“Mechanism of aluminum inhibition of the plasma membrane and the sarcoplasmatic reticulum calcium pump”

THOMAS LAURA, FERREIRA-GOMES MARIELA, TAKARA DELIA, ROSSI JUAN PABLO F.C. AND MANGIALAVORI IRENE C

Tucumán

Congreso; XLI Reunión Anual de la Sociedad Argentina de Biofísica (SAB).; 2012

Sociedad Argentina de Biofísica

“Mechanism of aluminum inhibition of the plasma membrane and the sarcoplasmático reticulum calcium pump”. Thomas Laura, Ferreira-Gomes Mariela, Takara Delia, Rossi Juan Pablo F.C. and Mangialavori Irene C. Libro de Resúmenes: Pag 220 Among the group of metals with proven human toxicity, Aluminium (Al3+) is known to be highly neurotoxic. The systemic absorption of Al3+ is low, but select human subpopulations (infants, individuals with altered renal function) are more susceptible to Al3+ neurotoxicity. Although still controversial, Al3+ is proposed to be involved in the pathophysiology of neurodegenerative disorders, such as Parkinsonism dementia and Alzheimer’s disease1. The mechanisms that have been proposed to explain the action of Al3+ toxicity, are linked to changes in cellular calcium homeostasis, placing like potentials target to transporting calcium proteins2. The aim of this work was to study the effect of Al3+ on Ca2+-ATPases of plasma membrane (PMCA) and of sarcoplasmic reticulum (SERCA). These P-ATPases transports actively Ca2+- from the cytoplasm towards the extracellular medium and to the sarcoplasmic reticulum, respectively. It reaction cycle is described by an E1-E2 model and involve phosphorylate intermediaries (EP) from the ATP hydrolysis. For this purpose, we performed kinetic 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; (2) in the presence of Al3+, PMCA apparent affinity for Ca2+ increases whereas in SERCA decreases; (3) Al3+ increases the apparent affinity for Mg2 of PMCA, and, (4) Al3+, in the presence of Ca2+ increases the phosphorylate intermediary (EP) of PMCA while it has not effect on SERCA. In this work we showed for the first time a different molecular mechanism of toxicity for Al3+ that involves intermediaries of the reaction of ATP hydrolysis for both Ca2+-ATPases. 1Sandra V. Verstraeten and Lucila Aimo (2008) Arch Toxicol 82:789–802 2David L. Jones, Leon V. Kochian, and Simon Gilroy (1996) Plant Physiol. 11 2: 21 7-227