Regulation of Egr-1, SRF, and Sp1 mRNA expression in contracting skeletal muscle cells.

The early cellular signals associated with contractile activity initiate the activation and induction of transcription factors that regulate changes in skeletal muscle phenotype. The transcription factors Egr-1, Sp1, and serum response factor (SRF) are potentially important mediators of mitochondrial biogenesis based on the prevalence of binding sites for them in the promoter regions of genes encoding mitochondrial proteins, including PGC-1 alpha, the important regulator of mitochondrial biogenesis. Thus, to further define a role for transcription factors at the onset of contractile activity, we examined the time-dependent alterations in Egr-1, Sp1, and SRF mRNA and the levels in electrically stimulated mouse C(2)C(12) skeletal muscle cells. Early transient increases in Egr-1 mRNA levels within 30 min (P < 0.05) of contractile activity led to threefold increases (P < 0.05) in Egr-1 protein by 60 min. The increase in Egr-1 mRNA was not because of increased stability, as Egr-1 mRNA half-life after 30 min of stimulation showed only a 58% decline. Stimulation of muscle cells had no effect on Sp1 mRNA but led to progressive increases (P < 0.05) in SRF mRNA by 30 and 60 min. This was not matched by increases in SRF protein but occurred coincident with increases (P < 0.05) in SRF-serum response element DNA binding at 30 and 60 min as a result of SRF phosphorylation on serine-103. To assess the importance of the recovery period, 12 h of continuous contractile activity was compared with four successive 3-h bouts, with an intervening 21-h recovery period after each bout. Continuous contractile activity led to a twofold increase (P < 0.05) in Egr-1 mRNA, no change in SRF mRNA, and a 43% decrease in Sp1 mRNA expression. The recovery period prevented the decline in Sp1 mRNA, produced a decrease in Egr-1 mRNA, and had no effect on SRF mRNA. Thus continuous and intermittent contractile activity evoked different specific transcription factor expression patterns, which may ultimately contribute to divergent qualitative, or temporal patterns of, phenotypic adaptation in muscle.

[1]  D. Freyssenet,et al.  Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells. , 2004, American journal of physiology. Cell physiology.

[2]  B. Robinson,et al.  Compensatory responses of protein import and transcription factor expression in mitochondrial DNA defects. , 2004, American journal of physiology. Cell physiology.

[3]  R. Scarpulla,et al.  Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. , 2004, Genes & development.

[4]  D. Hood,et al.  PPARγ coactivator-1α expression during thyroid hormone-and contractile activity-induced mitochondrial adaptations , 2003 .

[5]  Henriette Pilegaard,et al.  Exercise induces transient transcriptional activation of the PGC‐1α gene in human skeletal muscle , 2003, The Journal of physiology.

[6]  G. Shulman,et al.  AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Bassel-Duby,et al.  Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK , 2002, Science.

[8]  M. Lafage-Proust,et al.  MAPK and SRC-kinases control EGR-1 and NF-kappa B inductions by changes in mechanical environment in osteoblasts. , 2001, Biochemical and biophysical research communications.

[9]  M. Connor,et al.  Contractile Activity-induced Transcriptional Activation of Cytochrome c Involves Sp1 and Is Proportional to Mitochondrial ATP Synthesis in C2C12 Muscle Cells* , 2001, The Journal of Biological Chemistry.

[10]  D. Hood.  Plasticity in Skeletal, Cardiac, and Smooth Muscle Invited Review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle , 2001 .

[11]  S. Gordon,et al.  Selected Contribution: Skeletal muscle focal adhesion kinase, paxillin, and serum response factor are loading dependent. , 2001, Journal of applied physiology.

[12]  P. Neufer,et al.  Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise. , 2000, American journal of physiology. Endocrinology and metabolism.

[13]  M. Permutt,et al.  Activation of Serum Response Factor in the Depolarization Induction of Egr-1 Transcription in Pancreatic Islet β-Cells* , 2000, The Journal of Biological Chemistry.

[14]  M. Waxham,et al.  Skeletal muscle CaMKII enriches in nuclei and phosphorylates myogenic factor SRF at multiple sites. , 2000, Biochemical and biophysical research communications.

[15]  M. Waxham,et al.  Skeletal muscle Ca(2+)-independent kinase activity increases during either hypertrophy or running. , 2000, Journal of applied physiology.

