TNF-αand IFN-s-Dependent Muscle Decay Is Linked to NF-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi mathvariant="bold-italic">κ</mml:mi></mml:mrow></mml:math>B- and STAT-1α-StimulatedAtrogin1andMuRF1Genes in C2C12 Myotubes

Pijet, Barbara; Pijet, Maja; Litwiniuk, Anna; Gajewska, Małgorzata; Pająk, Beata; Orzechowski, Arkadiusz

doi:10.1155/2013/171437

Cited by 25 publications

(18 citation statements)

References 51 publications

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“…In our previous paper [ 44 ] we showed that cytokine-induced muscle atrophy is mediated by NF-κB and STAT-1α which both cause upregulation of muscle-specific atrogenes (atrogin-1 and MuRF1) that can’t be prevented by insulin. Dehoux et al [ 45 ] also observed that IGF-1 could not overcome the catabolic effect induced by proinflammatory cytokines despite activation of Akt/FOXO and GSK-β pathways and inhibition of atrogin-1 mRNA.…”

Section: Discussionmentioning

confidence: 99%

FOXO1 and GSK-3β Are Main Targets of Insulin-Mediated Myogenesis in C2C12 Muscle Cells

et al. 2016

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Myogenesis and muscle hypertrophy account for muscle growth and adaptation to work overload, respectively. In adults, insulin and insulin-like growth factor 1 stimulate muscle growth, although their links with cellular energy homeostasis are not fully explained. Insulin plays critical role in the control of mitochondrial activity in skeletal muscle cells, and mitochondria are essential for insulin action. The aim of this study was to elucidate molecular mechanism(s) involved in mitochondrial control of insulin-dependent myogenesis. The effects of several metabolic inhibitors (LY294002, PD98059, SB216763, LiCl, rotenone, oligomycin) on the differentiation of C2C12 myoblasts in culture were examined in the short-term (hours) and long-term (days) experiments. Muscle cell viability and mitogenicity were monitored and confronted with the activities of selected genes and proteins expression. These indices focus on the roles of insulin, glycogen synthase kinase 3 beta (GSK-3β) and forkhead box protein O1 (FOXO1) on myogenesis using a combination of treatments and inhibitors. Long-term insulin (10 nM) treatment in “normoglycemic” conditions led to increased myogenin expression and accelerated myogenesis in C2C12 cells. Insulin-dependent myogenesis was accompanied by the rise of mtTFA, MtSSB, Mfn2, and mitochondrially encoded Cox-1 gene expressions and elevated levels of proteins which control functions of mitochondria (kinase—PKB/AKT, mitofusin 2 protein—Mfn-2). Insulin, via the phosphatidylinositol 3-kinase (PI3-K)/AKT-dependent pathway reduced transcription factor FOXO1 activity and altered GSK-3β phosphorylation status. Once FOXO1 and GSK-3β activities were inhibited the rise in Cox-1 gene action and nuclear encoded cytochrome c oxidase subunit IV (COX IV) expressions were observed, even though some mRNA and protein results varied. In contrast to SB216763, LiCl markedly elevated Mfn2 and COX IV protein expression levels when given together with insulin. Thus, inhibition of GSK-3β activity by insulin alone or together with LiCl raised the expression of genes and some proteins central to the metabolic activity of mitochondria resulting in higher ATP synthesis and accelerated myogenesis. The results of this study indicate that there are at least two main targets in insulin-mediated myogenesis: notably FOXO1 and GSK-3β both playing apparent negative role in muscle fiber formation.

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Section: Discussionmentioning

confidence: 99%

FOXO1 and GSK-3β Are Main Targets of Insulin-Mediated Myogenesis in C2C12 Muscle Cells

et al. 2016

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“…In addition, Akt also phosphorylates and inhibits the Forkhead box O (FOXO) family of transcription factors, thereby repressing their transcriptional activation of the E3 ubiquitin ligases Muscle Atrophy Fbox (MAFbx) (also known as atrogin‐1) and Muscle Ring Finger 1 (MuRF1) which function to promote ubiquitination and subsequent proteasomal degradation of target substrates . Pro‐inflammatory cytokines such as tumour necrosis factor alpha (TNF‐α) can also act to induce atrophic genes such as MuRF1 and atrogin‐1/MAFbx by activating the nuclear factor‐kappa B (NF‐kB) family of transcription factors . Therefore, a number of distinct signalling pathways have been implicated in controlling skeletal muscle hypertrophy and atrophy.…”

