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Indole-6-carboxaldehyde prevents oxidative stress-induced mitochondrial dysfunction, DNA damage and apoptosis in C2C12 skeletal myoblasts by regulating the ROS-AMPK signaling pathway
Molecular & Cellular Toxicology ( IF 1.7 ) Pub Date : 2020-09-07 , DOI: 10.1007/s13273-020-00102-9
Cheol Park , Hyesook Lee , Shin-Hyung Park , Su Hyun Hong , Kyoung Seob Song , Hee-Jae Cha , Gi-Young Kim , Young-Chae Chang , Suhkmann Kim , Heui-Soo Kim , Yung Hyun Choi

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 H2O2-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 AMP-activated 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.



中文翻译:

吲哚-6-甲醛通过调节ROS-AMPK信号通路来预防氧化应激诱导的线粒体功能异常,DNA损伤和C2C12骨骼肌成肌细胞凋亡

背景

已知吲哚-6-甲醛(I6CA)是衍生自褐藻Sargassum thunbergii(Mertens)Kuntze的天然吲哚衍生物,具有多种药理活性。然而,尚未确定I6CA的抗氧化作用。

目的

这项研究旨在调查I6CA的保护作用及其潜在机制,以抵抗C2C12小鼠骨骼肌成肌细胞中氧化应激诱导的损伤。

结果

研究结果表明,用I6CA进行预处理可通过阻止细胞内活性氧(ROS)的生成来保护过氧化氢(H 2 O 2)诱导的细胞毒性和DNA损伤。I6CA还通过阻止线粒体膜电位的丧失和细胞色素c的胞质释放,降低Bax / Bcl-2表达的速率并降低胱天蛋白酶的活性,来显着抑制C2C12细胞抵抗H 2 O 2诱导的凋亡。此外,I6CA显着减弱了H 2 O 2诱导的ATP含量下降,并恢复了H 2 O 2诱导的AMP活化蛋白激酶(AMPK)活化。但是,I6CA对H 2 O 2的细胞保护作用被化合物C(一种特定的AMPK信号传导阻滞剂)消除了。

结论

当前结果表明,I6CA能够通过至少保留通过ROS-AMPK信号通路介导的线粒体稳态来保护C2C12成肌细胞DNA损伤和细胞凋亡免受氧化应激。

更新日期:2020-09-08
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