreso; Latin American crosstalk in Biophisycs and physiology; 2015

Sociedades de Biofísica

Inhibition mechanisms of aluminium are different on the plasma membraneand the sarcoplasmic reticulum calcium pumps                                                                                                                                     De Sautu, M., Ferreira-Gomes, M., Rossi, JPFC. RossiRC and Mangialavori, IC.                                                               IQUIFIB- Dr. Paladini -Departamentode Química Biológica, Universidad de Buenos Aires Aluminium (Al3+) is involved with the pathophysiologyof neurodegenerative disorders, such as Parkinsonism dementia and Alzheimer?sdisease. The action of Al3+ toxicity is linked to changes in the cellularcalcium homeostasis, placing the transporting calcium pumps as potentialtargets. However, it has not been demonstrate that aluminium inhibits anytransmembrane transporter of mono and divalent metals. The aim of this work was to study the molecular inhibitorymechanism of Al3+ on Ca2+-ATPases like the plasmamembrane (PMCA) and the sarcoplasmic reticulum (SERCA). These P-ATPasestransport actively Ca2+. For this purpose, we performed enzymaticmeasurements of the effect of Al3+ on purified preparations of PMCAand SERCA. Our results show that: (1) Al3+  inhibits Ca2+-ATPase activityof both enzymes with similar apparent affinity; (2) in the presence of Al3+,the apparent affinity for Ca2+ of SERCA decreased, but not for PMCA;(3) Al3+ decreased the apparent affinity for Mg2+ of PMCA;(4) Al3+ increases the phosphorylated intermediate (EP) of PMCA while it has not effect onSERCA; (5) pH does not modify significantly the apparent inhibitory affinityfor Al3+ for both PMCA and SERCA. This work show for the first timea different inhibitory mechanism of action for Al3+ that involvesintermediates of the ATP hydrolysis by these two Ca2+-transport ATPases.