CONICET | Buscador de Institutos y Recursos Humanos

Alumminium inhibits the plasma membrane and the sarcoplasmic reticulum calcium pumps by different mechanisms De Sautu M, Ferreira-Gomes M, Takara Delia, Rossi JP and Mangialavori IC IQUIFIB-Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, UBA 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 action of Al3+ toxicity are linked to changes in the cellular calcium homeostasis, placing the transporting calcium pumps as potential targets. 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). These P-ATPases transports actively Ca2+ from the cytoplasm towards the extracellular medium and to the sarcoplasmic reticulum, respectively. For this purpose, we performed enzymatic measurements of the effect of Al3+ on purified preparations of PMCA and SERCA. Our results show that: (1) Al3+ inhibits Ca2+-ATPase activity of both enzymes with similar apparent affinity; (2) in the presence of Al3+, the apparent affinity for Ca2+ of SERCA decreased, leaving unmodified its affinity for PMCA; (3) Al3+ increase the apparent affinity for Mg2+ of both pumps, (4) Al3+ increases the phosphorylated intermediate (EP) of PMCA while it has not effect on SERCA; (5) ATP does not change the apparent inhibitory affinity for Al3+; (6) pH does not modify significantly the apparent inhibitory affinity for Al3+ for both PMCA and SERCA. This work show for the first time a different inhibitory mechanism of action for Al3+ that involves intermediates of the ATP hydrolysis by these two Ca2+-transport ATPases. With grants of ANPCYT, CONICET, UBACYT y NIH