Jiang, Q, Gao, Y, Wang, C et al. (11 more authors) (2017) Nitration of TRPM2 as a Molecular Switch Induces Autophagy during Brain Pericyte Injury. Antioxid Redox Signal, 27 (16). pp. 1297-1316. ISSN 1523-0864
Abstract
Aims: Dysfunction of neurovascular pericytes underlies breakdown of the blood-brain barrier, but the molecular mechanisms are largely unknown. In this study, we evaluated the role of the transient receptor potential melastatin-related 2 (TRPM2) channel and autophagy during brain pericyte injury both in vitro and in vivo. Results: A rapid induction in autophagy in human brain vascular pericytes, in the zinc oxide nanoparticles (ZnO-NP)-induced cell stress model, was paralleled with an increase in the expression of the TRPM2-S truncated isoform, which was abolished by treatment with a nitric oxide synthase inhibitor and a peroxynitrite scavenger. Furthermore, Y1485 in the C-terminus of the TRPM2 protein was identified as the tyrosine nitration substrate by mass spectrometry. Overexpression of the Y1485S TRPM2 mutant reduced LC3-II accumulation and pericyte injury induced by ZnO-NP. Consistently, LC3-II accumulation was reduced and pericytes were better preserved in intact brain microvessels of the TRPM2 knockout mice after ZnO-NP-induced vascular injury. Innovation and Conclusions: Our present study has revealed a novel mechanism of autophagy disturbance secondary to nitrosative stress-induced tyrosine nitration of TRPM2 during pericyte injury.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, Mary Ann Liebert, Inc. This is an author produced version of a paper published in Antioxidants and Redox Signaling. Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/ars.2016.6873. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Mar 2017 12:48 |
Last Modified: | 14 Mar 2018 01:38 |
Published Version: | https://doi.org/10.1089/ars.2016.6873 |
Status: | Published |
Publisher: | Mary Ann Liebert |
Identification Number: | 10.1089/ars.2016.6873 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113809 |