Acute endurance exercise increases the nuclear abundance of PGC-1alpha in trained human skeletal muscle.
Peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) is a transcriptional coactivator that plays a key role in coordinating mitochondrial biogenesis. Recent evidence has linked p38 MAPK and AMPK with activation of PGC-1alpha. It was recently shown in rodent skeletal muscle that acute endurance exercise causes a shift in the subcellular localization of PGC-1alpha from the cytosol to the nucleus, allowing PGC-1alpha to coactivate transcription factors and increase mitochondrial gene expression, but human data are limited and equivocal in this regard. Our purpose was to examine p38 MAPK and AMPK activation, and PGC-1alpha protein content in whole muscle, cytosolic, and nuclear fractions of human skeletal muscle following an acute bout of endurance exercise. Eight trained men (29 +/- 3 yr; Vo(2peak) = 55 +/- 2 ml.kg(-1).min(-1)) cycled for 90 min at approximately 65% of Vo(2peak) and needle biopsy samples (vastus lateralis) were obtained before and immediately after exercise. At rest, the majority of PGC-1alpha was detected in cytosolic compared with the nuclear fractions. In response to exercise, nuclear PGC-1alpha protein increased by 54% (P < 0.05), yet whole muscle PGC-1alpha protein was unchanged compared with rest. Whole muscle and cytosolic p38 MAPK phosphorylation increased several-fold immediately after exercise compared with rest (P < 0.05). Acetyl CoA carboxylase (ACC) phosphorylation, a marker of AMPK activation, was increased by approximately 5-fold in cytosolic fractions following exercise (P < 0.05). These data provide evidence that, in human skeletal muscle, activation of cytosolic p38 MAPK and AMPK may be potential signals that lead to increased nuclear abundance and activation of PGC-1alpha in response to an acute bout of endurance exercise.
Little
Jonathan P
JP
Department of Kinesiology, McMaster University, Ivor Wynne Centre, Hamilton, ON L8S 4K1.
Safdar
Adeel
A
Cermak
Naomi
N
Tarnopolsky
Mark A
MA
Gibala
Martin J
MJ
D000263:Adenylate Kinase / Q000378:metabolism; D000328:Adult; D056352:Athletes; D002467:Cell Nucleus / Q000201:enzymology / Q000502:physiology*; D003600:Cytosol / Q000201:enzymology / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D010807:Physical Endurance / Q000502:physiology*; D012016:Reference Values; D012146:Rest / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase