Evidence map›Paper›PMID 18974883›Full record

ArticlePloS one2008

AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells.

Isabella Irrcher, Vladimir Ljubicic, Angie F Kirwan, David A Hood

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 2 pooled it
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 209 citations in OpenAlex.

  1. Pooled it
  2. A systematic review of p53 regulation of oxidative stress in skeletal muscle.Redox report : communications in free radical research · 2018
    Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Mitochondrial Biogenesis in Skeletal Muscle.Advances in experimental medicine and biology · 2025
    Review
  15. Article
  16. Review
  17. Review
  18. The Molecular Mechanism ofPlants (Basel, Switzerland) · 2023
    Article
  19. Review
  20. Article

47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Isabella IrrcherDepartment of Biology, York University, Toronto, Ontario, Canada.
Vladimir Ljubicic
Angie F Kirwan
David A Hood
York University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mechanisms by which PGC-1alpha gene expression is controlled in skeletal muscle remains largely undefined. Thus, we sought to investigate the transcriptional regulation of PGC-1alpha using AICAR, an activator of AMPK, that is known to increase PGC-1alpha expression. A 2.2 kb fragment of the human PGC-1alpha promoter was cloned and sequence analysis revealed that this TATA-less sequence houses putative consensus sites including a GC-box, a CRE, several IRSs, a SRE, binding sites for GATA, MEF2, p 53, NF-kappaB, and EBox binding proteins. AMPK activation for 24 hours increased PGC-1alpha promoter activity with concomitant increases in mRNA expression. The effect of AICAR on transcriptional activation was mediated by an overlapping GATA/EBox binding site at -495 within the PGC-1alpha promoter based on gel shift analyses that revealed increases in GATA/EBox DNA binding. Mutation of the EBox within the GATA/EBox binding site in the promoter reduced basal promoter activity and completely abolished the AICAR effect. Supershift analyses identified USF-1 as a DNA binding transcription factor potentially involved in regulating PGC-1alpha promoter activity, which was confirmed in vivo by ChIP. Overexpression of either GATA-4 or USF-1 alone increased the p851 PGC-1alpha promoter activity by 1.7- and 2.0-fold respectively, while co-expression of GATA-4 and USF-1 led to an additive increase in PGC-1alpha promoter activity. The USF-1-mediated increase in PGC-1alpha promoter activation led to similar increases at the mRNA level. Our data identify a novel AMPK-mediated regulatory pathway that regulates PGC-1alpha gene expression. This could represent a potential therapeutic target to control PGC-1alpha expression in skeletal muscle.

Indexed as

Promoter Regions, GeneticTranscriptional ActivationAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsBase SequenceBinding SitesCells, CulturedDNA-Binding ProteinsE-Box ElementsEnzyme InhibitorsGATA4 Transcription FactorHeat-Shock ProteinsHumansMiceMolecular Sequence DataAICA ribonucleotideAminoimidazole CarboxamideAMP-Activated Protein KinasesDNA-Binding ProteinsEnzyme InhibitorsGATA4 Transcription FactorHeat-Shock ProteinsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, humanRibonucleotidesTranscription FactorsUpstream Stimulatory FactorsUSF1 protein, human

Identifiers

PMID18974883
PMCPMC2570798
OpenAlexW2137737168

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.