title: Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway.
abstract: Previous studies showed that the accumulation of advanced glycation end products (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However, the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes remains unknown.
  
  
  METHODS
  Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mTOR pathway were applied to cells, respectively.
  
  
  RESULTS
  AGEs administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes, increased the number of autophagic vacuoles and impaired the cell viability in dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE. Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I and inhibited the cellular autophagy, accompanied by the reactivation of PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on cardiomyocytes.
  
  
  CONCLUSIONS
  This study provides evidence that AGEs induces cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR pathway via RAGE.
authors.affiliation: Department of Cardiology, Hangzhou Hospital, Nanjing Medical University & Hangzhou First Municipal Hospital, Hangzhou 310006, China. beckhxw007@gmail.com.
authors.forename: Xuwei
authors.initials: X
authors.lastname: Hou
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Hu
authors.forename: Hanying
authors.initials: H
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Shunrong
authors.initials: S
authors.lastname: Zhang
authors.forename: Yigang
authors.initials: Y
authors.lastname: Zhong
authors.forename: Xiuying
authors.initials: X
authors.lastname: He
authors.forename: Ningfu
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D058570:TOR Serine-Threonine Kinases; C546845:mTOR protein, rat
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