INVESTIGADORES
ROSSI juan pablo Francisco
congresos y reuniones científicas
Título:
Aluminum inhibits the plasma membrane and the sarcoplasmic reticulum calcium pumps by different mechanisms
Autor/es:
DE SAUTU, M., FERREIRA-GOMES, M., TAKARA, D., ROSSI, JPFC. AND MANGIALAVORI, IC.
Lugar:
Villa Carlos Paz, Córdoba
Reunión:
Congreso; ? XLII. Reunión Anual de la Sociedad Argentina de Biofísica (SAB).; 2013
Institución organizadora:
SAB
Resumen:
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