Regulation of skeletal muscle gene expression by p38 MAP kinases

Lluı́s, Frederic; Perdiguero, Eusebio; Nebreda, Ángel R.; Muñoz‐Cánoves, Pura

doi:10.1016/j.tcb.2005.11.002

Cited by 253 publications

(255 citation statements)

References 63 publications

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“…The exercise-induced increase in MyoD during the late and terminal steps of differentiation is consistent with the increased expression of muscle-specific genes and the fast recovery of muscle mass shown in exercised animals. Moreover, specific ERK1/2 and p38 MAPKs have been shown to have an important role in the proliferation and early differenciation in cultured cells (33,35). We showed in the present study that the early steps of muscle regeneration were associated with high levels of phosphorylated ERK1/2, which returned to basal values on day 14.…”

Section: Discussionsupporting

confidence: 63%

“…Myogenesis is a dynamic process controlled by members of MRFs, in association with specific transcription cofactors such as members of the MEF2 family (33). Although it could be expected that MyoD and myogenin peaked earlier, the present experiments show that both MRFs were still increased in Reg muscles 5 days after muscle injury, with further elevated levels under running conditions on days 14 and 21 for MyoD and myogenin, respectively.…”

Section: Discussioncontrasting

confidence: 57%

“…Surprisingly, ERK1/2 protein levels were lower in Act rats than in Sed rats on day 5, but the increased levels of this activated MAPK observed 21 days after muscle injury could favor the late steps of muscle differentiation through motor nerve activity (36). Although p38 MAPK activity plays an essential role in muscle differentiation (33), p38 phosphorylation in Act rats had returned to levels reported in Int-Sed muscles on day 14. This finding is surprising and not consistent with the positive effects of exercise on muscle mass recovery.…”

Section: Discussionmentioning

confidence: 83%

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Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity

Richard-Bulteau¹,

Serrurier²,

Crassous³

et al. 2008

American Journal of Physiology-Cell Physiology

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Section: Discussionsupporting

confidence: 63%

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 83%

See 1 more Smart Citation

Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity

Richard-Bulteau¹,

Serrurier²,

Crassous³

et al. 2008

American Journal of Physiology-Cell Physiology

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“…Given MEF2A transcriptional autoregulation, it is not surprising that we observed sensitivity of MEF2A transcription and steadystate mRNA abundance to p38 signaling. Because p38 activity both stimulates and is required for myogenesis (7,66,(71)(72)(73)(74), MAPK-mediated stimulation of MEF2A autoregulation is likely to be involved. MEF2 factors can tether to DNA-bound bHLH factors at E boxes (53) and to Sp1 at GC boxes (49).…”

Section: Discussionmentioning

confidence: 99%

Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated

Ramachandran

et al. 2008

Journal of Biological Chemistry

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MEF2 (myocyte enhancer factor 2) proteins are a small family of transcription factors that play pivotal roles in striated muscle differentiation, development, and metabolism, in neuron survival and synaptic formation, and in lymphocyte selection and activation. Products of the four mammalian MEF2 genes, MEF2A, MEF2B, MEF2C, and MEF2D, are expressed with overlapping but distinct temporospatial patterns. Toward analysis of MEF2A functions and the determinants of its regulated expression, we have mapped and begun studies of the transcriptional control regions of this gene. Heterogeneous 5 -untranslated regions of MEF2A mRNAs result from use of alternative promoters and splicing patterns. The two closely approximated TATA-less promoters are ϳ65 kb upstream of the exon containing the sole initiation codon. Ribonuclease protection and primer extension assays show that each promoter is active in various adult tissues. A canonical MEF2 site overlies the major promoter 1 transcription start site. This element specifically binds MEF2 factors, including endogenous nuclear MEF2A according to chromatin immunoprecipitation studies, and is critical to MEF2A transcription in myocytes. The site exerts reciprocal control of the alternative promoters, silencing promoter 1 and activating promoter 2 under some conditions. Erk5 and p38 MAPK signaling stimulate MEF2A expression by activating both promoters from the MEF2 element. MEF2A transcription is therefore subject to positive or negative regulation by its protein products, depending on signaling activities that influence MEF2 factor trans-activity. The sole MEF2 gene of the cephalochordate amphioxus has a similar regulatory region structure, suggesting that this mode of autoregulatory control is conserved among higher metazoan MEF2 genes.

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“…Here, we also confirm this E2 effect in differentiating conditions. In fact, E2, like IGF-I, rapidly increases both the activation of AKT, linked to muscle development, regeneration, and hypertrophy (Lawlor and Rotwein 2000;Rommel et al 2001;Sandri et al 2004) and the p38/MAPK signaling pathway, which is crucial for the transcriptional control of skeletal muscle differentiation and for the fusion of myoblasts into myotubes (Lluis et al 2006). Although several studies suggest that the two pathways are parallel (Keren et al 2006), present data demonstrate that p38 MAPK activation is not sufficient to enhance myoblast differentiation, highlighting the pivotal role of ERa-activated AKT in promoting E2-mediated myoblast differentiation.…”

Section: Discussionmentioning

confidence: 99%

Naringenin modulates skeletal muscle differentiation via estrogen receptor α and β signal pathway regulation

et al. 2014

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Several experiments sustain healthful benefits of the flavanone naringenin (Nar) against chronic diseases including its protective effects against estrogen-related cancers. These experiments encourage Nar use in replacing estrogen treatment in post-menopausal women avoiding the serious side effects ascribed to this hormone. However, at the present, scarce data are available on the impact of Nar on E2-regulated cell functions. This study was aimed at determining the impact of Nar on the estrogen receptor (ERa and b)-dependent signals important for 17b-estradiol (E2) effect in muscle cells (rat L6 myoblasts, mouse C2C12 myoblasts, and mouse skeletal muscle satellite cells). Dietary relevant concentration of Nar delays the appearance of skeletal muscle differentiation markers (i.e., GLUT4 translocation, myogenin, and both fetal and slow MHC isoforms) and impairs E2 effects specifically hampering ERa ability to activate AKT. Intriguingly, Nar effects are specific for E2-initiating signals because IGF-Iinduced AKT activation, and myoblast differentiation markers were not affected by Nar treatment. Only 7 days after Nar stimulation, early myoblast differentiation markers (i.e., myogenin, and fetal MHC) start to be accumulated in myoblasts. On the other hand, Nar stimulation activates, via ERb, the phosphorylation of p38/MAPK involved in reducing the reactive oxygen species formation in skeletal muscle cells. As a whole, data reported here strongly sustain that although Nar action mechanisms include the impairment of ERa signals which drive muscle cells to differentiation, the effects triggered by Nar in the presence of ERb could balance this negative effect avoiding the toxic effects produced by oxidative stress.

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Regulation of skeletal muscle gene expression by p38 MAP kinases

Cited by 253 publications

References 63 publications

Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity

Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity

Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated

Naringenin modulates skeletal muscle differentiation via estrogen receptor α and β signal pathway regulation

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