Document Detail

Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle.
MedLine Citation:
PMID:  15878932     Owner:  NLM     Status:  MEDLINE    
We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body alpha2- and alpha1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmill running (90 min), and in recovery. Running increased alpha1-AMPK kinase activity, phosphorylation (P) of AMPK, and acetyl-CoA carboxylase (ACC)beta in alpha2-WT and alpha2-KO muscles and increased alpha2-AMPK kinase activity in alpha2-WT. In alpha2-KO muscles, AMPK-P and ACCbeta-P were markedly lower compared with alpha2-WT. However, in alpha1-WT and alpha1-KO muscles, AMPK-P and ACCbeta-P levels were identical at rest and increased similarly during exercise in the two genotypes. The alpha2-KO decreased peroxisome-proliferator-activated receptor gamma coactivator (PGC)-1alpha, uncoupling protein-3 (UCP3), and hexokinase II (HKII) transcription at rest but did not affect exercise-induced transcription. Exercise increased the mRNA content of PGC-1alpha, Forkhead box class O (FOXO)1, HKII, and pyruvate dehydrogenase kinase 4 (PDK4) similarly in alpha2-WT and alpha2-KO mice, whereas glucose transporter GLUT 4, carnitine palmitoyltransferase 1 (CPTI), lipoprotein lipase, and UCP3 mRNA were unchanged by exercise in both genotypes. CPTI mRNA was lower in alpha2-KO muscles than in alpha2-WT muscles at all time-points. In alpha1-WT and alpha1-KO muscles, running increased the mRNA content of PGC-1alpha and FOXO1 similarly. The alpha2-KO was associated with lower muscle adenosine 5'-triphosphate content, and the inosine monophosphate content increased substantially at the end of exercise only in alpha2-KO muscles. In addition, subcutaneous injection of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) increased the mRNA content of PGC-1alpha, HKII, FOXO1, PDK4, and UCP3, and alpha2-KO abolished the AICAR-induced increases in PGC-1alpha and HKII mRNA. In conclusion, KO of the alpha2- but not the alpha1-AMPK isoform markedly diminished AMPK activation during running. Nevertheless, exercise-induced activation of the investigated genes in mouse skeletal muscle was not impaired in alpha1- or alpha2-AMPK KO muscles. Although it cannot be ruled out that activation of the remaining alpha-isoform is sufficient to increase gene activation during exercise, the present data do not support an essential role of AMPK in regulating exercise-induced gene activation in skeletal muscle.
Sebastian B Jørgensen; Jørgen F P Wojtaszewski; Benoit Viollet; Fabrizio Andreelli; Jesper B Birk; Ylva Hellsten; Peter Schjerling; Sophie Vaulont; P Darrell Neufer; Erik A Richter; Henriette Pilegaard
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-05-05
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  19     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-29     Completed Date:  2006-02-23     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1146-8     Citation Subset:  IM    
Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark.
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MeSH Terms
AMP-Activated Protein Kinases
Acetyl-CoA Carboxylase / analysis
Adenosine Monophosphate / analysis
Adenosine Triphosphate / analysis
Aminoimidazole Carboxamide / analogs & derivatives,  pharmacology
Carrier Proteins / genetics
Gene Expression Regulation*
Glycogen / analysis
Hexokinase / genetics
Inosine Monophosphate / analysis
Ion Channels
Mice, Knockout
Mitochondrial Proteins
Multienzyme Complexes / analysis,  metabolism,  physiology*
Muscle, Skeletal / metabolism*
Physical Conditioning, Animal*
Protein Kinases / genetics
Protein-Serine-Threonine Kinases / analysis,  metabolism,  physiology*
RNA, Messenger / analysis
Ribonucleotides / pharmacology
Trans-Activators / genetics
Transcription, Genetic
Transcriptional Activation
Reg. No./Substance:
0/Carrier Proteins; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Multienzyme Complexes; 0/Ppargc1a protein, mouse; 0/RNA, Messenger; 0/Ribonucleotides; 0/Trans-Activators; 0/mitochondrial uncoupling protein 3; 131-99-7/Inosine Monophosphate; 3031-94-5/AICA ribonucleotide; 360-97-4/Aminoimidazole Carboxamide; 56-65-5/Adenosine Triphosphate; 61-19-8/Adenosine Monophosphate; 9005-79-2/Glycogen; EC 2.7.-/Protein Kinases; EC 2.7.1.-/pyruvate dehydrogenase kinase 4; EC; EC Protein Kinases; EC Kinases; EC Carboxylase

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