Skeletal Muscle Laboratory, Institute of Integrated and Honors Studies, Kurukshetra University, Kurukshetra, Haryana 136119, India.
Laboratory of Infection Biology and Translational Research, Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India.
Biochim Biophys Acta Gen Subj. 2020 Oct;1864(10):129676. doi: 10.1016/j.bbagen.2020.129676. Epub 2020 Jul 7.
Oxidative stress is crucial player in skeletal muscle atrophy pathogenesis. S-allyl cysteine (SAC), an organosulfur compound of Allium sativum, possesses broad-spectrum properties including immuno- and redox-modulatory impact. Considering the role of SAC in regulating redox balance, we hypothesize that SAC may have a protective role in oxidative-stress induced atrophy.
C2C12 myotubes were treated with HO (100 μM) in the presence or absence of SAC (200 μM) to study morphology, redox status, inflammatory cytokines and proteolytic systems using fluorescence microscopy, biochemical analysis, real-time PCR and immunoblotting approaches. The anti-atrophic potential of SAC was confirmed in denervation-induced atrophy model.
SAC pre-incubation (4 h) could protect the myotube morphology (i.e. length/diameter/fusion index) from atrophic effects of HO. Lower levels of ROS, lipid peroxidation, oxidized glutathione and altered antioxidant enzymes were observed in HO-exposed cells upon pre-treatment with SAC. SAC supplementation also suppressed the rise in cytokines levels (TWEAK/IL6/myostatin) caused by HO. SAC treatment also moderated the degradation of muscle-specific proteins (MHCf) in the HO-treated myotubes supported by lower induction of diverse proteolytic systems (i.e. cathepsin, calpain, ubiquitin-proteasome E3-ligases, caspase-3, autophagy). Denervation-induced atrophy in mice illustrates that SAC administration alleviates the negative effects (i.e. mass loss, decreased cross-sectional area, up-regulation of proteolytic systems, and degradation of total/specific protein) of denervation on muscles.
SAC exerts significant anti-atrophic effects to protect myotubes from HO-induced protein loss and myofibers from denervation-induced muscle loss, due to the prevention of elevated proteolytic systems and inflammatory/oxidative molecules.
The results signify the potential of SAC against muscle atrophy.
氧化应激是骨骼肌萎缩发病机制中的关键因素。S-烯丙基半胱氨酸（SAC）是大蒜中的一种有机硫化合物，具有广泛的特性，包括免疫和氧化还原调节作用。考虑到 SAC 在调节氧化还原平衡中的作用，我们假设 SAC 可能在氧化应激诱导的萎缩中具有保护作用。
用 HO（100μM）处理 C2C12 肌管，并在存在或不存在 SAC（200μM）的情况下，使用荧光显微镜、生化分析、实时 PCR 和免疫印迹方法研究形态、氧化还原状态、炎症细胞因子和蛋白水解系统。在去神经诱导的萎缩模型中证实了 SAC 的抗萎缩潜力。
SAC 预孵育（4 小时）可防止 HO 对肌管形态（即长度/直径/融合指数）的萎缩作用。在 HO 暴露的细胞中，SAC 预处理观察到 ROS、脂质过氧化、氧化型谷胱甘肽和抗氧化酶水平降低。SAC 补充还抑制了 HO 引起的细胞因子水平（TWEAK/IL6/myostatin）的升高。SAC 处理还通过降低各种蛋白水解系统（即组织蛋白酶、钙蛋白酶、泛素-蛋白酶体 E3 连接酶、半胱天冬酶 3、自噬）的诱导，适度调节了 HO 处理的肌管中肌肉特异性蛋白（MHCf）的降解。SAC 给药减轻了去神经对肌肉的负面影响（即质量损失、横截面积减小、蛋白水解系统上调以及总/特定蛋白降解），说明了 SAC 在小鼠去神经诱导的萎缩中的作用。
SAC 发挥显著的抗萎缩作用，可防止 HO 诱导的蛋白丢失和去神经诱导的肌纤维丢失，这是由于防止了升高的蛋白水解系统和炎症/氧化分子。
这些结果表明 SAC 具有对抗肌肉萎缩的潜力。
