GSTpi regulates VE-cadherin stabilization through promoting S-glutathionylation of Src
Identifieur interne : 000806 ( Main/Exploration ); précédent : 000805; suivant : 000807GSTpi regulates VE-cadherin stabilization through promoting S-glutathionylation of Src
Auteurs : Yang Yang [République populaire de Chine] ; Xiaoliang Dong [République populaire de Chine] ; Shuangning Zheng [République populaire de Chine] ; Jinbing Sun [République populaire de Chine] ; Juan Ye [République populaire de Chine] ; Jiao Chen [République populaire de Chine] ; Yuan Fang [République populaire de Chine] ; Bing Zhao [République populaire de Chine] ; Zhimin Yin [République populaire de Chine] ; Peng Cao [République populaire de Chine] ; Lan Luo [République populaire de Chine]Source :
- Redox Biology [ 2213-2317 ] ; 2019.
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,
Url:
DOI: 10.1016/j.redox.2019.101416
PubMed: 31927409
PubMed Central: 6957793
Affiliations:
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Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Yin, Zhimin" sort="Yin, Zhimin" uniqKey="Yin Z" first="Zhimin" last="Yin">Zhimin Yin</name><affiliation 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last="Yang">Yang Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Dong, Xiaoliang" sort="Dong, Xiaoliang" uniqKey="Dong X" first="Xiaoliang" last="Dong">Xiaoliang Dong</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Shuangning" sort="Zheng, Shuangning" uniqKey="Zheng S" first="Shuangning" last="Zheng">Shuangning Zheng</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Jinbing" sort="Sun, Jinbing" uniqKey="Sun J" first="Jinbing" last="Sun">Jinbing Sun</name><affiliation wicri:level="1"><nlm:aff id="aff6">Changshu No.1 People's Hospital Affiliated to Soochow University, Changshu, 215500, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Changshu No.1 People's Hospital Affiliated to Soochow University, Changshu, 215500</wicri:regionArea><wicri:noRegion>215500</wicri:noRegion></affiliation></author><author><name sortKey="Ye, Juan" sort="Ye, Juan" uniqKey="Ye J" first="Juan" last="Ye">Juan Ye</name><affiliation wicri:level="1"><nlm:aff id="aff2">Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Jiao" sort="Chen, Jiao" uniqKey="Chen J" first="Jiao" last="Chen">Jiao Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Bing" sort="Zhao, Bing" uniqKey="Zhao B" first="Bing" last="Zhao">Bing Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff2">Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Yin, Zhimin" sort="Yin, Zhimin" uniqKey="Yin Z" first="Zhimin" last="Yin">Zhimin Yin</name><affiliation wicri:level="1"><nlm:aff id="aff3">Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Cao, Peng" sort="Cao, Peng" uniqKey="Cao P" first="Peng" last="Cao">Peng Cao</name><affiliation wicri:level="1"><nlm:aff id="aff2">Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023</wicri:regionArea><wicri:noRegion>210023</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Lan" sort="Luo, Lan" uniqKey="Luo L" first="Lan" last="Luo">Lan Luo</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author></analytic><series><title level="j">Redox Biology</title><idno type="eISSN">2213-2317</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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, <italic>in vivo</italic> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Han, J" uniqKey="Han J">J. Han</name></author><author><name sortKey="Weisbrod, R M" uniqKey="Weisbrod R">R.M. Weisbrod</name></author><author><name sortKey="Shao, D" uniqKey="Shao D">D. Shao</name></author><author><name sortKey="Watanabe, Y" uniqKey="Watanabe Y">Y. Watanabe</name></author><author><name sortKey="Yin, X" uniqKey="Yin X">X. Yin</name></author><author><name sortKey="Bachschmid, M M" uniqKey="Bachschmid M">M.M. Bachschmid</name></author><author><name sortKey="Seta, F" uniqKey="Seta F">F. Seta</name></author><author><name sortKey="Janssen Heininger, Y M W" uniqKey="Janssen Heininger Y">Y.M.W. 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Bhatnagar</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name></noRegion><name sortKey="Cao, Peng" sort="Cao, Peng" uniqKey="Cao P" first="Peng" last="Cao">Peng Cao</name><name sortKey="Cao, Peng" sort="Cao, Peng" uniqKey="Cao P" first="Peng" last="Cao">Peng Cao</name><name sortKey="Cao, Peng" sort="Cao, Peng" uniqKey="Cao P" first="Peng" last="Cao">Peng Cao</name><name sortKey="Chen, Jiao" sort="Chen, Jiao" uniqKey="Chen J" first="Jiao" last="Chen">Jiao Chen</name><name sortKey="Chen, Jiao" sort="Chen, Jiao" uniqKey="Chen J" first="Jiao" last="Chen">Jiao Chen</name><name sortKey="Dong, Xiaoliang" sort="Dong, Xiaoliang" uniqKey="Dong X" first="Xiaoliang" last="Dong">Xiaoliang Dong</name><name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name><name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name><name sortKey="Luo, Lan" sort="Luo, Lan" uniqKey="Luo L" first="Lan" last="Luo">Lan Luo</name><name sortKey="Sun, Jinbing" sort="Sun, Jinbing" uniqKey="Sun J" first="Jinbing" last="Sun">Jinbing Sun</name><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name><name sortKey="Ye, Juan" sort="Ye, Juan" uniqKey="Ye J" first="Juan" last="Ye">Juan Ye</name><name sortKey="Ye, Juan" sort="Ye, Juan" uniqKey="Ye J" first="Juan" last="Ye">Juan Ye</name><name sortKey="Yin, Zhimin" sort="Yin, Zhimin" uniqKey="Yin Z" first="Zhimin" last="Yin">Zhimin Yin</name><name sortKey="Zhao, Bing" sort="Zhao, Bing" uniqKey="Zhao B" first="Bing" last="Zhao">Bing Zhao</name><name sortKey="Zhao, Bing" sort="Zhao, Bing" uniqKey="Zhao B" first="Bing" last="Zhao">Bing Zhao</name><name sortKey="Zheng, Shuangning" sort="Zheng, Shuangning" uniqKey="Zheng S" first="Shuangning" last="Zheng">Shuangning Zheng</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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