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KMID : 1034820200160040359
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Molecular & Cellular Toxicology
2020 Volume.16 No. 4 p.359 ~ p.365
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HS-1793 protects C2C12 cells from oxidative stress via mitochondrial function regulation
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Marquez Jubert
Park Nam-Mi
Garcia Maria Victoria Faith
Kim Hyoung-Kyu
Han Jin
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Abstract
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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.
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KEYWORD
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Cachexia, Cisplatin, HS-1793, Mitochondria, Oxidative stress
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