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.

中文翻译：

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HS-1793通过调节线粒体功能来保护C2C12细胞免受氧化应激

背景

HS1793，一种白藜芦醇的新型类似物，先前已被确定通过改善线粒体功能和增加与线粒体生物发生有关的蛋白质而在较低剂量下更有效。在这项研究中，我们专注于针对线粒体以解决HS-1793造成的肌肉浪费。

方法

通过评估细胞毒性和细胞增殖进行剂量筛选。分析了线粒体质量，线粒体膜电位（Δψm ），活性氧（ROS）水平以及线粒体生物发生调节基因和蛋白质，以确定对线粒体生物发生的影响。

结果

HS-1793减少了ROS的产生，但低剂量治疗不会干扰细胞活力。HS-1793还通过增加细胞和线粒体ATP合成功能，稳定Δψm和降低ROS来调节线粒体功能。更重要的是，在带有tBHP的模拟氧化应激模型中，HS-1793改善了这些参数的功能障碍。我们还观察到，作为对HS-1793治疗的响应，线粒体质量增加和重要的线粒体生物发生相关基因PGC1-α上调。此外，在治疗过程中还增强了被认为是骨骼肌功能调节剂的AKT和mTOR蛋白的磷酸化。最后，

结论

总而言之，它显示出HS-1793作为一种化合物的活力，该化合物可以恢复线粒体功能并在骨骼肌细胞中提供保护，尤其是在高氧化应激水平下。