title: Effect of exercise intensity and AICAR on isoform-specific expressions of murine skeletal muscle PGC-1α mRNA: a role of β₂-adrenergic receptor activation.
abstract: There are three isoforms of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) mRNA, which promotes mitochondrial biogenesis in skeletal muscles. Compared with PGC-1α-a mRNA, PGC-1α-b or PGC-1α-c mRNA is transcribed by a different exon 1 of the PGC-1α gene. In this study, effects of exercise intensity and 5-aminoimidazole-4-carboxamide-1β-d-ribofuranoside (AICAR) on isoform-specific expressions of PGC-1α were investigated. All isoforms were increased in proportion to exercise intensity of treadmill running (10-30 m/min for 30 min). Preinjection of β₂-adrenergic receptor (AR) antagonist (ICI 118551) inhibited the increase in PGC-1α-b and PGC-1α-c mRNAs, but not the increase in PGC-1α-a mRNA, in response to high-intensity exercise. Although high-intensity exercise activated α2-AMP-activated protein kinase (α2-AMPK) in skeletal muscles, inactivation of α2-AMPK activity did not affect high-intensity exercise-induced mRNA expression of all PGC-1α isoforms, suggesting that activation of α2-AMPK is not mandatory for an increase in PGC-1α mRNA by high-intensity exercise. A single injection in mice of AICAR, an AMPK activator, increased mRNAs of all PGC-1α isoforms. AICAR increased blood catecholamine concentrations, and preinjection of β₂-AR antagonist inhibited the increase in PGC-1α-b and PGC-1α-c mRNAs but not the increase in PGC-1α-a mRNA. Direct exposure of epitrochlearis muscle to AICAR increased PGC-1α-a but not the -b isoform. These data indicate that exercise-induced PGC-1α expression was dependent on the intensity of exercise. Exercise or AICAR injection increased PGC-1α-b and PGC-1α-c mRNAs via β₂-AR activation, whereas high-intensity exercise increased PGC-1α-a expression by a multiple mechanism in which α2-AMPK is one of the signaling pathways.
authors.affiliation: National Institute of Health and Nutrition, Tokyo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tadaishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kai
authors.forename: Emi
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koshinaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kawanaka
authors.forename: Junichi
authors.initials: J
authors.lastname: Nagata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oishi
authors.forename: Osamu
authors.initials: O
authors.lastname: Ezaki
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000097:blood; D005091:Exons / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007536:Isomerism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009043:Motor Activity / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D007004:Hypoglycemic Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011412:Propanolamines; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D012265:Ribonucleotides; D015534:Trans-Activators; D014157:Transcription Factors; D000620:Aminoimidazole Carboxamide; C026777:ICI 118551; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide