FOXO1 silence aggravates oxidative stress-promoted apoptosis in cardiomyocytes by reducing autophagy.
Mechanisms underlining oxidative stress-induced injury to cardiomyocytes during myocardial infarction (MI) or acute ischemia/reperfusion (I/R) are not well recognized. Forkhead box O (FOXO) transcription factors have been defined as critical mediators of oxidative stress resistance in multiple cell types, but their cardioprotective functions have not been reported previously. In the present study, we investigated the promotion to FOXO1 by the treatment with hydrogen peroxide (H2O2) during the H2O2-induced apoptosis in cardiomyocyte H9c2 cells. We then silenced FOXO1 with FOXO1-specific siRNA, and re-evaluated the H2O2-induced apoptosis. In addition, we also examined the H2O2-induced autophagy and the autophagy induction post FOXO1 silence. Results demonstrated that H2O2 induced a significantly high level of apoptosis in H9c2 cells. Interestingly, the FOXO1 in both mRNA and protein levels were not significantly regulated, however, the phosphorylated form of FOXO1 was significantly promoted in the H2O2-treated H9c2 cells. On the other hand, post the significant knockout of FOXO1 with the transfection with FOXO1-specific siRNA, the apoptosis induction was more significant in H9c2 cells subjected to H2O2. In addition, we found a significantly higher level of autophagy induction in the H2O2-treated H9c2 cells. However, the autophagy was markedly reduced by the knockout of FOXO1. In summary, these data support the critical role for FOXO1 in promoting cardiomyocytes against oxidative stress probably through inducing autophagy.
Vasculocardiology Deparment, Zhujiang Hospital, Southern Medical University, China.
Yuzhen
Y
Ning
Zhiliang
Z
Li
Zhihong
Z
Qiu
D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D032383:Myocytes, Cardiac / Q000502:physiology*; D018384:Oxidative Stress; D010766:Phosphorylation; D034741:RNA, Small Interfering
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide