Effects of alpha-ketoisocaproate in oxidative stress-induced C2C12 myotubes via inhibition of p38 MAPK and ERK1/2

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-02-21 DOI:10.1016/j.bbrep.2025.101955

Pooreum Lim, Sang Woo Woo, Jihye Han, Young Lim Lee, Jae Ho Shim, Hyeon Soo Kim

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Abstract

Sarcopenia is an age-related muscle atrophy characterized by decreased muscle mass and function. However, potential treatments to alleviate sarcopenia remain limited. In this study, we investigated the effects of α-ketoisocaproate (KIC) on C2C12 differentiation and reactive oxygen species (ROS)-induced atrophy in C2C12 myotubes. We demonstrated that KIC upregulates the expression of myogenic differentiation factors, including myoblast determination protein 1 (MyoD) and myogenin (MyoG), during C2C12 differentiation. Additionally, KIC enhanced the expression of myosin heavy chain (MHC) isoforms MHC1, MHC2b, and MHC2x in C2C12 myotubes. KIC suppressed the decreased MyoG expression and the increase in the muscle atrophy-related factor, muscle atrophy F-box (MAFbx), in ROS-induced C2C12 myotubes. In addition, it restored the reduced expression of MHC and the diameter of C2C12 myotubes. We showed that KIC alleviated muscle atrophy by inhibiting mitogen-activated protein kinase (MAPK) signaling pathways, such as p38 MAPK and extracellular signal-regulated kinase 1/2 (ERK1/2). These findings suggest that KIC may serve as a potential therapeutic agent for ameliorating sarcopenia by inhibiting MAPK signaling in ROS-induced skeletal muscle cells.

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肌肉疏松症是一种与年龄有关的肌肉萎缩症，其特点是肌肉质量和功能下降。然而，缓解肌肉疏松症的潜在治疗方法仍然有限。在这项研究中，我们研究了α-酮异己酸盐（KIC）对C2C12分化和活性氧（ROS）诱导的C2C12肌管萎缩的影响。我们证实，在C2C12分化过程中，KIC能上调肌原分化因子的表达，包括肌母细胞决定蛋白1（MyoD）和肌原蛋白（MyoG）。此外，KIC还能增强C2C12肌细胞管中肌球蛋白重链（MHC）同工酶MHC1、MHC2b和MHC2x的表达。在 ROS 诱导的 C2C12 肌管中，KIC 抑制了 MyoG 表达的减少和肌肉萎缩相关因子肌肉萎缩 F-box (MAFbx) 的增加。此外，它还能恢复减少的 MHC 表达和 C2C12 肌管的直径。我们发现，KIC通过抑制有丝分裂原激活蛋白激酶（MAPK）信号通路，如p38 MAPK和细胞外信号调节激酶1/2（ERK1/2），缓解了肌肉萎缩。这些研究结果表明，通过抑制 ROS 诱导的骨骼肌细胞中的 MAPK 信号传导，KIC 可作为一种潜在的治疗药物来改善肌肉疏松症。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.