Section: Introductionmentioning

confidence: 99%

“…9 Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF-α) can also act to induce atrophic genes such as MuRF1 and atrogin-1/MAFbx by activating the nuclear factor-kappa B (NF-kB) family of transcription factors. 26 Therefore, a number of distinct signalling pathways have been implicated in controlling skeletal muscle hypertrophy and atrophy. Notably, diet-induced obesity or short-term high fat feeding has been shown to promote or augment muscle atrophy and catabolism, as evidenced by reduced muscle mass and muscle fibre size, in association with up-regulated expression of atrophic factors (i.e.…”

Section: Introductionmentioning

confidence: 99%

Lipid modulation of skeletal muscle mass and function

Lipina

Hundal

2016

J cachexia sarcopenia muscle

178

156

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Loss of skeletal muscle mass is a characteristic feature of various pathologies including cancer, diabetes, and obesity, as well as being a general feature of ageing. However, the processes underlying its pathogenesis are not fully understood and may involve multiple factors. Importantly, there is growing evidence which supports a role for fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass and function. In this review, we discuss evidence pertaining to those pathways which are involved in the reduction, increase and/or preservation of skeletal muscle mass by such lipids under various pathological conditions, and highlight studies investigating how these processes may be influenced by dietary supplementation as well as genetic and/or pharmacological intervention.

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“…TNF has been reported to trigger muscle catabolism through the NF-κB transcription factor (32), which rapidly enhances the transcription of E3 ubiquitin ligases, such as atrogin-1/MAFbx and MuRF1, and increases the levels of free ubiquitin, which in turn potently mediate the degradation of muscle contractile proteins (23,27,33,34). By contrast, the results of the current study demonstrate that TNF increases VHL expression through a mechanism which is transcriptionindependent, involving the enhanced translation/stabilization of the VHL protein.…”

Section: Discussionmentioning

confidence: 99%

TNF stimulation induces VHL overexpression and impairs angiogenic potential in skeletal muscle myocytes

Basic

Jacobsen

Sirsjö

et al. 2014

International Journal of Molecular Medicine

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Decreased skeletal muscle capillarization is considered to significantly contribute to the development of pulmonary cachexia syndrome (PCS) and progressive muscle wasting in several chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). It is unclear to which extent the concurrent presence of systemic inflammation contributes to decreased skeletal muscle capillarization under these conditions. The present study was designed to examine in vitro the effects of the pro-inflammatory cytokine, tumor necrosis factor (TNF), on the regulation of hypoxia-angiogenesis signal transduction and capillarization in skeletal muscles. For this purpose, fully differentiated C2C12 skeletal muscle myocytes were stimulated with TNF and maintained under normoxic or hypoxic conditions. The expression levels of the putative elements of the hypoxia-angiogenesis signaling cascade were examined using qPCR, western blot analysis and immunofluorescence. Under normoxic conditinos, TNF stimulation increased the protein expression of anti-angiogenic von-Hippel Lindau (VHL), prolyl hydroxylase (PHD)2 and ubiquitin conjugating enzyme 2D1 (Ube2D1), as well as the total ubiquitin content in the skeletal muscle myocytes. By contrast, the expression levels of hypoxia-inducible factor 1‑α (HIF1-α) and those of its transcriptional targets, vascular endothelial growth factor (VEGF)A and glucose transporter 1 (Glut1), were markedly reduced. In addition, hypoxia increased the expression of the VHL transcript and further elevated the VHL protein expression levels in C2C12 myocytes following TNF stimulation. Consequently, an impaired angiogenic potential was observed in the TNF-stimulated myocytes during hypoxia. In conclusion, TNF increases VHL expression and disturbs hypoxia-angiogenesis signal transduction in skeletal muscle myocytes. The current findings provide a mechanism linking systemic inflammation and impaired angiogenesis in skeletal muscle. This is particularly relevant to further understanding the mechanisms mediating muscle wasting and cachexia in patients with chronic inflammatory diseases, such as COPD.

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TNF-αand IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-StimulatedAtrogin1andMuRF1Genes in C2C12 Myotubes

Cited by 25 publications

References 51 publications

FOXO1 and GSK-3β Are Main Targets of Insulin-Mediated Myogenesis in C2C12 Muscle Cells

FOXO1 and GSK-3β Are Main Targets of Insulin-Mediated Myogenesis in C2C12 Muscle Cells

Lipid modulation of skeletal muscle mass and function

TNF stimulation induces VHL overexpression and impairs angiogenic potential in skeletal muscle myocytes

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