Indole-6-carboxaldehyde prevents oxidative stress-induced mitochondrial dysfunction, DNA damage and apoptosis in C2C12 skeletal myoblasts by regulating the ROS-AMPK signaling pathway

Molecular & Cellular Toxicology

article

Park, Cheol¹  Kim, Heui-Soo²  Choi, Yung Hyun³  Lee, Hyesook³  Park, Shin-Hyung⁵  Hong, Su Hyun³  Song, Kyoung Seob⁶  Cha, Hee-Jae⁷  Kim, Gi-Young⁸  Chang, Young-Chae⁹  Kim, Suhkmann^1,10 

[1] Division of Basic Sciences, College of Liberal Studies, Dong-eui University;Department of Biological Sciences, College of Natural Sciences, Pusan National University;Anti-Aging Research Center, Dong-eui University;Department of Biochemistry, College of Korean Medicine, Dong-eui University;Department of Pathology, College of Korean Medicine, Dong-eui University;Department of Cell Biology, Kosin University College of Medicine;Department of Parasitology and Genetics, Kosin University College of Medicine;Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University;Engineering and Department of Medicine Catholic, Research Institute of Biomedical, University of Daegu School of Medicine;Department of Chemistry, College of Natural Sciences, Pusan National University

关键词: Indole-6-carboxaldehyde;    Oxidative stress;    DNA damage;    Apoptosis;    AMPK;   

DOI  :  10.1007/s13273-020-00102-9

来源: Korean Society of Toxicogenomics and Toxicoproteomics

【 摘 要 】

Background Indole-6-carboxaldehyde (I6CA), a natural indole derivative derived from the brown algae Sargassum thunbergii (Mertens) Kuntze, is known to have several pharmacological activities. However, the antioxidant effects of I6CA have not been identified. Objective The study aimed to investigate the protective effect of I6CA and its underlying mechanism against oxidative stress-induced damage in C2C12 mouse skeletal myoblasts. Results The findings revealed that pretreatment with I6CA protected hydrogen peroxide (H2O2)-induced cytotoxicity and DNA damage through blockage of intracellular reactive oxygen species (ROS) generation. I6CA also significantly suppressed C2C12 cells against H2O2-induced apoptosis by preventing loss of mitochondrial membrane potential and cytosolic release of cytochrome c, decreasing the rate of Bax/Bcl-2 expression and reducing the activity of caspases. In addition, I6CA markedly attenuated the decrease in ATP content induced by H2O2 and restored H2O2-induced activation of AMP-activated protein kinase (AMPK). However, the cytoprotective effects of I6CA against H2O2 were eliminated by compound C, a specific AMPK signaling blocker. Conclusion The current results indicate that I6CA was able to protect C2C12 myoblast DNA damage and apoptosis from oxidative stress by at least preserving mitochondrial homeostasis mediated through the ROS-AMPK signaling pathway.

【 授权许可】

Unknown