[16]  H. Esterbauer,et al.  Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. , 1999, Genomics.

[17]  R. Schwartz,et al.  SRF protein is upregulated during stretch-induced hypertrophy of rooster ALD muscle. , 1999, Journal of applied physiology.

[18]  V. Sukhatme,et al.  Rapid induction and translocation of Egr-1 in response to mechanical strain in vascular smooth muscle cells. , 1999, Circulation research.

[19]  A. Zaid,et al.  On the Role of the General Transcription Factor Sp1 in the Activation and Repression of Diverse Mammalian Oxidative Phosphorylation Genes* , 1999, Journal of bioenergetics and biomembranes.

[20]  J. Merchant,et al.  Sp1 phosphorylation by Erk 2 stimulates DNA binding. , 1999, Biochemical and biophysical research communications.

[21]  F. Booth,et al.  Effect of serum and mechanical stretch on skeletal α-actin gene regulation in cultured primary muscle cells. , 1998, American journal of physiology. Cell physiology.

[22]  M. Sokabe,et al.  Induction of nuclear respiratory factor-1 expression by an acute bout of exercise in rat muscle. , 1998, Biochimica et biophysica acta.

[23]  P. Neufer,et al.  Transient regulation of c-fos, alpha B-crystallin, and hsp70 in muscle during recovery from contractile activity. , 1998, The American journal of physiology.

[24]  N. Lenka,et al.  Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. , 1998, Progress in nucleic acid research and molecular biology.

[25]  R. Billeter,et al.  Expression of fos and jun genes in human skeletal muscle after exercise. , 1998, The American journal of physiology.

[26]  R. Scarpulla,et al.  Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R J Schwartz,et al.  Organization and Myogenic Restricted Expression of the Murine Serum Response Factor Gene , 1997, The Journal of Biological Chemistry.

[28]  R. Scarpulla.  Nuclear Control of Respiratory Chain Expression in Mammalian Cells , 1997, Journal of bioenergetics and biomembranes.

[29]  M. Connor,et al.  Tissue-specific stability of nuclear- and mitochondrially encoded mRNAs. , 1996, Archives of biochemistry and biophysics.

[30]  R. Misra,et al.  Expression of the Serum Response Factor Gene Is Regulated by Serum Response Factor Binding Sites* , 1996, The Journal of Biological Chemistry.

[31]  M. Greenberg,et al.  Calcium activates serum response factor-dependent transcription by a Ras- and Elk-1-independent mechanism that involves a Ca2+/calmodulin-dependent kinase , 1995, Molecular and cellular biology.

[32]  R. Li,et al.  The role of thyroid hormone and promoter diversity in the regulation of nuclear encoded mitochondrial proteins. , 1995, Biochimica et biophysica acta.

[33]  A. Cole,et al.  Cholinergic stimulation of skeletal muscle cells induces rapid immediate early gene expression: role of intracellular calcium. , 1994, Brain research. Molecular brain research.

[34]  J. Richardson,et al.  Biphasic induction of immediate early gene expression accompanies activity-dependent angiogenesis and myofiber remodeling of rabbit skeletal muscle. , 1994, The Journal of clinical investigation.

[35]  M. Greenberg,et al.  A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity , 1993, Molecular and cellular biology.

[36]  A. Cole,et al.  Nerve stimulation and denervation induce differential patterns of immediate early gene mRNA expression in skeletal muscle. , 1993, Brain research. Molecular brain research.

[37]  D. Hood,et al.  delta-Aminolaevulinate synthase expression in muscle after contractions and recovery. , 1993, The Biochemical journal.

[38]  A. Moorman,et al.  Isolation and characterization of the rat gene encoding glutamate dehydrogenase. , 1993, European journal of biochemistry.

[39]  P. Worley,et al.  Regulation of immediate early genes in brain: role of NMDA receptor activation. , 1990, Progress in brain research.

[40]  D. Nathans,et al.  Functional serum response elements upstream of the growth factor-inducible gene zif268 , 1989, Molecular and cellular biology.

[41]  D. Pette,et al.  Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome-c-oxidase subunits. , 1989, European journal of biochemistry.

[42]  V. Sukhatme,et al.  5' flanking sequence and genomic structure of Egr-1, a murine mitogen inducible zinc finger encoding gene. , 1988, Nucleic acids research.

[43]  S. Salmons,et al.  Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle. , 1986, The Journal of biological chemistry.