Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes

Hemdan, Dalia I.; Hirasaka, Katsuya; Nakao, Reiko; Kohno, Shohei; Kagawa, Sachiko; Abe, Tomoki; Harada-Sukeno, Akiko; Okumura, Yuushi; Nakaya, Yutaka; Terao, Junji; Nikawa, Takeshi

doi:10.2152/jmi.56.26

Cited by 50 publications

(27 citation statements)

References 30 publications

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“…In C2C12 myotubes ERK activation resulted in reduced myotube size [16], while ERK inhibition induced a hypertrophic phenotype similar to that elicited by IGF-1 [16]. Similarly, C2C12 myotube cultures subjected to 3D-clinorotation showed an overexpression of both atrogin-1 and MuRF1 ubiquitin ligases, associated with increased levels of phosphorylated ERK [26].…”

Section: Discussionmentioning

confidence: 85%

Muscle Wasting and Impaired Myogenesis in Tumor Bearing Mice Are Prevented by ERK Inhibition

et al. 2010

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BackgroundThe onset of cachexia is a frequent feature in cancer patients. Prominent characteristic of this syndrome is the loss of body and muscle weight, this latter being mainly supported by increased protein breakdown rates. While the signaling pathways dependent on IGF-1 or myostatin were causally involved in muscle atrophy, the role of the Mitogen-Activated-Protein-Kinases is still largely debated. The present study investigated this point on mice bearing the C26 colon adenocarcinoma.Methodology/Principal FindingsC26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p)-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNFα-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059.Conclusions/SignificanceThese results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target.

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Section: Discussionmentioning

confidence: 85%

Muscle Wasting and Impaired Myogenesis in Tumor Bearing Mice Are Prevented by ERK Inhibition

et al. 2010

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“…EC is found in cacao beans and has the highest content of catechins among foods [7] and is made up circa 2–5% of total dry weight of green tea [8]. Anti-oxidative nutrients including EC and catechin, suppress atrogene expression in skeletal muscle cells, possibly through the inhibition of ERK signaling, resulting in prevention of unloading-mediated muscle atrophy [9]. It has been reported that EC, the main component present in dark chocolate, reduces the risk to develop cardiovascular diseases and myocardial injury [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Epicatechin elicits MyoD-dependent myoblast differentiation and myogenic conversion of fibroblasts

Lee

Leem

et al. 2017

PLoS ONE

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Prevention of age-associated reduction in muscle mass and function is required to manage a healthy life. Supplemental (-)-Epicatechin (EC) appears to act as a potential regulator for muscle growth and strength. However, its cellular and molecular mechanisms as a potential muscle growth agent have not been studied well. In the current study, we investigated a role of EC in differentiation of muscle progenitors to gain the molecular insight into how EC regulates muscle growth. EC enhanced myogenic differentiation in a dose-dependent manner through stimulation of promyogenic signaling pathways, p38MAPK and Akt. EC treatment elevated MyoD activity by enhancing its heterodimerization with E protein. Consistently, EC also positively regulated myogenic conversion and differentiation of fibroblasts. In conclusion, EC has a potential as a therapeutic or nutraceutical remedy to treat degenerative muscle diseases or age-related muscle weakness.

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“…In in vitro assays, resveratrol reduced skeletal muscle atrophy, enhanced glucose uptake, inhibited NFkB-mediated protein degradation, and improved muscle function [53], [54], [55]. EGCG reduced oxidative stress in C2C12 cells, thereby attenuating the expression of atrogin-1 and MuRF-1, two muscle atrophy-related ubiquitin ligases [52]. EGCG also abrogated the expression of lipofuscin, a marker of oxidative stress, when subcutaneously injected into mdx mice from birth, resulting in improved muscle function, force, and physiology [56].…”

Section: Resultsmentioning

confidence: 98%

“…Two natural products that reduce oxidative stress are resveratrol, present in red wine and peanuts [51] and epigallocatechin-3-gallate (EGCG), the primary polyphenol in green tea [52]. In in vitro assays, resveratrol reduced skeletal muscle atrophy, enhanced glucose uptake, inhibited NFkB-mediated protein degradation, and improved muscle function [53], [54], [55].…”

Section: Resultsmentioning

confidence: 99%

Identification of Retinoic Acid in a High Content Screen for Agents that Overcome the Anti-Myogenic Effect of TGF-Beta-1

Krueger

Hoffmann

2010

PLoS ONE

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BackgroundTransforming growth factor beta 1 (TGF-β1) is an inhibitor of muscle cell differentiation that is associated with fibrosis, poor regeneration and poor function in some diseases of muscle. When neutralizing antibodies to TGF-β1 or the angiotensin II inhibitor losartan were used to reduce TGF-β1 signaling, muscle morphology and function were restored in mouse models of Marfan Syndrome and muscular dystrophy. The goal of our studies was to identify additional agents that overcome the anti-myogenic effect of TGF-β1.Methodology/Principal FindingsA high-content cell-based assay was developed in a 96-well plate format that detects the expression of myosin heavy chain (MHC) in C2C12 cells. The assay was used to quantify the dose-dependent responses of C2C12 cell differentiation to TGF-β1 and to the TGF-β1 Type 1 receptor kinase inhibitor, SB431542. Thirteen agents previously described as promoting C2C12 differentiation in the absence of TGF-β1 were screened in the presence of TGF-β1. Only all-trans retinoic acid and 9-cis retinoic acid allowed a maximal level of C2C12 cell differentiation in the presence of TGF-β1; the angiotensin-converting enzyme inhibitor captopril and 10 nM estrogen provided partial rescue. Vitamin D was a potent inhibitor of retinoic acid-induced myogenesis in the presence of TGF-β1. TGF-β1 inhibits myoblast differentiation through activation of Smad3; however, retinoic acid did not inhibit TGF-β1-induced activation of a Smad3-dependent reporter gene in C2C12 cells.Conclusions/SignificanceRetinoic acid alleviated the anti-myogenic effect of TGF-β1 by a Smad3-independent mechanism. With regard to the goal of improving muscle regeneration and function in individuals with muscle disease, the identification of retinoic acid is intriguing in that some retinoids are already approved for human therapy. However, retinoids also have well-described adverse effects. The quantitative, high-content assay will be useful to screen for less-toxic retinoids or combinations of agents that promote myoblast differentiation in the presence of TGF-β1.

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Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes

Cited by 50 publications

References 30 publications

Muscle Wasting and Impaired Myogenesis in Tumor Bearing Mice Are Prevented by ERK Inhibition

Muscle Wasting and Impaired Myogenesis in Tumor Bearing Mice Are Prevented by ERK Inhibition

Epicatechin elicits MyoD-dependent myoblast differentiation and myogenic conversion of fibroblasts

Identification of Retinoic Acid in a High Content Screen for Agents that Overcome the Anti-Myogenic Effect of TGF-Beta-1

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