title: Cell hypertrophy and MEK/ERK phosphorylation are regulated by glyceraldehyde-derived AGEs in cardiomyocyte H9c2 cells.
abstract: Diabetic cardiomyopathy has been shown to promote hypertrophy, leading to heart failure. Recent studies have reported a correlation between diabetic cardiomyopathy and oxidative stress, suggesting that the accumulation of advanced glycation end products (AGEs) induces the production of reactive oxygen species (ROS). In a clinical setting, AGEs have been shown to increase the risk of cardiovascular disease; however, the relationship between AGEs and cardiac hypertrophy remains unclear. This study sought to identify the role of AGEs in cardiac hypertrophy by treating H9c2 cells with glyceraldehyde-derived AGEs (200 μg/ml) or H2O2 (50 μM) for 96 h. Our results demonstrate that AGEs significantly increased protein levels and cell size. These effects were effectively blocked with PD98059 (10 μM; MEK/ERK inhibitor) pretreatment, suggesting that AGEs caused cell hypertrophy via the MEK/ERK pathway. We then treated cells with AGEs and H2O2 for 0-120 min and employed the Odyssey infrared imaging system to detect MEK/ERK phosphorylation. Our results show that AGEs up-regulated MEK/ERK phosphorylation. However, this effect was blocked by NAC (5 mM; ROS inhibitor), indicating that AGEs regulate MEK/ERK phosphorylation via ROS. Our findings suggest that glyceraldehyde-derived AGEs are closely related to cardiac hypertrophy and further identify a molecular mechanism underlying the promotion of diabetic cardiomyopathy by AGEs.
authors.affiliation: Department of Bioscience and Technology, Graduate Institute of Medical Science, College of Health Science, Innovate Research Center of Medicine, Chang Jung Christian University, Tainan, Taiwan, ROC. syko@mail.cjcu.edu.tw
authors.forename: Shun-Yao
authors.initials: SY
authors.lastname: Ko
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Lin
authors.forename: Tzong-Ming
authors.initials: TM
authors.lastname: Shieh
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Ko
authors.forename: Hong-I
authors.initials: HI
authors.lastname: Chen
authors.forename: Tzong-Cherng
authors.initials: TC
authors.lastname: Chi
authors.forename: Shu-Shing
authors.initials: SS
authors.lastname: Chang
authors.forename: Yi-Chiang
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology*; D005985:Glyceraldehyde / Q000378:metabolism*; D006984:Hypertrophy / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D005985:Glyceraldehyde; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases