title: Asiatic acid inhibits lactate-induced cardiomyocyte apoptosis through the regulation of the lactate signaling cascade.
abstract: The lactate signaling cascade has recently been linked to mitochondrial energy metabolism and cardiomyocyte apoptosis in several cardiovascular diseases. Asiatic acid (AA) exhibits a variety of pharmacological effects, including antioxidant and anti-apoptotic effects. In this study, we investigated the protective effects of AA against the lactate-induced apoptosis of cardiomyocytes, as well as its mechanisms of action. Neonatal rat cardiomyocytes were pre-treated with 20 µM AA for 24 h, followed by exposure to 20 mM lactate for a further 24 h. Cell viability was determined by a cell counting kit-8 (CCK-8) assay. Cell apoptosis, reactive oxygen species (ROS) levels and mitochondrial membrane potential (Δψm) were evaluated by flow cytometry or fluorescence microscopy. The expression levels of mitochondrial monocarboxylate transporter 1 (MCT1) and cytoplasmic cytochrome c, cleaved caspase-9 and caspase-3 were assayed by western blot analysis. Our results revealed that AA significantly inhibited lactate-induced apoptosis, intracellular ROS generation and the loss of Δψm. AA also increased the expression of mitochondrial MCT1 and reduced the expression of cytoplasmic cytochrome c, cleaved caspase-9 and caspase-3 in the lactate-stimulated cardiomyocytes. To the best of our knowledge, our data demonstrate for the first time that AA plays a cytoprotective role in lactate-induced apoptosis by regulating the lactate signaling cascade, involving the inhibition of oxidative stress and mitochondria-dependent caspase activation, as well as the upregulation of mitochondrial MCT1 expression.
authors: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Changzheng
authors: C
authors: Gao
authors: Department of Cardiology, The Affiliated Hospital of Jiangnan University, Wuxi 4th People's Hospital, Wuxi, Jiangsu 214062, P.R. China.
authors: Fen
authors: F
authors: Wang
authors: Department of Cardiothoracic Surgery, The Affiliated Hospital of Jiangnan University, Wuxi 4th People's Hospital, Wuxi, Jiangsu 214062, P.R. China.
authors: Zhiqiang
authors: Z
authors: Wang
authors: Department of Cardiology, The Affiliated Hospital of Jiangnan University, Wuxi 4th People's Hospital, Wuxi, Jiangsu 214062, P.R. China.
authors: Jing
authors: J
authors: Zhang
authors: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Xiangjun
authors: X
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019344:Lactic Acid / Q000378:metabolism* / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D019344:Lactic Acid; C017032:asiatic acid