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

Abstract

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.

• Authors: Hui Gong, Zhidan Chen, Xiaoyi Zhang, Yang Li, Jie Zhang, Ying Chen, Yingjiong Ding, Guoping Zhang, Chunjie Yang, Yichun Zhu, Yunzeng Zou
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 16 Issue 6 Pg. 12482-98 (Jun 03 2015) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 26047336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bax protein, rat
• Proto-Oncogene Proteins c-bcl-2
• Urotensins
• bcl-2-Associated X Protein
• urotensin II
• Hydrogen Peroxide
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Animals
• Apoptosis (drug effects)
• Cells, Cultured
• Cystathionine gamma-Lyase (metabolism)
• Gene Expression Regulation (drug effects)
• Hydrogen Peroxide (pharmacology)
• Hydrogen Sulfide (metabolism)
• Male
• Myocytes, Cardiac (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Urotensins (pharmacology)
• bcl-2-Associated X Protein (metabolism)