title: Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes.
abstract: OBJECTIVE
  To investigate the effect of advanced glycation endproduct-induced autophagy in rat cardiomyocytes and to identify the role of autophagy in advanced glycation end product-induced cell apoptosis.
  
  
  METHODS
  After cultured rat cardiomyocytes were treated with advanced glycation end products (AGEs), protein expression was detected by western blotting, autophagosomes were observed by electron microscopy, the cell apoptotic rate was determined by flow cytometry, and cell variability was quantified by the MTT assay.
  
  
  RESULTS
  After cultured cardiomyocytes were treated with AGEs, the level of autophagy-associated protein LC3-II was up-regulated and SQSTM1/p62 was down-regulated; the number of autophagosomes was increased. Compared with the control group, the apoptotic rate of cardiomyocytes increased, and the cardiomyocyte viability was decreased in the AGE-treated group. Furthermore, pretreating cells with3-MA, an autophagy inhibitor, could enhance these effects. Treatment with AGEs activated phospho-ERK, phospho-JNK, and phospho-p38/MAPK but inhibited phospho-Akt and phospho-mTOR. Pretreatment with an ERK inhibitor and an Akt activator could inhibit AGE-induced autophagy, demonstrating that AGEs induce autophagy in cardiomyocytes through the ERK and Akt signalling pathways.
  
  
  CONCLUSIONS
  AGEs can induce autophagy through the PI3K/AKT/mTOR and ERK signalling pathways and induce apoptosis through the PI3K/AKT/mTOR and p38/MAPK signalling pathways in rat cardiomyocytes. Autophagy plays a protective role in AGE-induced apoptosis in cardiomyocytes.
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Hu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Liping
authors.initials: L
authors.lastname: Dou
authors.forename: Gang
authors.initials: G
authors.lastname: Bo
authors.forename: Jiale
authors.initials: J
authors.lastname: Wu
authors.forename: Shuwei
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D000071456:Sequestosome-1 Protein
chemical_list: D017127:Glycation End Products, Advanced; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D000071456:Sequestosome-1 Protein; C526109:Anxa3 protein, rat; C491079:Sqstm1 protein, rat