Originally published In Press as doi:10.1074/jbc.M408862200 on March 14, 2005
J. Biol. Chem., Vol. 280, Issue 20, 19587-19593, May 20, 2005
Exercise Stimulates Pgc-1
Transcription in Skeletal Muscle through Activation of the p38 MAPK Pathway*
Takayuki Akimoto
,
Steven C. Pohnert,
Ping Li,
Mei Zhang,
Curtis Gumbs,
Paul B. Rosenberg,
R. Sanders Williams, and
Zhen Yan¶
From the
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710
Peroxisome proliferator-activated receptor 
co-activator 1
(PGC-1) promotes mitochondrial biogenesis and slow fiber formation in skeletal muscle. We hypothesized that activation of the p38 mitogen-activated protein kinase (MAPK) pathway in response to increased muscle activity stimulated Pgc-1 gene transcription as part of the mechanisms for skeletal muscle adaptation. Here we report that a single bout of voluntary running induced a transient increase of Pgc-1 mRNA expression in mouse plantaris muscle, concurrent with an activation of the p38 MAPK pathway. Activation of the p38 MAPK pathway in cultured C2C12 myocytes stimulated Pgc-1 promoter activity, which could be blocked by the specific inhibitors of p38, SB203580 and SB202190, or a dominant negative p38. Furthermore, the p38-mediated increase in Pgc-1 promoter activity was enhanced by increased expression of the downstream transcription factor ATF2 and completely blocked by ATF2
N, a dominant negative ATF2. Skeletal muscle-specific expression of a constitutively active activator of p38, MKK6E, in transgenic mice resulted in enhanced Pgc-1 and cytochrome oxidase IV protein expression in fast-twitch skeletal muscles. These findings suggest that contractile activity-induced activation of the p38 MAPK pathway promotes Pgc-1 gene expression and skeletal muscle adaptation.
Received for publication, August 3, 2004
, and in revised form, March 11, 2005.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Both authors contributed equally to this work.
Recipient of a grant-in-aid for overseas research scholars from the Ministry of Education, Science, and Culture of Japan.
¶ To whom correspondence should be addressed: Division of Cardiology, Dept. of Medicine, Duke University Medical Center, 4321 Medical Park Dr., Suite 200, Durham, NC 27704. Tel.: 919-479-2373; Fax: 919-477-0632; E-mail: zhen.yan{at}duke.edu.
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|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
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|
|
|
|
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|
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|
|
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|
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|
|
|
|
|
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104(1):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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583(2):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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56(8):
2062 - 2069.
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[PDF]
|
|
|
|
|
|
|
H. F. Kramer and L. J. Goodyear
Exercise, MAPK, and NF-{kappa}B signaling in skeletal muscle
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July 1, 2007;
103(1):
388 - 395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Miura, K. Kawanaka, Y. Kai, M. Tamura, M. Goto, T. Shiuchi, Y. Minokoshi, and O. Ezaki
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July 1, 2007;
148(7):
3441 - 3448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Wright, P. C. Geiger, D.-H. Han, T. E. Jones, and J. O. Holloszy
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J. Biol. Chem.,
June 29, 2007;
282(26):
18793 - 18799.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Crunkhorn, F. Dearie, C. Mantzoros, H. Gami, W. S. da Silva, D. Espinoza, R. Faucette, K. Barry, A. C. Bianco, and M. E. Patti
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May 25, 2007;
282(21):
15439 - 15450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Xiong, Q. F. Collins, J. An, E. Lupo Jr., H.-Y. Liu, D. Liu, J. Robidoux, Z. Liu, and W. Cao
