Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Division of Nephrology, TCM-Integrated Hospital, Southern Medical University, Guangzhou 510280, China.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Int Immunopharmacol. 2014 Apr;19(2):206-13. doi: 10.1016/j.intimp.2014.02.002. Epub 2014 Feb 15.
Muscle atrophy poses a serious concern to patients inflicted with inflammatory diseases. There is now increasing evidence which suggests a vital role for tumor necrosis factor alpha (TNF-α) in muscle pathology associated with impairment of differentiation and muscle wasting. Resveratrol has been an ascribed inhibitory effect on glucocorticoid-induced muscle atrophy in vitro, but the influence of resveratrol on the growth of C2C12 myotubes exposed to TNF-α remains unclear. The present study aimed to investigate the involvement of TNF-α in the regulation of skeletal muscle hypertrophy and atrophy, and the possibility to interfere with such modulations by means of resveratrol supplementation. For this purpose, C2C12 myotubes were treated with TNF-α in the presence or absence of resveratrol. Myotube treatment with TNF-α contributes to both hyperexpression of the muscle-specific ubiquitin ligase MAFbx and MuRF1, and these alterations are linked to a decrease of anabolic targets (Akt, mTOR, p70S6k and 4E-BP1) and an increase of catabolic targets (FoxO1, FoxO3a, MAFbx and MuRF1). Resveratrol supplementation effectively counteracts TNF-α induced muscle protein loss and reverses declining expression of Akt, mTOR, p70S6K, 4E-BP1and FoxO1, but exerts no influence of FoxO3a expression. Our study demonstrates that resveratrol can reverse the muscle cell atrophy caused by TNF-α through regulation of the Akt/mTOR/FoxO1 signaling pathways, followed by inhibition of the atrophy-related ubiquitin ligase. Our findings suggested that resveratrol could represent a possible strategy to improve muscle mass.
肌肉萎缩症给患有炎症性疾病的患者带来了严重的问题。越来越多的证据表明，肿瘤坏死因子-α（TNF-α）在与肌肉分化受损和肌肉消耗相关的肌肉病理学中起着至关重要的作用。白藜芦醇已被证明在体外具有抑制糖皮质激素诱导的肌肉萎缩的作用，但白藜芦醇对暴露于 TNF-α的 C2C12 肌管生长的影响尚不清楚。本研究旨在探讨 TNF-α在调节骨骼肌肥大和萎缩中的作用，以及通过白藜芦醇补充来干预这种调节的可能性。为此，在存在或不存在白藜芦醇的情况下，用 TNF-α处理 C2C12 肌管。TNF-α处理肌管会导致肌肉特异性泛素连接酶 MAFbx 和 MuRF1 的过度表达，这些变化与合成代谢靶标（Akt、mTOR、p70S6k 和 4E-BP1）的减少和分解代谢靶标（FoxO1、FoxO3a、MAFbx 和 MuRF1）的增加有关。白藜芦醇补充有效地抵消了 TNF-α诱导的肌肉蛋白损失，并逆转了 Akt、mTOR、p70S6K、4E-BP1 和 FoxO1 的表达下降，但对 FoxO3a 的表达没有影响。我们的研究表明，白藜芦醇可以通过调节 Akt/mTOR/FoxO1 信号通路来逆转 TNF-α引起的肌肉细胞萎缩，从而抑制与萎缩相关的泛素连接酶。我们的研究结果表明，白藜芦醇可能是一种改善肌肉质量的策略。
