Different mechanisms of inhibition by aluminium on calcium pumps

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

Mar del Plata

Congreso; 238. LI Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas; 2015

Sociedad Argentina de Investigaciones Bioquímicas

Different mechanisms of inhibition by aluminium on calcium pumps DeSautu, M., Ferreira-Gomes, M., Rossi, JPFC. Rossi RC. and Mangialavori, IC.Institutode Química y Fisicoquímica Biológicas Dr. Prof. Alejandro Paladini (UBA-CONICET)irenem@qb.ffyb.uba.ar  Aluminium is involved with the pathophysiology ofneurodegenerative disorders, such as Parkinsonism dementia and Alzheimer?sdisease. The action of aluminum 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 aluminium on Ca-ATPases like the plasma membrane (PMCA)and the sarcoplasmic reticulum (SERCA). For this purpose, we performed enzymaticmeasurements of the effect of aluminium on different preparations of PMCA andSERCA. Our results show that aluminium: (1) inhibits Ca-ATPase activity of bothenzymes with similar apparent affinity; (2) decreases the apparent affinity forcalcium of SERCA, but not for PMCA; (3) decreases the apparent affinity for magnesiumof PMCA; (4) increases the phosphorylated intermediate (EP) of PMCA while it has not effect on SERCA; (5) pH does notmodify significantly the apparent inhibitory affinity for aluminium for both PMCAand SERCA. This work shows for the first time that aluminium inhibits thiscalcium transporter by different mechanism.  With grants of ANPCYT, CONICET yUBACYT