title: Acetylated FoxO1 mediates high-glucose induced autophagy in H9c2 cardiomyoblasts: regulation by a polyphenol -(-)-epigallocatechin-3-gallate.
abstract: OBJECTIVE
  FoxO1 acts as a pivotal transcription factor in insulin signaling. However, in hyperglycemia induced cardiac complications, whether FoxO1 is involved remains unclear. The goal of this study was to delineate the potential role of FoxO1 under high-glucose condition.
  
  
  METHODS
  We investigated insulin resistance and reactive oxygen species (ROS) generation in H9c2 cardiomyoblasts after high-glucose exposure. A series of autophagy biomarkers were measured and further confirmed by LC3 turnover assay. Using gene silencing and overexpression experiments we dissected the molecular mechanisms of FoxO1 regulated autophagy. We also tested the protective effect of (-)-epigallocatechin-3-gallate (EGCG, a green tea-derived polyphenol) in high-glucose treated H9c2 cardiomyoblasts.
  
  
  RESULTS
  High-glucose elicited elevated ROS, autophagy and FoxO1 abundance in cultured H9c2 cardiomyoblasts. Specifically, high-glucose significantly augmented the acetylated FoxO1 in cytosol. In line, compared with 3A-FoxO1 (majorly localized in nuclei with a strong transcriptional activity), overexpression of WT-FoxO1 led to more intense elevated autophagy with enhanced acetylation of FoxO1. In addition, FoxO1 RNAi brought down autophagy induced by high-glucose. Intriguingly, EGCG successfully reversed ROS, autophagy and acetylated FoxO1 in high-glucose treated H9c2 cells.
  
  
  CONCLUSIONS
  Our findings suggest that FoxO1, especially the acetylated form, regulates high-glucose induced autophagy in H9c2 cardiomyoblasts, which can be prevented by EGCG via a possible ROS-FoxO1 pathway.
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors: Jia
authors: J
authors: Liu
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors: Ying
authors: Y
authors: Tang
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors: Zhihui
authors: Z
authors: Feng
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors: Chen
authors: C
authors: Hou
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors: Hui
authors: H
authors: Wang
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors: Jiong
authors: J
authors: Yan
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors: Jing
authors: J
authors: Liu
authors: Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China.
authors: Weili
authors: W
authors: Shen
authors: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors: Weijin
authors: W
authors: Zang
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: j.liu@mail.xjtu.edu.cn.
authors: Jiankang
authors: J
authors: Liu
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: jglong@mail.xjtu.edu.cn.
authors: Jiangang
authors: J
authors: Long
mesh_terms: D000107:Acetylation / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D059808:Polyphenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002392:Catechin; D051858:Forkhead Transcription Factors; D005947:Glucose; D009419:Nerve Tissue Proteins; D059808:Polyphenols; D017382:Reactive Oxygen Species; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C045651:epigallocatechin gallate
keywords: Autophagy; Cardiomyoblasts; EGCG; FoxO1; High-glucose