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Alternative splice variant PGC-1{alpha}-b is strongly induced by exercise in human skeletal muscle.
MedLine Citation:
PMID:  21862727     Owner:  NLM     Status:  Publisher    
The present study investigated whether exercise induces the expression of PGC-1αα splice variants in human skeletal muscle and the possible influence of metabolic perturbation on this response. The subjects exercised one leg for 45 min with restricted blood flow (R-leg), followed by 45 min of exercise using the other leg at the same absolute workload but with normal blood flow (NR-leg). This ischemic model (R-leg) has been shown previously to induce a greater metabolic perturbation and enhance the expression of PGC-1αα beyond that observed in the NR-leg. Cultured human myotubes were used to test suggested exercise-induced regulatory stimuli of PGC-1α. We showed, for the first time, that transcripts from both the canonical promoter (PGC-1α-a) and the proposed upstream-located promoter (PGC-1α-b) are present in human skeletal muscle. Both transcripts were upregulated after exercise in the R-leg, but the fold change increase of PGC-1α-b was much greater than that of PGC-1α-a. No differences were observed between the two conditions regarding the marker for calcineurin activation, MCIP1, or p38 phosphorylation. AMPK phosphorylation increased to a greater extent in the R-leg and AICAR stimulation of cultured human myotubes induced the expression of PGC-1α-a and PGC-1α-b. AICAR combined with norepinephrine yielded an additive effect on the PGC-1α-b expression only. Our results indicate clearly that exercise can activate an upstream promoter in humans and support AMPK as a major regulator of transcripts from the canonical PGC-1α promoter and the involvement of β-adrenergic stimulation in combination with AMPK in the regulation of PGC-1α-b.
Jessica Maria Norrbom; Eva-Karin Sällstedt; H Fischer; Carl Johan Sundberg; Helene Rundqvist; Thomas Gustafsson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-23
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Karolinska Institutet.
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