title: Ambra1 modulates starvation-induced autophagy through AMPK signaling pathway in cardiomyocytes.
abstract: Recent research has revealed a role for Ambra1, an autophagy-related gene-related (ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells and cancer cells. However, whether Ambra1 plays an important role in the autophagy pathway in cardiomyocytes is unknown. In this study, we hypothesized that Ambra1 is an important regulator of autophagy and apoptosis in cardiomyocytes. To test this hypothesis, we confirmed autophagic activity in serum-starved cardiomyocytes by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) localization, the presence of autophagosomes and LC3 protein levels. Cell apoptosis and viability were measured by annexin-V and PI staining and MTT assays. We determined that serum deprivation-induced autophagy was associated with Ambra1 upregulation in cardiomyocytes. When Ambra1 expression was reduced by siRNA, the cardiomyocytes were more sensitive to staurosporine-induced apoptosis. In addition, co-immunoprecipitation of Ambra1 and Beclin1 demonstrated that Ambra1 and Beclin1 interact in serum-starved or rapamycin-treated cardiomyocytes, suggesting that Ambra1 regulates autophagy in cardiomyocytes by interacting with Beclin1. Finally, we determined that starvation stress-induced activation of Ambra1 contributes to the attenuation of adaptive AMP-activated protein kinase (AMPK) signaling. In conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis through AMPK signaling pathway in cardiomyocytes that maintains the balance between autophagy and apoptosis.
authors.affiliation: Baotou Fourth Hospital, Inner Mongolia Autonomous Region, China.
authors.forename: Conghong
authors.initials: C
authors.lastname: Shi
authors.affiliation: The Image Section of Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Autonomous Region, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Baotou Fourth Hospital, Inner Mongolia Autonomous Region, China.
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.affiliation: Baotou Fourth Hospital, Inner Mongolia Autonomous Region, China.
authors.forename: Baohong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Baotou Fourth Hospital, Inner Mongolia Autonomous Region, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Teaching and Research Section of Human Anatomy and Histology, Inner Mongolia Medical University, Inner Mongolia Autonomous Region, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Beijing Anzhen Hospital of the Capital University of Medical Sciences, Beijing, China. Electronic address: ypchiaz@163.com.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Chi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D000071186:Beclin-1; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013312:Stress, Physiological
chemical_list: D055372:AMP-Activated Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D003470:Culture Media; D049452:Green Fluorescent Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D020123:Sirolimus; C000595495:Ambra1 protein, rat; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C568305:Prkaa1 protein, rat
keywords: Ambra1; Autophagy; Cardiomyocytes