Asiatic acid inhibits lactate-induced cardiomyocyte apoptosis through the regulation of the lactate signaling cascade

Gao,Changzheng; Wang,Fen; Wang,Zhiqiang; Zhang,Jing; Yang,Xiangjun

doi:10.3892/ijmm.2016.2783

Asiatic acid inhibits lactate-induced cardiomyocyte apoptosis through the regulation of the lactate signaling cascade

Authors:
- Changzheng Gao
- Fen Wang
- Zhiqiang Wang
- Jing Zhang
- Xiangjun Yang
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Cardiology, The Affiliated Hospital of Jiangnan University, Wuxi 4th People's Hospital, Wuxi, Jiangsu 214062, P.R. China, Department of Cardiothoracic Surgery, The Affiliated Hospital of Jiangnan University, Wuxi 4th People's Hospital, Wuxi, Jiangsu 214062, P.R. China
Published online on: October 20, 2016 https://doi.org/10.3892/ijmm.2016.2783
Pages: 1823-1830

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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.

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