Estrogen sulfotransferase (SULT1E1) regulates inflammatory response and lipid metabolism of human endothelial cells via PPARγ.

Yali Xu, Xiaoming Yang, Zhengyang Wang, Mengmeng Li, Yanxia Ning, Sifeng Chen, Lianhua Yin, Xiaobo Li

Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, China.

Molecular and cellular endocrinology 2013 Apr 30

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Estrogen sulfotransferase (SULT1E1) is a phase II drug-metabolizing enzyme known to catalyze sulfoconjugation of estrogens. 17β-estradiol (E2) plays a pivotal role in attenuating endothelial dysfunction. E2 can be further sulfated to estradiol sulfate (E2S) using SULT1E1. To date, there are no reports of expression and function of SULT1E1 in the endothelium. We identified that SULT1E1 is highly expressed in human umbilical vein endothelial cells (HUVECs) using immunofluorescence microscopy and Western immunoblot analyses. A synthesized siRNA targeting SULT1E1 was used to successfully suppress SULT1E1 expression and inhibit estrogen sulfation in HUVECs. This led to functional depletion, as confirmed by a SULT1E1 enzyme activity assay in vitro and by an in vivo estrogen sulfation assay. Knock-down of SULT1E1 in HUVECs resulted in regulation of genes involved in inflammation and lipid metabolism. Interestingly, this regulation was attenuated by PPARγ siRNA and by exposure to the PPARγ antagonist GW9662. Compared with cell response in the absence of estrogen, the effects of SULT1E1 interference on the inflammatory response and lipid metabolism related genes in the presence of 80nM estrogen were completely opposite. When exogenous estrogen was applied, cell responses depended on the ratio of E2 to E2S, due to the activity of SULT1E1, and the different regulation of these processes. It is suggested that E2 sulfation catalyzed by SULT1E1 plays an important role in modulating endothelial cell function. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Citation

Yali Xu, Xiaoming Yang, Zhengyang Wang, Mengmeng Li, Yanxia Ning, Sifeng Chen, Lianhua Yin, Xiaobo Li. Estrogen sulfotransferase (SULT1E1) regulates inflammatory response and lipid metabolism of human endothelial cells via PPARγ. Molecular and cellular endocrinology. 2013 Apr 30;369(1-2):140-9