+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Exercise activation of muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling is redox sensitive

Exercise activation of muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling is redox sensitive

Free Radical Biology and Medicine 47(10): 1394-1400

The peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)-activated signal transduction pathway has previously been shown to stimulate mitochondrial biogenesis in skeletal muscle in response to endurance exercise. In vitro data indicate that PGC-1alpha signaling may be sensitive to reactive oxygen species (ROS) but its role in vivo is not clear. The objectives of this study were (1) to investigate whether the PGC-1alpha pathway could be activated by a single bout of anaerobic exercise in rats, wherein a major portion of ROS was generated via the cytosolic xanthine oxidase (XO), and (2) to examine whether allopurinol (ALP), a specific XO inhibitor, would attenuate PGC-1alpha expression and signaling owing to decreased ROS generation. Female Sprague-Dawley rats were randomly divided into three groups: (1) subjected to sprinting on a treadmill at 35 m/min, 15% grade, for 3 min followed by 3 min slow running at 15 m/min, 0% grade, repeated until exhaustion (88 +/- 4 min; Exer; N= 9); (2) subjected to the same exercise protocol (88 +/- 4 min) but injected with two doses of ALP (0.4 mmol/kg, ip) 24 and 1 h before the experiment (Exer+ ALP; N= 9); and (3) rested control (C; N= 9). Exercise increased XO activity and ROS generation in the Exer rat vastus lateralis muscle (P< 0.05), whereas the Exer+ ALP group displayed only 7% XO activity and similar ROS level compared with the C group. PGC-1alpha protein content showed a 5.6-fold increase (P< 0.01) in Exer vs C, along with a 200% (P< 0.01) increase in both nuclear respiratory factor (NRF)-1 and mitochondrial transcription factor A (Tfam) content. ALP treatment decreased PGC-1alpha, NRF-1, and Tfam levels by 45, 19, and 20% (P< 0.05), respectively. Exercise doubled the content of the phosphorylated cAMP-responsive element-binding protein in the Exer group (P< 0.01) and tripled phosphorylated p38 mitogen-activated protein kinase (P< 0.01), whereas these effects were reduced by 60 and 30% (P< 0.01, P< 0.05), respectively, in Exer+ ALP rats. Nuclear factor-kappaB binding and phospho-IkappaB content were also increased in Exer rats (P< 0.01) and these increases were abolished by ALP treatment. The data indicate that contraction-activated PGC-1alpha signaling pathways in skeletal muscle are redox sensitive and that nonmitochondrial ROS play an important role in stimulating mitochondrial biogenesis.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053116583

Download citation: RISBibTeXText

PMID: 19686839

DOI: 10.1016/j.freeradbiomed.2009.08.007

Related references

An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation. Endocrinology 148(7): 3441-3448, 2007

Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. Endocrinology 149(9): 4527-4533, 2008

Activation of peroxisome proliferator-activated receptor beta/delta induces lung cancer growth via peroxisome proliferator-activated receptor coactivator gamma-1alpha. American Journal of Respiratory Cell and Molecular Biology 40(3): 325-331, 2008

Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1alpha gene transcription: an autoregulatory loop controls PGC-1alpha expression in adipocytes via peroxisome proliferator-activated receptor-gamma coactivation. Endocrinology 147(6): 2829-2838, 2006

p38 mitogen-activated protein kinase and calcium channels mediate signaling in depolarization-induced activation of peroxisome proliferator-activated receptor gamma coactivator-1alpha in neurons. Journal of Neuroscience Research 88(3): 640-649, 2010

Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha protein expressions in rat skeletal muscle. Metabolism: Clinical and Experimental 57(7): 986-998, 2008

Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes & Development 18(2): 157-169, 2004

alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice. Metabolism: Clinical and Experimental 59(7): 967-976, 2010

Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise. Journal of Biological Chemistry 286(35): 30561-30570, 2011

Palmitate-mediated downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha in skeletal muscle cells involves MEK1/2 and nuclear factor-kappaB activation. Diabetes 55(10): 2779-2787, 2006

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) stimulates VLDL assembly through activation of cell death-inducing DFFA-like effector B (CideB). Journal of Biological Chemistry 285(34): 25996-26004, 2010

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha in muscle links metabolism to inflammation. Clinical and Experimental Pharmacology and Physiology 36(12): 1139-1143, 2010

Impaired coactivator activity of the Gly482 variant of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) on mitochondrial transcription factor A (Tfam) promoter. Biochemical and Biophysical Research Communications 344(3): 708-712, 2006

An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proceedings of the National Academy of Sciences of the United States of America 100(12): 7111-7116, 2003

Calcium induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation. Journal of Biological Chemistry 282(26): 18793-9, 2007