GSTpi Regulates VE-cadherin Stabilization Through Promoting S-glutathionylation of Src

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2020 Jan 14

PMID 31927409

Citations 12

Authors

Yang Yang

Xiaoliang Dong

Shuangning Zheng

Jinbing Sun

Juan Ye

Jiao Chen

Yuan Fang

Bing Zhao

Zhimin Yin

Peng Cao

Lan Luo

Affiliations

Soon will be listed here.

Abstract

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.

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