HS-1793 protects C2C12 cells from oxidative stress via mitochondrial function regulation

Molecular & Cellular Toxicology

article

Marquez, Jubert¹  Park, Nammi¹  Garcia, Maria Victoria Faith¹  Kim, Hyoung Kyu¹  Han, Jin¹ 

[1] National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Smart Marine Therapeutics Center, Cardiovascular and Metabolic Disease Center, Inje University;Department of Health Sciences and Technology, Graduate School of Inje University, College of Medicine, Inje University

关键词: Cachexia;    Cisplatin;    HS-1793;    Mitochondria;    Oxidative stress;   

DOI  :  10.1007/s13273-020-00090-w

来源: Korean Society of Toxicogenomics and Toxicoproteomics

【 摘 要 】

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.

【 授权许可】

Unknown