Indole-6-carboxaldehyde prevents oxidative stress-induced mitochondrial dysfunction, DNA damage and apoptosis in C2C12 s
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ORIGINAL ARTICLE
Indole‑6‑carboxaldehyde prevents oxidative stress‑induced mitochondrial dysfunction, DNA damage and apoptosis in C2C12 skeletal myoblasts by regulating the ROS‑AMPK signaling pathway Cheol Park1 · Hyesook Lee2,3 · Shin‑Hyung Park4 · Su Hyun Hong2,3 · Kyoung Seob Song5 · Hee‑Jae Cha6 · Gi‑Young Kim7 · Young‑Chae Chang8 · Suhkmann Kim9 · Heui‑Soo Kim10 · Yung Hyun Choi2,3 Accepted: 31 August 2020 © The Korean Society of Toxicogenomics and Toxicoproteomics 2020 2020
Abstract 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 H 2O2-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 AMPactivated 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. Keywords Indole-6-carboxaldehyde · Oxidative stress · DNA damage · Apoptosis · AMPK
Introduction Muscles require a large amount of oxygen due to the high energy demand for contractile activity and are one of the most vulnerable organs for oxidative stress, characterized by the overproduction of reactive oxygen species (ROS). Myoblasts are embryonic precursors of muscle cells produced by tissue-resident stem cells called satellite or muscle stem cells. They differentiate into muscle cells through myogenesis, a process that is fused to multi-nucleated myotubes (Sambasivan and Tajbakhsh 2015; Chang and Rudnicki 2014). The role of ROS in myogenic differentiation is complicated by a wide range of cellular responses depending * Yung Hyun Choi [email protected] Extended author information available on the last page of the article
on the level of ROS. At an appropriate level, ROS regulate many cellular signaling pathways, including myogenic differentiation and biosynthetic metabolism, but high levels of ROS are closely related to impaired myogenesis (Sandiford et al. 2014; Sestili et al. 2009; Hansen et al. 2007). In addition, excess ROS in myobl
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