HS-1793 protects C2C12 cells from oxidative stress via mitochondrial function regulation
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ORIGINAL ARTICLE
HS‑1793 protects C2C12 cells from oxidative stress via mitochondrial function regulation Jubert Marquez1,2 · Nammi Park1 · Maria Victoria Faith Garcia1,2 · Hyoung Kyu Kim1,2 · Jin Han1,2 Received: 11 January 2019 / Accepted: 10 June 2020 © The Korean Society of Toxicogenomics and Toxicoproteomics 2020 2020
Abstract Background HS1793, a novel analogue of resveratrol, was previously determined to be more potent at lower dosages by improving mitochondrial function and increased mitochondrial biogenesis-related proteins. In this study, we focused on targeting the mitochondria to address muscle wasting with HS-1793. Method Dosage screening was performed by evaluating for cytotoxicity and cell proliferation. Mitochondrial mass, mitochondrial membrane potential (Δψm), reactive oxygen species (ROS) level, and mitochondria biogenesis-regulated genes and proteins were analyzed to determine the effects on mitochondrial biogenesis. Results HS-1793 reduced ROS generation, but treatment did not interfere with cellular viability at low dosages. HS-1793 also regulated mitochondrial function by increasing cellular and mitochondrial ATP synthesis function, stabilizing Δψm and decreasing ROS. More importantly, these dysfunction in these parameters were ameliorated by HS-1793 in a simulated oxidative stress model with tBHP. We also observed increase in mitochondrial mass and upregulation in vital mitochondrial biogenesis-related gene PGC1-α as a response to HS-1793 treatment. Moreover, phosphorylation of AKT and mTOR proteins, which are considered as regulators of skeletal muscle function were also increased during the treatment. Finally, HS-1793 also demonstrated protective effects against cisplatin-induced skeletal muscle cell injury by increasing expression of mitochondrial biogenesis-relate markers. Conclusion Taken altogether, it shows the viability of HS-1793 as a compound that can restore mitochondrial function and render protection in skeletal muscle cells, especially during high oxidative stress levels. Keywords Cachexia · Cisplatin · HS-1793 · Mitochondria · Oxidative stress
Introduction
Jubert Marquez and Nammi Park contributed equally to the project. * Jin Han [email protected] 1
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, BK21 Plus Project Team, College of Medicine, Smart Marine Therapeutics Center, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Republic of Korea
Department of Health Sciences and Technology, BK21 Plus Project Team, Graduate School of Inje University, College of Medicine, Inje University, Busan 47392, Republic of Korea
2
Mitochondrial dysfunction has been well attributed to skeletal muscle pathologies, brought about by changes in mitochondrial energetics or oxidative damage (Abrigo et al. 2019). Mitochondria not only appear susceptible to damage mediated by increased stress, but also play significant roles in the regulation of cell function (Ballinger 2005). Cachexia often accompanies skeletal muscle
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