title: Resveratrol prevents TNF-α-induced muscle atrophy via regulation of Akt/mTOR/FoxO1 signaling in C2C12 myotubes.
abstract: 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.
authors.affiliation: 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.
authors.forename: Dong-Tao
authors.initials: DT
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yin
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Division of Nephrology, TCM-Integrated Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Pei-Jia
authors.initials: PJ
authors.lastname: Lv
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: 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. Electronic address: weilianbo@163.com.
authors.forename: Lian-Bo
authors.initials: LB
authors.lastname: Wei
mesh_terms: D000818:Animals; D002460:Cell Line; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009133:Muscular Atrophy / Q000188:drug therapy / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D000077185:Resveratrol; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D009124:Muscle Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013267:Stilbenes; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000077185:Resveratrol
keywords: Muscle atrophy; Resveratrol; TNF-α