title: Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes.
abstract: Oxidative stress is a key factor in stimulating the expression of atrogenes, which are muscle atrophy-related ubiquitin ligases, in skeletal muscle, and it induces muscle atrophy during unloading. However, the effects of antioxidative nutrients on atrogene expression have not been demonstrated. We report on the inhibitory effects of polyphenols, such as epicatechin (EC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) and quercetin, on atrogene expression up-regulated by three dimensional (3D)-clinorotation or glucocorticoid. These treatments markedly elevated the expression of atrogenes, including atrogin-1 and MuRF-1, in mouse C2C12 myoblasts and myotubes. Interestingly, EC, ECg, EGCg and quercetin significantly decreased the expression of atrogin-1 and MuRF-1 up-regulated by 3D-clinorotation, whereas they hardly affected atrogene expression induced by dexamethasone. ERK signaling is a well known MAPK pathway to mediate oxidative stress. Therefore, we also investigated the effect of these polyphenols on phosphorylation of ERK in C2C12 myotubes. As expected, EC, ECg, EGCg, and quercetin significantly suppressed phosphorylation of ERK, corresponding to the up-regulation of atrogenes induced by 3D-clinorotation. These results suggest that antioxidative nutrients, such as catechins and quercetin, suppress atrogene expression in skeletal muscle cells, possibly through the inhibition of ERK signaling. Thus, catechins and quercetin may prevent unloading-mediated muscle atrophy.
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School, Japan.
authors.forename: Dalia Ismaeil Ibrahim
authors.initials: DI
authors.lastname: Hemdan
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirasaka
authors.forename: Reiko
authors.initials: R
authors.lastname: Nakao
authors.forename: Shohei
authors.initials: S
authors.lastname: Kohno
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kagawa
authors.forename: Tomoki
authors.initials: T
authors.lastname: Abe
authors.forename: Akiko
authors.initials: A
authors.lastname: Harada-Sukeno
authors.forename: Yuushi
authors.initials: Y
authors.lastname: Okumura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D059808:Polyphenols; D011794:Quercetin / Q000494:pharmacology; D012399:Rotation / Q000009:adverse effects*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D005938:Glucocorticoids; D009124:Muscle Proteins; D010636:Phenols; D059808:Polyphenols; D000070584:Tripartite Motif Proteins; D003907:Dexamethasone; D002392:Catechin; C062669:epicatechin gallate; D011794:Quercetin; C045651:epigallocatechin gallate; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D048049:Extracellular Signal-Regulated MAP Kinases