Urotensin II Protects Cardiomyocytes from Apoptosis Induced by Oxidative Stress through the CSE/H2S Pathway

International Journal of Molecular Sciences

Hui Gong¹  Zhidan Chen¹  Xiaoyi Zhang¹  Yang Li¹  Jie Zhang³  Ying Chen²  Yingjiong Ding²  Guoping Zhang¹  Chunjie Yang¹  Yichun Zhu²  Yunzeng Zou³ 

[1] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; E-Mails:;Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China; E-Mails:;Department of Radiology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China

关键词: urotensin II;    apoptosis;    cardiomyocyte;    cystathionine-γ-lyase (CSE);    hydrogen sulfide (H₂S);   

DOI  :  10.3390/ijms160612482

来源: mdpi

【 摘 要 】

Plasma urotensin II (UII) has been observed to be raised in patients with acute myocardial infarction; suggesting a possible cardiac protective role for this peptide. However, the molecular mechanism is unclear. Here, we treated cultured cardiomyocytes with H₂O₂ to induce oxidative stress; observed the effect of UII on H₂O₂-induced apoptosis and explored potential mechanisms. UII pretreatment significantly reduced the number of apoptotic cardiomyocytes induced by H₂O₂; and it partly abolished the increase of pro-apoptotic protein Bax and the decrease of anti-apoptotic protein Bcl-2 in cardiomyocytes induced by H₂O₂. SiRNA targeted to the urotensin II receptor (UT) greatly inhibited these effects. Further analysis revealed that UII increased the production of hydrogen sulfide (H₂S) and the level of cystathionine-γ-lyase (CSE) by activating the ERK signaling in H₂O₂-treated-cardiomyocytes. Si-CSE or ERK inhibitor not only greatly inhibited the increase in CSE level or the phosphorylation of ERK induced by UII but also reversed anti-apoptosis of UII in H₂O₂-treated-cadiomyocytes. In conclusion, UII rapidly promoted the phosphorylation of ERK and upregulated CSE level and H₂S production, which in turn activated ERK signaling to protect cardiomyocytes from apoptosis under oxidative stress. These results suggest that increased plasma UII level may protect cardiomyocytes at the early-phase of acute myocardial infarction in patients.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.