Expression of <i>fos</i> and<i>jun</i> genes in human  skeletal muscle after exercise

Puntschart, A; Wey, Eva; Jostarndt, K; Vogt, Michael; Wittwer, Matthias; Widmer, HR; Hoppeler, Hans; Billeter, R.

doi:10.1152/ajpcell.1998.274.1.c129

Cited by 87 publications

(84 citation statements)

References 28 publications

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“…Hypoxia induces transcriptional activation of the canonical AP-1 components c-Fos and c-Jun in vitro (24), as does experimental cerebral ischemia (25) and ischemia in human brain tissue (26). Nonischemic stimuli can trigger AP-1 transcription factor expression, e.g., moderate exercise in human skeletal muscle increases c-Fos, c-Jun, Fra-1, and JunB (27). Similarly, the increased occupancy of the RE-1 site by p53 in ischemic muscle (Fig.…”

Section: Discussionmentioning

confidence: 99%

Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia

Lee

Dahi²,

Mahimkar³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Matrix metalloproteinase-2 (MMP-2) plays an essential role in angiogenesis and arteriogenesis, two processes critical to restoration of tissue perfusion after ischemia. MMP-2 expression is increased in tissue ischemia, but the responsible mechanisms remain unknown. We studied the transcriptional activation of the MMP-2 gene in a model of hindlimb ischemia by using various MMP-2-lacZ reporter mice and chromatin immunoprecipitation. MMP-2 activity and mRNA were increased after hindlimb ischemia. Mice with targeted deletion of MMP-2 had impaired restoration of perfusion and a high incidence of limb gangrene, indicating that MMP-2 plays a critical role in ischemia-induced revascularization. Ischemia induced the expression and binding of c-Fos, c-Jun, JunB, FosB, and Fra2 to a noncanonical activating protein-1 (AP-1) site present in the MMP-2 promoter and decreased binding of the transcriptional repressor JunD. Ischemia also activated the expression and binding of p53 to an adjacent enhancer site (RE-1) and increased expression and binding of nuclear factor of activated T-cells-c2 to consensus sequences within the first intron. Deletion of either the 5 AP-1͞ RE-1 region of the promoter or substitution of the first intron abolished ischemia-induced MMP-2 transcription in vivo. Thus, AP-1 transcription factors and intronic activation by nuclear factor of activated T-cells-c2 act in concert to drive ischemia-induced MMP-2 transcription. These findings define a critical role for MMP-2 in ischemia-induced revascularization and identify both previously uncharacterized regulatory elements within the MMP-2 gene and the cognate transcription factors required for MMP-2 activation in vivo after tissue ischemia.angiogenesis ͉ gelatinase ͉ gene expression ͉ skeletal muscle ͉ transcription factor T issue ischemia secondary to arterial ischemia remains a major source of morbidity and mortality. Despite their importance, the cellular and molecular mechanisms that drive transcription of the genes essential for reversal of ischemia in vivo remain largely undefined. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes important in tissue remodeling and repair. MMP-2 has been implicated in the collateral arterial enlargement that occurs in response to tissue ischemia (1), and its expression is essential for retinal and tumor-induced angiogenesis (2, 3). MMP-2 (gelatinase A) can cleave most extracellular matrix proteins, including collagen, and can proteolytically activate other proenzymes, such as MMP-9. The lack of MMP-14 (membrane-type 1-MMP), the cell surface protease that cleaves proMMP-2 to its active form, abolishes postnatal angiogenesis (4), and targeted deletion of MMP-9 impairs revascularization after hindlimb ischemia (5). Experimental hindlimb ischemia increases expression of MMP-2, MMP-9, and MMP-14 (6). Despite the potential importance of MMP-2 in ischemia-induced angiogenesis and arteriogenesis, the role of MMP-2 in this process and the transcriptional regulatory mechanisms that regulate MMP-2 in tissue is...

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Section: Discussionmentioning

confidence: 99%

Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia

Lee

Dahi²,

Mahimkar³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…The early cellular signals that are associated with contractile activity are known to induce the subsequent expression of mRNAs encoding transcription factors that regulate changes in skeletal muscle phenotype Puntschart et al, 1998). Several studies have demonstrated that changes in the mRNA expression of transcription factors precede the contractile activity-induced regulation of mitochondrial and metabolic plasticity in skeletal muscle (Connor et al, 2001;Irrcher et al, 2003;Michel et al, 1994;Pilegaard et al, 2003;Xia et al, 1997).…”

Section: Gene Expression Response To Contractile Activity and Recoverymentioning

confidence: 99%

“…Several studies have demonstrated that changes in the mRNA expression of transcription factors precede the contractile activity-induced regulation of mitochondrial and metabolic plasticity in skeletal muscle (Connor et al, 2001;Irrcher et al, 2003;Michel et al, 1994;Pilegaard et al, 2003;Xia et al, 1997). These include the induction of a family of immediate early genes (c-fos, c-jun), the early growth response gene-1 (Egr-1), specificity protein 1 (Sp1) and nuclear respiratory factor-1 (NRF-1), which respond to both acute and chronic contractile activity (Abu-Shakra et al, 1993;Connor et al, 2001;Irrcher and Hood, 2004;Michel et al, 1994;Murakami et al, 1998;Neufer et al, 1998;Puntschart et al, 1998;Takahashi et al, 1993). Egr-1 and Sp1 are known to be involved in regulating the transcription of cytochrome c, a nuclear-encoded protein of the electron transport chain (Connor et al, 2001;Freyssenet et al, 2004), while NRF-1 is involved in the transcriptional activation of an even greater diversity of nuclear genes encoding mitochondrial proteins (Kelly and Scarpulla, 2004), including the newly discovered mtDNA transcription factors TFB1M and TFB2M (Gleyzer et al, 2005).…”

