Aluminum inhibits the plasma membrane and sarcoplasmic reticulum Ca2+-ATPases by different mechanisms

Aluminum inhibits the plasma membrane and sarcoplasmic reticulum Ca2+-ATPases by different... Aluminum (Al3+) is involved in the pathophysiology of neurodegenerative disorders. 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 such as the plasma membrane and the sarcoplasmic reticulum calcium pumps (PMCA and SERCA, respectively). These P-ATPases transport Ca2+ actively 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 Al3+ is an irreversible inhibitor of PMCA and a slowly-reversible inhibitor of SERCA. The binding of Al3+ is affected by Ca2+ in SERCA, though not in PMCA. Al3+ prevents the phosphorylation of SERCA and, conversely, the dephosphorylation of PMCA. The dephosphorylation time courses of the complex formed by PMCA and Al3+ (EPAl) in the presence of ADP or ATP show that EPAl is composed mainly by the conformer E2P.This work shows for the first time a distinct mechanism of Al3+ inhibition that involves different intermediates of the reaction cycle of these two Ca2+-ATPases. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biochimica et Biophysica Acta Biomembranes Or Bba Biomembranes Elsevier

Aluminum inhibits the plasma membrane and sarcoplasmic reticulum Ca2+-ATPases by different mechanisms

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier B.V.
ISSN
0005-2736
eISSN
1879-2642
D.O.I.
10.1016/j.bbamem.2018.05.014
Publisher site
See Article on Publisher Site

Abstract

Aluminum (Al3+) is involved in the pathophysiology of neurodegenerative disorders. 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 such as the plasma membrane and the sarcoplasmic reticulum calcium pumps (PMCA and SERCA, respectively). These P-ATPases transport Ca2+ actively 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 Al3+ is an irreversible inhibitor of PMCA and a slowly-reversible inhibitor of SERCA. The binding of Al3+ is affected by Ca2+ in SERCA, though not in PMCA. Al3+ prevents the phosphorylation of SERCA and, conversely, the dephosphorylation of PMCA. The dephosphorylation time courses of the complex formed by PMCA and Al3+ (EPAl) in the presence of ADP or ATP show that EPAl is composed mainly by the conformer E2P.This work shows for the first time a distinct mechanism of Al3+ inhibition that involves different intermediates of the reaction cycle of these two Ca2+-ATPases.

Journal

Biochimica et Biophysica Acta Biomembranes Or Bba BiomembranesElsevier

Published: Aug 1, 2018

References

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