Differential signalling mechanisms predisposing primary human skeletal muscle cells to altered proliferation and differentiation: roles of IGF-I and TNFα

Foulstone, Emily J.; Huser, Camille; Crown, Anna; Holly, Jeff M.P.; Stewart, Claire E.

doi:10.1016/j.yexcr.2003.10.034

Cited by 68 publications

(65 citation statements)

References 34 publications

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“…Activation of ERK1/2 might account for the increase in markers of myogenic differentiation that we previously reported in myotubes from women with PCOS (9), since this pathway plays an important role in the initiation and progression of human myoblast differentiation (48). It has been suggested that selective insulin resistance also contributes to the paradoxical effects of insulin on steroidogenesis in PCOS (1).…”

Section: Diabetes Vol 55 March 2006mentioning

confidence: 80%

Enhanced Mitogenic Signaling in Skeletal Muscle of Women With Polycystic Ovary Syndrome

et al. 2006

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Insulin resistance in polycystic ovary syndrome (PCOS) results from a postbinding defect in signaling. Insulin receptor and insulin receptor substrate (IRS)-1 serine hyperphosphorylation by an unidentified kinase(s) contributes to this defect. We investigated whether insulin resistance is selective, affecting metabolic but not mitogenic pathways, in skeletal muscle as it is in cultured skin fibroblasts in PCOS. Extracellular signal-regulated kinase (ERK)1/2 activation was increased in skeletal muscle tissue and in cultured myotubes basally and in response to insulin in women with PCOS compared with control women. Mitogen-activated/extracellular signal-regulated kinase kinase (MEK)1/2 was also activated in PCOS, whereas p38 mitogen-activated protein kinase phosphorylation and signaling from the insulin receptor to Grb2 was similar in both groups. The activity of p21Ras was decreased and Raf-1 abundance increased in PCOS, suggesting that altered mitogenic signaling began at this level. MEK1/2 inhibition reduced IRS-1 Ser 312 phosphorylation and increased IRS-1 association with the p85 subunit of phosphatidylinositol 3-kinase in both groups. We conclude that in PCOS skeletal muscle, 1) mitogenic signaling is enhanced in vivo and in culture, 2) ERK1/2 activation inhibits association of IRS-1 with p85 via IRS-1 Ser 312 phosphorylation, and 3) ERK1/2 activation may play a role in normal feedback of insulin signaling and contribute to resistance to insulin's metabolic actions in PCOS. Diabetes 55: [751][752][753][754][755][756][757][758][759] 2006

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Section: Diabetes Vol 55 March 2006mentioning

confidence: 80%

Enhanced Mitogenic Signaling in Skeletal Muscle of Women With Polycystic Ovary Syndrome

et al. 2006

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“…TNF-α and IFN-γ reduce myosin expression in myotubes and murine skeletal muscle [5]. Recent data indicated that TNF-α alone or in combination with IFN-γ induced apoptosis in skeletal muscle and in differentiating myocytes [34]. In another study, IFN-γ was found to inhibit the TNF-α-induced apoptosis of murine myotubes, which makes this cytokine a potential tool in the therapy of muscle atrophy [35].…”

Section: Discussionmentioning

confidence: 99%

Treatment with TNF-α and IFN-γ alters the activation of SER/THR protein kinases and the metabolic response to IGF-I in mouse c2c12 myogenic cells

Grzelkowska-Kowalczyk¹,

Wieteska-Skrzeczyńska²

2010

Cellular and Molecular Biology Letters

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The aim of this study was to compare the effects of TNF-α, IL-1β and IFN-γ on the activation of protein kinase B (PKB), p70S6k, mitogen-activated protein kinase (MAPK) and p90rsk, and on IGF-I-stimulated glucose uptake and protein synthesis in mouse C2C12 myotubes. 100 nmol/l IGF-I stimulated glucose uptake in C2C12 myotubes by 198.1% and 10 ng/ml TNF-α abolished this effect. Glucose uptake in cells differentiated in the presence of 10 ng/ml IFN-γ increased by 167.2% but did not undergo significant further modification upon the addition of IGF-I. IGF-I increased the rate of protein synthesis by 249.8%. Neither TNF-α nor IFN-γ influenced basal protein synthesis, but both cytokines prevented the IGF-I effect. 10 ng/ml IL-1β did not modify either the basal or IGF-I-dependent glucose uptake and protein synthesis. With the exception of TNF-α causing an 18% decrease in the level of PKB protein, the cellular levels of PKB, p70S6k, p42MAPK, p44MAPK and p90rsk were not affected by the cytokines. IGF-I caused the phosphorylation of PKB (an approximate 8-fold increase above the basal value after 40 min of IGF-I treatment), p42MAPK (a 2.81-fold increase after 50 min), and the activation of p70S6k and p90rsk, manifesting as gel mobility retardation. In cells differentiated in the presence of TNF-α or IFN-γ, this IGF-I-mediated PKB and p70S6k phosphorylation was significantly diminished, and the increase in p42MAPK and p90rsk phosphorylation was prevented. The basal p42MAPK phosphorylation in C2C12 cells treated with IFN-γ was high and comparable with the activation of this kinase by IGF-I. Pretreatment of myogenic cells with IL-1β did not modify the IGF-I-stimulated phosphorylation of PKB, p70S6k, p42MAPK and p90rsk. In conclusion: i) TNF-α and IFN-γ, but not IL-1β, if present in the extracellular environment during C2C12 myoblast differentiation, prevent the stimulatory action of IGF-I on protein synthesis. ii) TNF-α- and IFN-γ-induced IGF-I resistance of protein synthesis could be associated with the decreased phosphorylation of PKB and p70S6k. iii) The activation of glucose uptake in C2C12 myogenic cells treated with IFN-γ is PKB independent. iv) The similar effects of TNF-α and IFN-γ on the signalling and action of IGF-I on protein synthesis in myogenic cells could suggest the involvement of both of these cytokines in protein loss in skeletal muscle.