p38 Mitogen-activated Protein Kinase Plays an Inhibitory Role in Hepatic Lipogenesis
J. Biol. Chem.,
February 16, 2007;
282(7):
4975 - 4982.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Rasbach and R. G. Schnellmann
Signaling of Mitochondrial Biogenesis following Oxidant Injury
J. Biol. Chem.,
January 26, 2007;
282(4):
2355 - 2362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Wright, D.-H. Han, P. M. Garcia-Roves, P. C. Geiger, T. E. Jones, and J. O. Holloszy
Exercise-induced Mitochondrial Biogenesis Begins before the Increase in Muscle PGC-1{alpha} Expression
J. Biol. Chem.,
January 5, 2007;
282(1):
194 - 199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Ventura-Clapier, B. Mettauer, and X. Bigard
Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure
Cardiovasc Res,
January 1, 2007;
73(1):
10 - 18.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Liang and W. F. Ward
PGC-1{alpha}: a key regulator of energy metabolism
Advan Physiol Educ,
December 1, 2006;
30(4):
145 - 151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Russ and R. M. Lovering
Influence of activation frequency on cellular signalling pathways during fatiguing contractions in rat skeletal muscle
Exp Physiol,
November 1, 2006;
91(6):
957 - 966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Wu, X. Huang, Y. Feng, C. Handschin, Y. Feng, P. S. Gullicksen, O. Bare, M. Labow, B. Spiegelman, and S. C. Stevenson
Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1{alpha} transcription and mitochondrial biogenesis in muscle cells
PNAS,
September 26, 2006;
103(39):
14379 - 14384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. F. Collins, Y. Xiong, E. G. Lupo Jr., H.-Y. Liu, and W. Cao
p38 Mitogen-activated Protein Kinase Mediates Free Fatty Acid-induced Gluconeogenesis in Hepatocytes
J. Biol. Chem.,
August 25, 2006;
281(34):
24336 - 24344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Hood, I. Irrcher, V. Ljubicic, and A.-M. Joseph
Coordination of metabolic plasticity in skeletal muscle
J. Exp. Biol.,
June 15, 2006;
209(12):
2265 - 2275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Li, T. Akimoto, M. Zhang, R. S. Williams, and Z. Yan
Resident stem cells are not required for exercise-induced fiber-type switching and angiogenesis but are necessary for activity-dependent muscle growth
Am J Physiol Cell Physiol,
June 1, 2006;
290(6):
C1461 - C1468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Benton, X.-X. Han, M. Febbraio, T. E. Graham, and A. Bonen
Inverse relationship between PGC-1{alpha} protein expression and triacylglycerol accumulation in rodent skeletal muscle
J Appl Physiol,
February 1, 2006;
100(2):
377 - 383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Choi, X. Liu, P. Li, T. Akimoto, S. Y. Lee, M. Zhang, and Z. Yan
Transcriptional profiling in mouse skeletal muscle following a single bout of voluntary running: evidence of increased cell proliferation
J Appl Physiol,
December 1, 2005;
99(6):
2406 - 2415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Corton and H. M. Brown-Borg
Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1 in Caloric Restriction and Other Models of Longevity
J. Gerontol. A Biol. Sci. Med. Sci.,
December 1, 2005;
60(12):
1494 - 1509.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. B. Taylor, J. D. Lamb, R. W. Hurst, D. G. Chesser, W. J. Ellingson, L. J. Greenwood, B. B. Porter, S. T. Herway, and W. W. Winder
Endurance training increases skeletal muscle LKB1 and PGC-1{alpha} protein abundance: effects of time and intensity
Am J Physiol Endocrinol Metab,
December 1, 2005;
289(6):
E960 - E968.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. R. Koves, P. Li, J. An, T. Akimoto, D. Slentz, O. Ilkayeva, G. L. Dohm, Z. Yan, C. B. Newgard, and D. M. Muoio
Peroxisome Proliferator-activated Receptor-{gamma} Co-activator 1{alpha}-mediated Metabolic Remodeling of Skeletal Myocytes Mimics Exercise Training and Reverses Lipid-induced Mitochondrial Inefficiency
J. Biol. Chem.,
September 30, 2005;
280(39):
33588 - 33598.
[Abstract]
[Full Text]
[PDF]
|
|
|
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