title: Overexpression of BAG3 Attenuates Hypoxia-Induced Cardiomyocyte Apoptosis by Inducing Autophagy.
abstract: BACKGROUND
  Hypoxia is a well-known factor in the promotion of apoptosis, which contributes to the development of numerous cardiac diseases, such as heart failure and myocardial infarction. Inhibiting apoptosis is an important therapeutic strategy for the treatment of related heart diseases caused by ischemia/hypoxic injury. Previous studies have demonstrated that BAG3 plays an important role in cardiomyocyte apoptosis and survival. However, the role of BAG3 in hypoxia-induced cardiomyocyte apoptosis remains to be clarified. Here, we demonstrate that BAG3 is induced by hypoxia stimuli in cultured cardiomyocytes.
  
  
  METHODS
  BAG3 expression level was measured in H9c2 cells treated with hypoxia for 48 h. Cell proliferation and apoptosis were tested using MTT assay and Annexin V FITC-PI staining assay, respectively. The mRNA or protein expression level of BAG3, LC3-I, LC3-II, Atg5, NF-x03BA;B p65 and phosphorylated NF-x03BA;B p65 were assessed by qRT-PCR and western blot assay, respectively. Resluts: Overexpression of BAG3 inhibited cell apoptosis and promoted proliferation in hypoxia-injured H9c2 cells. Furthermore, autophagy and NF-x03BA;B were activated by BAG3 overexpression, and the NF-x03BA;B inhibitor PDTC could inhibit the activation of autophagy induced by BAG3 overexpression. In addition, the autophagy inhibitor 3-MA partly impeded the inhibitory effect of BAG3 on hypoxia-induced cardiomyocyte apoptosis.
  
  
  CONCLUSIONS
  these results suggested that overexpression of BAG3 promoted cell proliferation and inhibited apoptosis by activating autophagy though the NF-x03BA;B signaling pathway in hypoxia-injured cardiomyocytes.
authors.affiliation: Department of Human Anatomy, Institute of Stem Cell and Regenerative Medicine, Dongguan Campus, Guangdong Medical University, Dongguan, China.
authors.forename: Jiankai
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhangyou
authors.initials: Z
authors.lastname: He
authors.forename: Wenjian
authors.initials: W
authors.lastname: Xiao
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Na
authors.forename: Tianxiu
authors.initials: T
authors.lastname: Wu
authors.forename: Kaixin
authors.initials: K
authors.lastname: Su
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Cui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D015870:Gene Expression; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D011392:Proline; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C545865:Atg5 protein, rat; C498807:BAG3 protein, rat; C526109:Anxa3 protein, rat; C066229:prolinedithiocarbamate