title: α-Lipoic acid increases tolerance of cardiomyoblasts to glucose/glucose oxidase-induced injury via ROS-dependent ERK1/2 activation.
abstract: α-Lipoic acid (LA) has been shown to improve the diabetic cardiac symptoms. However, the underlying mechanisms have not been elucidated precisely. We have reported recently that LA potentially protected neurons from substance-induced apoptosis. We hypothesized that LA could attenuate cardiac cells death induced by oxidative stress derived from high glucose. To test this possibility, we examined the effects of LA on d-glucose/glucose oxidase (DG/GO, 30mM/5mU)-induced injury in rat cardiomyoblast H9c2 cells. We observed that LA pretreatment significantly increased cell viability in DG/GO-challenged cells. LA pretreatment also attenuated DG/GO-induced apoptosis as evidenced by decreases in both nuclear condensation and loss of mitochondrial potential. In addition, LA activated ERK1/2 and moderately increased ROS production. Blockade of ERK1/2 activation by PD98059 completely abolished LA-induced protection against DG/GO challenge. Inhibition of ROS by N-acetylcysteine abrogated LA-induced ERK1/2 activation and cytoprotection. Furthermore, we observed that the ROS production induced by LA was significantly slower and milder than that by DG/GO. Our results suggest that pretreatment with LA moderately increased ROS production to induce a preconditioning-like effect by ERK1/2 activation thereby increased tolerance of H9c2 cells to DG/GO challenge.
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Yao
authors.forename: Rongrong
authors.initials: R
authors.lastname: Li
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D005949:Glucose Oxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose; D000111:Acetylcysteine