GSTpi regulates VE-cadherin stabilization through promoting S-glutathionylation of Src.

GSTpi is a Phase II metabolic enzyme which is originally considered as an important facilitator of cellular detoxification. Here, we found that GSTpi stabilized VE-cadherin in endothelial cell membrane through inhibiting VE-cadherin phosphorylation and VE-cadherin/catenin complex dissociation, and consequently maintained endothelial barrier function. Our findings demonstrated a novel mechanism that GSTpi inhibited VE-cadherin phosphorylation through suppressing the activation of Src/VE-cadherin pathway. Mass spectrometry analysis and molecular docking showed that GSTpi enhanced Src S-glutathionylation at Cys185, Cys245, and Cys400 of Src. More important, we found that GSTpi promoted S-glutathionylation of Src was essential for GSTpi to inhibit Src phosphorylation and activation. Furthermore, in vivo experiments indicated that AAV-GSTpi exerted the protective effect on pulmonary vessel permeability in the animal model of acute lung injury. This study revealed a novel regulatory effect of GSTpi on vascular endothelial barrier function and the importance of S-glutathionylation of Src induced by GSTpi in the activation of Src/VE-cadherin pathway. Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Yang Yang, Xiaoliang Dong, Shuangning Zheng, Jinbing Sun, Juan Ye, Jiao Chen, Yuan Fang, Bing Zhao, Zhimin Yin, Peng Cao, Lan Luo. GSTpi regulates VE-cadherin stabilization through promoting S-glutathionylation of Src. Redox biology. 2020 Feb;30:101416

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PMID: 31927409

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