Section: Gene Expression Response To Contractile Activity and Recoverymentioning

confidence: 99%

Coordination of metabolic plasticity in skeletal muscle

Hood

Irrcher

Ljubicic

et al. 2006

Journal of Experimental Biology

306

231

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SUMMARY Skeletal muscle is a highly malleable tissue, capable of pronounced metabolic and morphological adaptations in response to contractile activity(i.e. exercise). Each bout of contractile activity results in a coordinated alteration in the expression of a variety of nuclear DNA and mitochondrial DNA(mtDNA) gene products, leading to phenotypic adaptations. This results in an increase in muscle mitochondrial volume and changes in organelle composition,referred to as mitochondrial biogenesis. The functional consequence of this biogenesis is an improved resistance to fatigue. Signals initiated by the exercise bout involve changes in intracellular Ca2+ as well as alterations in energy status (i.e. ATP/ADP ratio) and the consequent activation of downstream kinases such as AMP kinase and Ca2+-calmodulin-activated kinases. These kinases activate transcription factors that bind DNA to affect the transcription of genes, the most evident manifestation of which occurs during the post-exercise recovery period when energy metabolism is directed toward anabolism, rather than contractile activity. An important protein that is affected by exercise is the transcriptional coactivator PGC-1α, which cooperates with multiple transcription factors to induce the expression of nuclear genes encoding mitochondrial proteins. Once translated in the cytosol, these mitochondrially destined proteins are imported into the mitochondrial outer membrane, inner membrane or matrix space via specific import machinery transport components. Contractile activity affects the expression of the import machinery, as well as the kinetics of import, thus facilitating the entry of newly synthesized proteins into the expanding organelle. An important set of proteins that are imported are the mtDNA transcription factors, which influence the expression and replication of mtDNA. While mtDNA contributes only 13 proteins to the synthesis of the organelle, these proteins are vital for the proper assembly of multi-subunit complexes of the respiratory chain,when combined with nuclear-encoded protein subunits. The expansion of skeletal muscle mitochondria during organelle biogenesis involves the assembly of an interconnected network system (i.e. a mitochondrial reticulum). This expansion of membrane size is influenced by the balance between mitochondrial fusion and fission. Thus, mitochondrial biogenesis is an adaptive process that requires the coordination of multiple cellular events, including the transcription of two genomes, the synthesis of lipids and proteins and the stoichiometric assembly of multisubunit protein complexes into a functional respiratory chain. Impairments at any step can lead to defective electron transport, a subsequent failure of ATP production and an inability to maintain energy homeostasis.

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“…The activation of key kinases and mediators within these pathways-importantly, but not exclusively, AMP-activated protein kinase [1,2], Ca 2+ / calmodulin-dependent kinases [3], atypical protein kinase C [4,5], and mitogen-activated protein kinase (MAPK) [6]initiates the upregulation of glucose uptake, which is the acute metabolic effect, and also regulates the adaptive response of the muscle to exercise training. Several of these pathways are involved in the exercise-dependent activation of the transcriptional co-activator peroxisome proliferatoractivated receptor-γ coactivator-1α (PGC-1α) [7,8] and induction of transcription factors nuclear factor-κ light chain gene enhancer in B cells [9], FBJ osteosarcoma oncogene (c-FOS) and the jun oncogene (c-JUN) [10] in the working muscle. The exercise-dependent differential gene expression in the muscle is an important mechanism in the adaptation to regular physical activity.…”

Section: Introductionmentioning

confidence: 99%

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise

et al. 2010

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Aims/hypothesis We aimed to identify, in the liver of mice, signal transduction pathways that show a pronounced regulation by acute exercise. We also aimed to elucidate the role of metabolic stress in this response. Methods C57Bl6 mice performed a 60 min run on a treadmill under non-exhaustive conditions. Hepatic RNA and protein lysates were prepared immediately after running and used for whole-genome-expression analysis, quantitative real-time PCR and immunoblotting. A subset of mice recovered for 3 h after the treadmill run. A further group of mice performed the treadmill run after having received a vitamin C-and vitamin E-enriched diet over 4 weeks. Results The highest number of genes differentially regulated by exercise in the liver was found in the mitogenactivated protein kinase (MAPK) signalling pathway, with a pronounced and transient upregulation of the transcription factors encoded by c-Fos (also known as Fos), c-Jun (also known as Jun), FosB (also known as Fosb) and JunB (also known as Junb) and phosphorylation of hepatic MAPK. Acute exercise also activated the p53 signalling pathway. A major role for oxidative stress is unlikely since the antioxidant-enriched diet did not prevent the activation of the MAPK pathway. In contrast, lower plasma glucose levels after running were related to enhanced levels of MAPK signalling proteins, similar to the upregulation of Igfbp1 and Pgc-1α (also known as Ppargc1a). In the working muscle the activation of the MAPK pathway was weak and not related to plasma glucose concentrations. Conclusions/interpretation Metabolic stress evidenced as low plasma glucose levels appears to be an important determinant for the activation of the MAPK signalling pathway and the transcriptional response of the liver to acute exercise.

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Expression of fos andjun genes in human skeletal muscle after exercise

Cited by 87 publications

References 28 publications

Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia

Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia

Coordination of metabolic plasticity in skeletal muscle

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise

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