Evidence map›Paper›PMID 18250163›Full record

ArticleThe Journal of biological chemistry2008

HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity.

Mahesh P Gupta, Sadhana A Samant, Stephen H Smith, Sanjeev G Shroff

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06660784 (Mechanism of Nitric Oxide on Ventilator-induced Diaphragm Dysfunction with Extracorporeal Membrane Lung Assistance), which is not on this map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% 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.

NCT06660784 active not recruitingnot on this mapstarted 2024, after this paper: background citation

Mechanism of Nitric Oxide on Ventilator-induced Diaphragm Dysfunction with Extracorporeal Membrane Lung Assistance

TypeobservationalSponsorZhongnan HospitalRan2024 to 2025Enrolled80ConditionsTracheal Intubation, Extracorporeal Membrane Oxygenation, Nitric Oxide, Ventilator-induced Diaphragmatic DysfunctionArmsNitric Oxide
3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Glycation in the cardiomyocyte.Vitamins and hormones · 2024
    Review
  6. Cytoskeletal association of ATP citrate lyase controls the mechanodynamics of macropinocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Role of Muscle LIM Protein in Mechanotransduction Process.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Nitric oxide and skeletal muscle contractile function.Nitric oxide : biology and chemistry · 2022
    Review
  10. Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022
    Review
  11. Review
  12. Article
  13. Article
  14. Protein acetylation in cardiac aging.Journal of molecular and cellular cardiology · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. Epigenetics and Heart Failure.International journal of molecular sciences · 2020
    Review
  19. Article
  20. Article

29 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 2 institutions in 1 country.

Mahesh P GuptaDepartment of Surgery, Committee on Molecular Medicine, Biological Science Division, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. mgupta@surgery.bsd.uchicago.edu
Sadhana A Samant
Stephen H Smith
Sanjeev G Shroff
University of Chicago · USUniversity of Pittsburgh · US

Funding

The Role of PARP-SIR2 Signaling in Heart FailureR01HL083423 · NHLBI · UNIVERSITY OF CHICAGO · PI GUPTA, MAHESH P · 2007 to 2011
$2.4M
Histone deacetylases in pathogenesis of heart failureR01HL077788 · NHLBI · UNIVERSITY OF CHICAGO · PI GUPTA, MAHESH P · 2004 to 2007
$2.0M
Alpha-Myosin Heavy Chain Gene Repression &Heart FailureR01HL068083 · NHLBI · UNIVERSITY OF CHICAGO · PI GUPTA, MAHESH P · 2001 to 2004
$1.2M
NHLBI NIH HHS HL 77788NHLBI NIH HHS HL 83423NHLBI NIH HHS R01 HL068083NHLBI NIH HHS R01 HL077788NHLBI NIH HHS R01 HL083423NHLBI NIH HHS R01 HL 68083
6 · The paper itself

Abstract

Reversible acetylation of lysine residues within a protein is considered a biologically relevant modification that rivals phosphorylation ( Kouzarides, T. (2000) EMBO J. 19, 1176-1179 ). The enzymes responsible for such protein modification are called histone acetyltransferases (HATs) and deacetylases (HDACs). A role of protein phosphorylation in regulating muscle contraction is well established ( Solaro, R. J., Moir, A. J., and Perry, S. V. (1976) Nature 262, 615-617 ). Here we show that reversible protein acetylation carried out by HATs and HDACs also plays a role in regulating the myofilament contractile activity. We found that a Class II HDAC, HDAC4, and an HAT, PCAF, associate with cardiac myofilaments. Primary cultures of cardiomyocytes as well as mouse heart sections examined by immunohistochemical and electron microscopic analyses revealed that both HDAC4 and PCAF associate with the Z-disc and I- and A-bands of cardiac sarcomeres. Increased acetylation of sarcomeric proteins by HDAC inhibition (using class I and II HDAC inhibitors or anti-HDAC4 antibody) enhanced the myofilament calcium sensitivity. We identified the Z-disc-associated protein, MLP, a sensor of cardiac mechanical stretch, as an acetylated target of PCAF and HDAC4. We also show that trichostatin-A, a class I and II HDAC inhibitor, increases myofilament calcium sensitivity of wild-type, but not of MLP knock-out mice, thus demonstrating a role of MLP in acetylation-dependent increased contractile activity of myofilaments. These studies provide the first evidence that HATs and HDACs play a role in regulation of muscle contraction.

Indexed as

Actin CytoskeletonAnimalsCalciumEnzyme InhibitorsHistone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsLIM Domain ProteinsMiceMice, KnockoutMuscle ProteinsMyocardial ContractionMyocardiumMyocytes, Cardiacp300-CBP-Associated Factorp300-CBP Transcription FactorsCalciumcysteine and glycine-rich protein 3Enzyme InhibitorsHdac5 protein, mouseHistone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsLIM Domain ProteinsMarcksl1 protein, ratMuscle Proteinsp300-CBP-Associated Factorp300-CBP Transcription Factorstrichostatin AVesicular Transport Proteins

Identifiers

PMID18250163
PMCPMC2442284
OpenAlexW2019483572

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.