Estrogen-dependent inhibition of dextrose-induced endoplasmic reticulum stress and superoxide generation in endothelial cells

Free Radical Biology & Medicine
Michael J HaasArshag D Mooradian

Abstract

Increased oxidative stress and endoplasmic reticulum stress (ER stress) have been implicated in atherosclerosis. Estrogens have potent antioxidant activity but their effects on ER stress have not been well studied. Therefore, we studied the effects of estradiol and related sex steroids on dextrose-induced ER stress and superoxide (SO) generation in human umbilical vein endothelial cells (HUVECs). Oxidative stress was measured using hydroethidine fluorescence and MCLA chemiluminescence. ER stress was measured with an ER stress-sensitive secreted alkaline phosphatase (ES-TRAP) assay and by Western blot analysis of the expression of GRP78, JNK1, and phosphorylated JNK1, markers for ER stress. A supraphysiological dextrose concentration (27.5mM) increased ER stress and SO generation compared to treatment with a physiological concentration (5.5mM) of dextrose. In the presence of estradiol or testosterone (T), ER stress and SO generation were significantly reduced. In contrast to T-treated cells, dihydrotestosterone and 5-methyltestosterone were ineffective at alleviating ER stress or SO generation. When HUVECs were treated with T and the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione, T was no longer effective at suppressing ...Continue Reading

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Citations

Mar 1, 2014·The Journal of Endocrinology·Rodrigo S FortunatoDenise P Carvalho
Jul 3, 2013·Physiology·Margaret A Zimmerman, Jennifer C Sullivan
Jul 16, 2014·Current Eye Research·Saradha Iragavarapu, Michael B Gorin
Jan 26, 2013·Trends in Molecular Medicine·Jie CuiRena Li
Mar 5, 2014·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Wei-Hong LiXiu-Hua Liu
Oct 23, 2016·Free Radical Biology & Medicine·Michael J HaasArshag D Mooradian
Oct 26, 2016·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Arshag D Mooradian
Feb 25, 2014·American Journal of Men's Health·Jeannie J SuT Mike Hsieh
Feb 10, 2018·Current Atherosclerosis Reports·Saamir A HassanSyed Wamique Yusuf
Nov 7, 2019·Journal of Cellular Biochemistry·Wen-Jing LiuSheng-Xiang Lin
Sep 24, 2020·Oxidative Medicine and Cellular Longevity·Shengjie YangSongzi Wang
May 16, 2021·The Journal of Surgical Research·Jian TongJia Meng

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