H2S regulates endothelial nitric oxide synthase protein stability by promoting microRNA-455-3p expression.
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 μM 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 μmol/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.
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Xing-Hui
XH
Li
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Wen-Long
WL
Xue
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Ming-Jie
MJ
Wang
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Yu
Y
Zhou
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of physiology, Hainan Medical College, Haikou, Hainan 571101, China.
Cai-Cai
CC
Zhang
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Chen
C
Sun
Department of Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Lei
L
Zhu
Department of Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Kun
K
Liang
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Ying
Y
Chen
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Bei-Bei
BB
Tao
Department of Clinical Pharmacology, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Bo
B
Tan
Department of Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Bo
B
Yu
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Yi-Chun
YC
Zhu
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D044842:Cullin Proteins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D034622:RNA Interference; D025801:Ubiquitin / Q000378:metabolism
C503645:CUL3 protein, human; D044842:Cullin Proteins; C583404:MIRN455 microRNA, human; D035683:MicroRNAs; D025801:Ubiquitin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D046988:Proteasome Endopeptidase Complex; D006862:Hydrogen Sulfide