Evidence map›Paper›PMID 25475100›Full record

ArticleJournal of cellular physiology2015

HDAC4 degradation mediates HDAC inhibition-induced protective effects against hypoxia/reoxygenation injury.

Jianfeng Du, Ling Zhang, Shougang Zhuang, Gang Jian Qin, Ting Cun Zhao

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 22% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. The ChickenGenes · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Critical Functions of Histone Deacetylases (HDACs) in Modulating Inflammation Associated with Cardiovascular Diseases.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022
    Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. SUMOylation as a Therapeutic Target for Myocardial Infarction.Frontiers in cardiovascular medicine · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review
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

5 authors at 3 institutions in 1 country.

Jianfeng DuDepartment of Surgery, Boston University Medical School, Boston University, Roger Williams Medical Center, Providence, Rhode Island.
Ling Zhang
Shougang Zhuang
Gang Jian Qin
Ting Cun Zhao
Boston University · USBrown University · USNorthwestern University · US

Funding

Histone Deacetylase Inhibition: A Novel Approach to CardioprotectionR01HL089405 · NHLBI · ROGER WILLIAMS MEDICAL CENTER · PI ZHAO, TING C · 2009 to 2020
$3.4M
p38 acetylation: Novel signaling mechanisms and myocardial protectionR01HL115265 · NHLBI · ROGER WILLIAMS MEDICAL CENTER · PI ZHAO, TING C · 2013 to 2016
$1.6M
NHLBI NIH HHS R01 HL089405NHLBI NIH HHS R01 HL115265
6 · The paper itself

Abstract

Histone deacetylases (HDACs) play a crucial role in the regulation of gene expression through remodeling of chromatin structures. However, the molecular mechanisms involved in this event remain unknown. In this study, we sought to examine whether HDAC inhibition-mediated protective effects involved HDAC4 sumoylation, degradation, and the proteasome pathway. Isolated neonatal mouse ventricular myocytes (NMVM) and H9c2 cardiomyoblasts were subjected to 48 h of hypoxia (H) (1% O2 ) and 2 h of reoxygenation (R). Treatment of cardiomyocytes with trichostatin A (TSA) attenuated H/R-elicited injury, as indicated by a reduction of lactate dehydrogenase (LDH) leakage, an increase in cell viability, and decrease in apoptotic positive cardiomyocytes. MG132, a potent proteasome pathway inhibitor, abrogated TSA-induced protective effects, which was associated with the accumulation of ubiquitinated HDAC4. NMVM transduced with adenoviral HDAC4 led to an exaggeration of H/R-induced injury. TSA treatment resulted in a decrease in HDAC4 in cardiomyocytes infected with adenoviral HDAC4, and HDAC4-induced injury was attenuated by TSA. HDAC inhibition resulted in a significant reduction in reactive oxygen species (ROS) in cardiomyoblasts exposed to H/R, which was attenuated by blockade of the proteasome pathway. Cardiomyoblasts carrying wild type and sumoylation mutation (K559R) were established to examine effects of HDAC4 sumoylation and ubiquitination on H/R injury. Disruption of HDAC4 sumoylation brought about HDAC4 accumulation and impairment of HDAC4 ubiquitination in association with enhanced susceptibility of cardiomyoblasts to H/R. Taken together, these results demonstrated that HDAC inhibition stimulates proteasome dependent degradation of HDAC4, which is associated with HDAC4 sumoylation to induce these protective effects.

Indexed as

AnimalsAnimals, NewbornHistone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsHypoxiaMiceMyocardial InfarctionMyocardial Reperfusion InjuryMyocytes, CardiacProteolysisReactive Oxygen SpeciesHdac5 protein, mouseHistone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsReactive Oxygen Speciestrichostatin A

Identifiers

PMID25475100
PMCPMC4373665
OpenAlexW2103092453

What OpenQuestion holds

Textmetadata
LicenceTDM
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.