Autophagy is promoted as a response to such environmental stress conditions as ATP depletion and excessive accumulation of reactive oxygen species (ROS). Multiple signalling pathways, including AMP-activated protein kinase (AMPK), are indicated to promote autophagy in ischaemic/hypoxic (I/R) heart. However, it's far more to clarify the orchestrated cross-talk between AMPK and other signalling pathways in the autophagy. In the present study, we investigated the autophagy induction by hypoxia in Rat H9C2 cardiomyocytes with LC3-EGFP reporter, EM and Western blot analysis. Then, we examined the promotion of forkhead box O (FOXO) 3, one member of FOXO transcriptional protein family, by hypoxia in Rat H9C2 cells and determined the mediation of FOXO 3 in the hypoxia-induced autophagy in H9C2 cells. In addition, we investigated the role of AMPK signalling in the FOXO3-mediated, hypoxia-induced autophagy in H9C2 cells. It was demonstrated that hypoxia induced significant autophagy in H9C2 cells, via promoting autophagic vesicles, inducing the conversion of LC3-I to LC3-II and up-regulating autophagy-related (ATG) markers. Moreover, FOXO3 was up-regulated by the hypoxia in H9C2 cells; and the knockdown of FOXO3 significantly reduced the hypoxia-induced autophagy. In addition, AMPK signalling was significantly promoted by hypoxia in H9C2 cells, and the chemical manipulation of AMPK exerted significant influence on the hypoxia-induced autophagy and on the FOXO3 level. In conclusion, FOXO3 regulated the hypoxia-induced autophagy in cardiomyocytes, and AMPK mediated the FOXO3 promotion during the autophagy induction by hypoxia, implying the key regulatory role of FOXO3 and AMPK signalling in the hypoxia- induced autophagy in cardiomyocytes.
基金：
Beijing Anzhen Hospital, Capital Medical University [AZ2014015]
第一作者机构：[1]Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, Beijing 100029, Peoples R China;
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, Beijing 100029, Peoples R China;
推荐引用方式(GB/T 7714)：
Chi Yunpeng,Shi Conghong,Zhao Yang,et al.Forkhead box O (FOXO) 3 modulates hypoxia-induced autophagy through AMPK signalling pathway in cardiomyocytes[J].BIOSCIENCE REPORTS.2016,36(3):-.doi:10.1042/BSR20160091.
APA：
Chi, Yunpeng,Shi, Conghong,Zhao, Yang&Guo, Chengjun.(2016).Forkhead box O (FOXO) 3 modulates hypoxia-induced autophagy through AMPK signalling pathway in cardiomyocytes.BIOSCIENCE REPORTS,36,(3)
MLA：
Chi, Yunpeng,et al."Forkhead box O (FOXO) 3 modulates hypoxia-induced autophagy through AMPK signalling pathway in cardiomyocytes".BIOSCIENCE REPORTS 36..3(2016):-
