过氧亚硝酸盐
自噬
TRPM2型
周细胞
细胞生物学
一氧化氮
化学
生物化学
内皮干细胞
瞬时受体电位通道
生物
受体
体外
超氧化物
细胞凋亡
酶
有机化学
作者
Quan Jiang,Yinping Gao,Chengkun Wang,Rongrong Tao,Yan Wu,Kaiyu Zhan,Mei‐Hua Liao,Nannan Lu,Ying‐Mei Lu,Christopher S. Wilcox,Jianhong Luo,Lin‐Hua Jiang,Wei Yang,Feng Han
标识
DOI:10.1089/ars.2016.6873
摘要
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.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. Antioxid. Redox Signal. 27, 1297-1316.
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