Evidence map›Paper›PMID 24959866›Full record

ArticlePloS one2014

Autophagic-lysosomal inhibition compromises ubiquitin-proteasome system performance in a p62 dependent manner in cardiomyocytes.

Zongwen Tian, Changhua Wang, Chengjun Hu, Yihao Tian, Jinbao Liu, Xuejun Wang

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
4.5field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Article
  4. Article
  5. Article
  6. Review
  7. Protein homeostasis in the aged and diseased heart.The journal of cardiovascular aging · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Autophagy modulation: a potential therapeutic approach in cardiac hypertrophy.American journal of physiology. Heart and circulatory physiology · 2017
    Review
  17. Article
  18. Review
  19. Article
  20. Contribution of p62 to Phenotype Transition of Coronary Arterial Myocytes with Defective Autophagy.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2017
    Article
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

6 authors at 2 institutions in 2 countries.

Zongwen TianDivision of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota, United States of America.
Changhua WangDivision of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota, United States of America.
Chengjun HuDivision of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota, United States of America.
Yihao TianDivision of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota, United States of America.
Jinbao LiuProtein Modification and Degradation Laboratory, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangzhou, Guangdong, China.
Xuejun WangDivision of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota, United States of America.
University of South Dakota · USGuangzhou Medical University · CN

Funding

Ubiquitin receptors and cardiac proteotoxicityR01HL072166 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI WANG, XUEJUN · 2003 to 2023
$6.9M
The COP9 SIgnalosome in the HeartR01HL085629 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI WANG, XUEJUN · 2006 to 2019
$4.7M
NHLBI NIH HHS R01 HL072166NHLBI NIH HHS R01HL072166NHLBI NIH HHS R01 HL085629NHLBI NIH HHS R01HL085629
6 · The paper itself

Abstract

Intracellular protein degradation is primarily performed by the ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP). The interplay between these two pathways has been rarely examined in intact animals and the mechanism underlying the interplay remains unclear. Hence, we sought to test in vivo and in vitro the impact of inhibition of the ALP on UPS proteolytic performance in cardiomyocytes and to explore the underlying mechanism. Transgenic mice ubiquitously expressing a surrogate UPS substrate (GFPdgn) were treated with bafilomycin-A1 (BFA) to inhibit the ALP. Myocardial and renal GFPdgn protein levels but not mRNA levels were increased at 24 hours but not 3 hours after the first injection of BFA. Myocardial protein abundance of key proteasome subunits and the activities of proteasomal peptidases were not discernibly altered by the treatment. In cultured neonatal rat ventricular myocytes (NRVMs), the surrogate UPS substrate GFPu and a control red fluorescence protein (RFP) were co-expressed to probe UPS performance. At 12 hours or 24 hours after ALP inhibition by 3-methyladenine (3-MA) or BFA, GFPu/RFP protein ratios and the protein half-life of GFPu were significantly increased, which is accompanied by increases in p62 proteins. Similar findings were obtained when ALP was inhibited genetically via silencing Atg7 or Rab7. ALP inhibition-induced increases in GFPu and p62 are co-localized in NRVMs. siRNA-mediated p62 knockdown prevented ALP inhibition from inducing GFPu accumulation in NRVMs. We conclude that in a p62-dependent fashion, ALP inhibition impairs cardiac UPS proteolytic performance in cardiomyocytes in vitro and in vivo.

Indexed as

AutophagyAdenineAnimalsAntineoplastic AgentsBoronic AcidsBortezomibHeat-Shock ProteinsLysosomesMiceMice, TransgenicMyocytes, CardiacProteasome Endopeptidase ComplexProteasome InhibitorsProteolysisPyrazinesRats3-methyladenineAdenineAntineoplastic AgentsBoronic AcidsBortezomibHeat-Shock ProteinsProteasome Endopeptidase ComplexProteasome InhibitorsPyrazinesSequestosome-1 ProteinSqstm1 protein, ratUbiquitin

Identifiers

PMID24959866
PMCPMC4069113
OpenAlexW2047703551

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.