Protective effect of the flavonoid quercetin on the inhibition of plasma membrane calcium pump by aluminum

ANA RIESCO; MARILINA DE SAUTU; JUAN PABLO ROSSI; MARIELA FERREIRA-GOMES; IRENE MANGIALAVORI

Congreso; XLVII Reunión Annual de la Sociedad de Biofísica Argentina.; 2018

Aluminum is etiologically and epidemiologically related to several neurological disorders, including Alzheimer´s, Parkinson´s and amyotrophic lateral sclerosis. Exposure to high levels of this metal leads to neurofibrillary and neuronal degeneration and induces neurobehavioral deficits and morphological changes in the brain. The mechanism of aluminum neurotoxicity has been associated with several cellular phenomena, among them, a disturbance of intracellular Ca2+ homeostasis. Effectively, we have recently demonstrate that Al3+ inhibits the Ca2+-ATPase activity of the plasma membrane (PMCA) and sarcoplasmic reticulum (SERCA) calcium pumps [1] and produces an increase in intracellular Ca2+ [2]. Flavonoids are commonly found in fruits and vegetables and they are also part of human diet It is known that flavonoids have anti-oxidant activity. They prevent metal-mediated generation of free radicals because they are capable of sequestering metal ions by chelating In this context, the aim of this work was to evaluate if the flavonoid quercetin protects PMCA from inhibition by aluminum and to characterize the mechanism by which it does so. Our results suggest that quercetin protects PMCA from aluminum inhibition because it has a chelating effect on this trivalent cation and the quercetin-Al3+ complex does not bind to PMCA. In addition, the presence of quercetin partially reverses the effect of the inhibitory effect of aluminum, suggesting that its administration is a potential strategy to reverse the effect of aluminum at the cellular level.[1] De Sautu M, Saffioti NA, Ferreira-Gomes MS, Rossi RC, Rossi JPFC and Mangialavori IC. BBA-Biomembrane (2018) 860(8):1580-1588.[2] XLII Congreso da Sociedade Brasileira de Biofisica. Sao Pablo, Brasil. 27-29 de octubre de 2017. ?Inhibition of the plasma membrane calcium pump by aluminium in vitro and in living cells? De Sautu, M., Ferreira-Gomes M, Saffioti N, Rinaldi D, Rossi, R, Rossi JPFC and Mangialavori, IC. This work was supported by ANCYT PICT 2014 0065, CONICET PIP 0250 and Universidad de Buenos Aires 2014-2017: 20020130100254B