Abstract 265: Uroetensin II Protects Cardiomyocytes from Apoptosis Induced by Oxidative Stress through Cystathionine-γ-Lyase (CSE)/Hydrogen Sulfide Pathway
Plasma UII has been observed to be raised in patients with acute myocardial infarction, a lower UII response is associated with more severe injury of myocardium, suggesting a possible cardioprotective role for this peptide. In the present study, we studied plasma UII concentration of thirty patients admitted to the Cardiology Department with acute myocardial infartion.The results showed that plasma UII was sharply increased in patients compared to that in health control within one week after admission. We then explore whether UII could protect cardiomyocytes from injury induced by oxidative stress. Cultured cardiomyocyte were treated with H2O2 to induce oxidative stress, and the influence of UII on H2O2-induced apoptosis was observed. The results showed that UII pretreatment significantly reduced the number of TUNEL-positive cardiomyocytes induced by H2O2, and it partly abolished the upregulation of pro-apoptotic protein Bax and the down-regulation of anti-apoptotic protein Bcl-2. siRNA targeted to urotensin receptor (UT) greatly inhibited these effects. H2S has been reported to exert protective effect on cardiomyocytes, we detected the effect of UII on H2S production and CSE (Major H2S-producing enzyme) expressions in cardiomyocytes exposed to H2O2.The present data revealed that UII increased the H2S production by enhancing the expression of CSE by activating the ERK signaling in cardiomyocytes exposed to H2O2. Si-CSE or ERK inhibitor not only greatly inhibited the upregulation of CSE or the phosphorylation of ERK induced by UII but also reversed UII-induced-upregulation of H2S production and anti-apoptosis in cadiomyocytes exposed to H2O2.
In conclusion, UII rapidly promoted the phosphorylation of ERK, increased CSE exression and induced H2S production, which in turn enhanced the p-ERK level to protect cardiomyocytes from apoptosis under ischemic or oxidative stress. The increased plasma UII level in patients may be critical for cardiac protection in patients at early-phase of acute myocardial infarction.
Author Disclosures: H. Gong: None Z. Chen: None X. Zhang: None J. Zhang: None Y. Li: None Y. Ye: None G. Zhang: None C. Yang: None Y. Zou: None.
- © 2014 by American Heart Association, Inc.