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Endoplasmic reticulum stress and oxidative stress drive endothelial dysfunction induced by high selenium

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submitted on 2023-03-15, 08:03 and posted on 2023-03-16, 06:23 authored by Matshediso Zachariah, Hatem Maamoun, Larissa Milano, Margaret P. Rayman, Lisiane B. Meira, Abdelali Agouni

Selenium is an essential trace element important for human health. A balanced intake is, however, crucial to maximize the health benefits of selenium. At physiological concentrations, selenium mediates antioxidant, anti-inflammatory, and pro-survival actions. However, supra-nutritional selenium intake was associated with increased diabetes risk leading potentially to endothelial dysfunction, the initiating step in atherosclerosis. High selenium causes apoptosis in cancer cells via endoplasmic reticulum (ER) stress, a mechanism also implicated in endothelial dysfunction. Nonetheless, whether ER stress drives selenium-induced endothelial dysfunction, remains unknown. Here, we investigated the effects of increasing concentrations of selenium on endothelial cells. High selenite reduced nitric oxide bioavailability and impaired angiogenesis. High selenite also induced ER stress, increased reactive oxygen species (ROS) production, and apoptosis. Pretreatment with the chemical chaperone, 4-phenylbutyrate, prevented the toxic effects of selenium. Our findings support a model where high selenite leads to endothelial dysfunction through activation of ER stress and increased ROS production. These results highlight the importance of tailoring selenium supplementation to achieve maximal health benefits and suggest that prophylactic use of selenium supplements as antioxidants may entail risk.

Other Information

Published in: Journal of Cellular Physiology
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: http://dx.doi.org/10.1002/jcp.30175

History

Language

  • English

Publisher

Wiley

Publication Year

  • 2020

Institution affiliated with

  • Qatar University

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