Evidence map›Paper›PMID 39719406›Full record

ArticleJournal of the American Heart Association2025

Diacylglycerol Kinase ζ Attenuates Doxorubicin-Induced Cardiotoxicity Through p53 Degradation.

Shingo Tachibana, Yoichiro Otaki, Tetsu Watanabe, Jun Goto, Haruki Ochi, Toshiaki Tanaka, Hiroe Ono, Ryuhei Yamaguchi, Junya Sato, Hiroki Takahashi and 3 more

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. A novel mouse model of adenine-supplemented high-fat diet induced cardiovascular-kidney-metabolic syndrome.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Ubiquitin E3 Ligases and p53 in Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2025
    Review
  7. Article
  8. 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

13 authors.

Shingo TachibanaDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.ORCID 0009-0004-6368-6510
Yoichiro OtakiDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.ORCID 0000-0001-7859-1427
Tetsu WatanabeDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.ORCID 0000-0002-4565-3799
Jun GotoDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.ORCID 0009-0008-9113-5969
Haruki OchiInstitute for Promotion of Medical Science Research, Faculty of Medicine Yamagata University Yamagata Japan.ORCID 0000-0002-0088-581X
Toshiaki TanakaDepartment of Anatomy and Cell Biology, School of Medicine Yamagata University Yamagata Japan.ORCID 0000-0003-1329-838X
Hiroe OnoDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.
Ryuhei YamaguchiDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.ORCID 0009-0002-1958-239X
Junya SatoDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.ORCID 0009-0006-0454-3880
Hiroki TakahashiDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.
Takanori ArimotoDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.ORCID 0000-0003-2802-0794
Kaoru GotoDepartment of Anatomy and Cell Biology, School of Medicine Yamagata University Yamagata Japan.
Masafumi WatanabeDepartment of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDoxorubicin-induced cardiotoxicity is still an important medical problem associated with a high mortality rate in cancer survivors. p53 plays a key role in doxorubicin-induced cardiotoxicity. Diacylglycerol kinase ζ (Dgkζ), a 130-kDa enzyme abundant in cardiomyocytes, regulates the p53 protein expression level in neurons. To elucidate the mechanism of doxorubicin-induced cardiotoxicity, we focused on the functional role of Dgkζ and its interaction with heat shock protein 70 (Hsp70)-related ubiquitin E3 ligases such as E6-associated protein (E6ap) and C-terminus of Hsp70-interacting protein. METHODS AND

resultsProtein interactions of Dgkζ with Hsp70 and E6ap were confirmed by immunoprecipitation, but not C-terminus of Hsp70-interacting protein. We administered doxorubicin in cardiac-specific overexpression of Dgkζ transgenic (Dgkζ-Tg) mice and wild-type littermates. Dgkζ-Tg mice showed lower p53 protein expression levels, preserved cardiac function, and improved survival rates compared with wild-type littermates after doxorubicin administration. RNA sequence analysis of myocardial tissues from Dgkζ-Tg after doxorubicin stimulation identified

conclusionsWe demonstrated for the first time that Dgkζ augments p53 ubiquitin-proteasome degradation and ameliorates doxorubicin-induced cardiotoxicity by interacting with Hsp70 and E3 ligases such as E6ap and C-terminus of Hsp70-interacting protein.

Indexed as

Antibiotics, AntineoplasticApoptosisCardiotoxicityDiacylglycerol KinaseDoxorubicinHSP70 Heat-Shock ProteinsMice, TransgenicMyocytes, CardiacTumor Suppressor Protein p53AnimalsCells, CulturedDisease Models, AnimalHeart DiseasesMaleMiceMice, Inbred C57BLAntibiotics, AntineoplasticDiacylglycerol Kinasediacylglycerol kinase zeta, mouseDoxorubicinHSP70 Heat-Shock ProteinsProteasome Endopeptidase ComplexTrp53 protein, mouseTumor Suppressor Protein p53chipDgkζdoxorubicin cardiotoxicityE6apHsp70p53ubiquitin‐proteasome system

Identifiers

PMID39719406
PMCPMC12054516

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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 OpenQuestion graph.