H2S regulates endothelial nitric oxide synthase protein stability by promoting microRNA-455-3p expression

被引：33

作者：

Li, Xing-Hui ^{[1
]}

Xue, Wen-Long ^{[1
]}

Wang, Ming-Jie ^{[1
]}

Zhou, Yu ^{[1
]}

Zhang, Cai-Cai ^{[1
,2
]}

Sun, Chen ^{[1
]}

Zhu, Lei ^{[3
]}

Liang, Kun ^{[3
]}

Chen, Ying ^{[1
]}

Tao, Bei-Bei ^{[1
]}

Tan, Bo ^{[4
]}

Yu, Bo ^{[3
]}

Zhu, Yi-Chun ^{[1
]}

机构：

[1] Fudan Univ, Shanghai Med Coll, Shanghai Key Lab Bioact Small Mol, Res Ctr Aging & Med,Dept Physiol & Pathophysiol, Shanghai, Peoples R China

[2] Hainan Med Coll, Dept Physiol, Haikou 571101, Hainan, Peoples R China

[3] Fudan Univ, Huashan Hosp, Dept Vasc Surg, Shanghai 200040, Peoples R China

[4] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Clin Pharmacol, Shanghai, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金;

关键词：

CYSTATHIONINE GAMMA-LYASE; HYDROGEN-SULFIDE; ENDOGENOUS PRODUCTION; ANGIOGENESIS; PATHOGENESIS;

D O I：

10.1038/srep44807

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The aims of the present study are to determine whether hydrogen sulfide (H2S) is involved in the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production, and to identify the role of microRNA-455-3p (miR-455-3p) during those processes. In cultured human umbilical vein endothelial cells (HUVECs), the expression of miR-455-3p, eNOS protein and the NO production was detected after administration with 50 mu M NaHS. The results indicated that H2S could augment the expression of miR-455-3p and eNOS protein, leading to the increase of NO level. We also found that overexpression of miR-455-3p in HUVECs increased the protein levels of eNOS whereas inhibition of miR-455-3p decreased it. Moreover, H2S and miR-455-3p could no longer increase the protein level of eNOS in the presence of proteasome inhibitor, MG-132. In vivo, miR-455-3p and eNOS expression were considerably increased in C57BL/6 mouse aorta, muscle and heart after administration with 50 mu mol/ kg/day NaHS for 7 days. We also identified that H2S levels and miR-455-3p expression increased in human atherosclerosis plaque while H2S levels decreased in plasma of atherosclerosis patients. Our data suggest that the stability of eNOS protein and the NO production could be regulated by H2S through miR-455-3p.

引用

页数：12

共 36 条

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