title: α-Lipoic acid protected cardiomyoblasts from the injury induced by sodium nitroprusside through ROS-mediated Akt/Gsk-3β activation.
abstract: It has been long noted that cardiac cell apoptosis provoked by excessive production of nitric oxide (NO) plays important roles in the pathogenesis of variant cardiac diseases. Attenuation of NO-induced injury would be an alternative therapeutic approach for the development of cardiac disorders. This study investigated the effects of α-lipoic acid (LA) on the injury induced by sodium nitroprusside (SNP), a widely used NO donor, in rat cardiomyoblast H9c2 cells. SNP challenge significantly decreased cell viability and increased apoptosis, as evidenced by morphological abnormalities, nuclear condensation and decline of mitochondrial potential (ΔΨm). These changes induced by SNP were significantly attenuated by LA pretreatment. Furthermore, LA pretreatment prevented the SNP-triggered suppression of Akt and Gsk-3β activation. Blockade of Akt activation with triciribin (API) completely abolished the cytoprotection of LA against SNP challenge. In addition, LA moderately increased intracellular ROS production. Interestingly, inhibition of ROS with N-acetylcysteine abrogated Akt/Gsk-3β activation and the LA-induced cytoprotection following SNP stimulation. Taken together, the results indicate that LA protected the SNP-induced injury in cardiac H9c2 cells through, at least in part, the activation of Akt/Gsk-3β signaling in a ROS-dependent mechanism.
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Department of Cardiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Surong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Surgery, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. Electronic address: liuli@njmu.edu.cn.
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; D002478:Cells, Cultured; D019610:Cytoprotection; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D009599:Nitroprusside; D008063:Thioctic Acid; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D000111:Acetylcysteine
keywords: Akt/Gsk-3β signaling; Apoptosis; Nitric oxide; Reactive oxygen species; Sodium nitroprusside; α-Lipoic acid