S-allyl cysteine: A potential compound against skeletal muscle atrophy.,Biochimica et Biophysica Acta (BBA) - General Subjects

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S-allyl cysteine: A potential compound against skeletal muscle atrophy.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2020-07-07 , DOI: 10.1016/j.bbagen.2020.129676
Prachi Gupta ₁ , Vikas Dutt ₁ , Nirmaljeet Kaur ₁ , Priya Kalra ₂ , Sanjeev Gupta ₁ , Anita Dua ₁ , Rajesh Dabur ₃ , Vikram Saini ₂ , Ashwani Mittal ₁

Affiliation

Background

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.

Methods

C2C12 myotubes were treated with H₂O₂ (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.

Results

SAC pre-incubation (4 h) could protect the myotube morphology (i.e. length/diameter/fusion index) from atrophic effects of H₂O₂. Lower levels of ROS, lipid peroxidation, oxidized glutathione and altered antioxidant enzymes were observed in H₂O₂-exposed cells upon pre-treatment with SAC. SAC supplementation also suppressed the rise in cytokines levels (TWEAK/IL6/myostatin) caused by H₂O₂. SAC treatment also moderated the degradation of muscle-specific proteins (MHCf) in the H₂O₂-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.

Conclusions

SAC exerts significant anti-atrophic effects to protect myotubes from H₂O₂-induced protein loss and myofibers from denervation-induced muscle loss, due to the prevention of elevated proteolytic systems and inflammatory/oxidative molecules.

General significance

The results signify the potential of SAC against muscle atrophy.

中文翻译：

S-烯丙基半胱氨酸：一种潜在的抗骨骼肌萎缩的化合物。

背景

氧化应激是骨骼肌萎缩发病机理的关键因素。S-烯丙基半胱氨酸（SAC）是大蒜的有机硫化合物，具有广谱特性，包括免疫调节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可能在氧化应激引起的萎缩中起保护作用。

方法

在存在或不存在SAC（200μM）的情况下，用H ₂ O ₂（100μM）处理C2C12肌管，以使用荧光显微镜，生化分析，实时PCR和免疫印迹方法研究形态，氧化还原状态，炎性细胞因子和蛋白水解系统。在去神经引起的萎缩模型中证实了SAC的抗萎缩潜力。

结果

SAC预孵育（4 h）可以保护肌管形态（即长度/直径/融合指数）免受H ₂ O _2的萎缩作用。用SAC预处理后，在暴露于H ₂ O _2的细胞中观察到较低水平的ROS，脂质过氧化，氧化型谷胱甘肽和抗氧化酶的改变。补充SAC还抑制了H ₂ O ₂引起的细胞因子水平（TWEAK / IL6 / myostatin）的升高。SAC处理在H也缓和肌肉特异性蛋白质（MHCf）的降解_2个Ó ₂由不同的蛋白水解系统的下感应支持-处理的肌管（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）。去神经引起的小鼠萎缩说明，SAC给药减轻了神经去神经作用的负面影响（即质量损失，横截面积减小，蛋白水解系统上调和总/特异性蛋白质降解）。