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“…Differentiation experiments were initiated by washing with PBS, and transferring into Low Serum Media (LSM) composed of: DMEM plus 2 % hi horse serum, 1 %l-glutamine, and 1 % penicillin-streptomycin (both as above) in the absence or presence of TNF-α (20 ng ml−1). A dose extensively characterised by ourselves and others to be an inhibitor of differentiation in mouse and human muscle cells (Foulstone et al2001(Foulstone et al , 2003(Foulstone et al , 2004(Foulstone et al , 2010(Foulstone et al , 2011Stewart et al 2004;Tolosa et al 2005). C2C12 cells undergo spontaneous differentiation into myotubes on serum withdrawal, and do not require growth factor addition to stimulate the process (Blau et al 1985;Tollefsen et al1989).…”

Section: General Cell Culturementioning

confidence: 99%

“…Our group has further begun to elucidate potential epigenetic modulators of myoblast survival and differentiation (Saini et al2012), where activation of Sirtuin1 (histone deacetylase) reduced myoblast death and enabled differentiation in the presence of stress from TNF-α, a cytokine that is chronically up regulated in muscle loss conditions such as sarcopenia and cachexia. We have extensively shown that TNF-α impairs myoblast fusion/differentiation and myotube hypertrophy with corresponding reductions in myoD gene expression in mouse and human muscle cells (Meadows 2000;Foulstone 2001Foulstone , 2004Al-Shanti 2008;Saini 2008;Sharples 2010). Thus, together with the above studies, this perhaps provides compelling yet preliminary data suggesting that epigenetic mechanisms such as myoD methylation could be involved in TNF-α induced reduction in differentiation and myotube atrophy in muscle cells and potentially be involved in muscle cell programming/memory.…”

Section: Introductionmentioning

confidence: 99%

“…Higher TNF-α levels are strongly correlated with muscle loss, reduced strength and therefore morbidity and earlier mortality. We have extensively shown that TNF-α impairs regenerative capacity in mouse and human muscle derived stem cells (Meadows 2000;Foulstone 2001Foulstone , 2004Al-Shanti 2008;Saini 2008;Sharples 2010). We have also recently established an epigenetically mediated mechanism (SIRT1-histone deacetylase) regulating survival of myoblasts in the presence of TNF-α (Saini 2012).…”

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confidence: 99%

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Skeletal muscle cells possess a ‘memory’ of acute early life TNF-α exposure: role of epigenetic adaptation

et al. 2015

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Sufficient quantity and quality of skeletal muscle is required to maintain lifespan and healthspan into older age. The concept of skeletal muscle programming or memory has been suggested to contribute to accelerated muscle decline in the elderly in association with early life stress such as fetal malnutrition. Further, muscle cells in vitro appear to remember the in vivo environments from which they are derived (e.g. cancer, obesity, type II diabetes, physical inactivity and nutrient restriction). Tumour-necrosis factor alpha (TNF-α) is a pleiotropic cytokine that is chronically elevated in sarcopenia and cancer cachexia. Higher TNF-α levels are strongly correlated with muscle loss, reduced strength and therefore morbidity and earlier mortality. We have extensively shown that TNF-α impairs regenerative capacity in mouse and human muscle derived stem cells (Meadows 2000;Foulstone 2001Foulstone , 2004Al-Shanti 2008;Saini 2008;Sharples 2010). We have also recently established an epigenetically mediated mechanism (SIRT1-histone deacetylase) regulating survival of myoblasts in the presence of TNF-α (Saini 2012). We therefore wished to extend this work in relation to muscle memory of catabolic stimuli and the potential underlying epigenetic modulation of muscle loss. To enable this aim; C2C12 myoblasts were cultured in the absence or presence of early TNF-α (early proliferative lifespan) followed by 30 population doublings in the absence of TNF-α, prior to the induction of differentiation in low serum media (LSM) in the absence or presence of late TNF-α (late proliferative lifespan). The cells that received an early plus late lifespan dose of TNF-α exhibited reduced morphological (myotube number) and biochemical (creatine kinase activity) differentiation vs. control cells that underwent the same number of proliferative divisions but only a later life encounter with TNF-α. This suggested that muscle cells had a morphological memory of the acute early lifespan TNF-α encounter. Importantly, methylation of myoD CpG islands were increased in the early TNF-α cells, 30 population doublings later, suggesting that even after an acute encounter with TNF-α, the cells have the capability of retaining elevated methylation for at least 30 cellular divisions. Despite these fascinating findings, there were no further increases in myoD methylation or changes in its gene expression when these cells were exposed to a later TNF-α dose suggesting that this was not directly responsible for the decline in differentiation observed. In conclusion, data suggest that elevated myoD methylation is retained throughout muscle cells proliferative lifespan as result of early life TNF-α treatment and has implications for the epigenetic control of muscle loss.

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Differential signalling mechanisms predisposing primary human skeletal muscle cells to altered proliferation and differentiation: roles of IGF-I and TNFα

Cited by 68 publications

References 34 publications

Enhanced Mitogenic Signaling in Skeletal Muscle of Women With Polycystic Ovary Syndrome

Enhanced Mitogenic Signaling in Skeletal Muscle of Women With Polycystic Ovary Syndrome

Treatment with TNF-α and IFN-γ alters the activation of SER/THR protein kinases and the metabolic response to IGF-I in mouse c2c12 myogenic cells

Skeletal muscle cells possess a ‘memory’ of acute early life TNF-α exposure: role of epigenetic adaptation

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