Evidence mapPaperPMID 21921267Full record

ArticleCirculation research2011

AMP-activated protein kinase regulates E3 ligases in rodent heart.

Kedryn K Baskin, Heinrich Taegtmeyer

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

40 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.Matrix biology : journal of the International Society for Matrix Biology · 2021
    Article
  6. Proteoglycan-driven Autophagy: A Nutrient-independent Mechanism to Control Intracellular Catabolism.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020
    Review
  7. MuRF1/TRIM63, Master Regulator of Muscle Mass.International journal of molecular sciences · 2020
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Transient activation of AMPK preceding left ventricular pressure overload reduces adverse remodeling and preserves left ventricular function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  13. Article
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  15. Review
  16. Article
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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

2 authors at 1 institution in 1 country.

Kedryn K BaskinDepartment of Internal Medicine, Division of Cardiology, University of Texas Health Science Center, Houston, TX 77030, USA.
Heinrich Taegtmeyer
The University of Texas Health Science Center at Houston · US

Funding

SWITCHING OF METABOLIC GENES IN UNLOADED HEARTR01HL061483 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI TAEGTMEYER, HEINRICH · 1999 to 2021
$6.2M
NHLBI NIH HHS 5R01HL061483-9NHLBI NIH HHS R01 HL061483
6 · The paper itself

Abstract

rationaleThe degradation of proteins by the ubiquitin proteasome system (UPS) is required for the maintenance of cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). AMPK activation inhibits protein synthesis and activates autophagy, but whether AMPK plays a role in regulating protein breakdown through the UPS in the heart is not known.

objectiveTo determine whether AMPK enhances UPS-mediated protein degradation by directly regulating the ubiquitin ligases Atrogin-1 and muscle RING finger protein 1 (MuRF1) in the heart. METHODS AND

resultsNutrient deprivation and pharmacological or genetic activation of AMPK increased mRNA expression and protein levels of Atrogin-1 and MuRF1 and consequently enhanced protein degradation in neonatal cardiomyocytes. Inhibition of AMPK abrogated these effects. Using gene reporter and chromatin immunoprecipitation assays, we found that AMPK regulates MuRF1 expression by acting through the myocyte enhancer factor 2 (MEF2). We further validated these findings in vivo using MEF2-LacZ reporter mice. Furthermore, we demonstrated in adult cardiomyocytes that MuRF1 is necessary for AMPK-mediated proteolysis through the UPS in the heart. Consequently, MuRF1 knockout mice were protected from severe cardiac dysfunction during fasting.

conclusionsAMPK regulates the transcription of Atrogin-1 and MuRF1 and enhances UPS-mediated protein degradation in heart. Specifically, AMPK regulates MuRF1 through the transcription factor MEF2. The absence of MuRF1 in the heart preserves cardiac function during fasting. The results strengthen the hypothesis that AMPK serves as a modulator of intracellular protein degradation in the heart.

Indexed as

AMP-Activated Protein KinasesAnimalsAnimals, NewbornChromatin ImmunoprecipitationEnzyme ActivationGene Expression Regulation, EnzymologicGenes, ReporterGlucoseHEK293 CellsHumansMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMuscle ProteinsAMP-Activated Protein KinasesFbxo32 protein, ratGlucoseMuscle ProteinsMyogenic Regulatory FactorsRNA, MessengerSKP Cullin F-Box Protein LigasesTrim63 protein, mouseTrim63 protein, ratTripartite Motif ProteinsUbiquitin-Protein Ligases

Identifiers

PMID21921267
PMCPMC3254015
OpenAlexW2104989221

What Socratic holds

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Registered trials

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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 Socratic graph.