Evidence map›Paper›PMID 35452917›Full record

ArticleRedox biology2022

Cardiac SIRT1 ameliorates doxorubicin-induced cardiotoxicity by targeting sestrin 2.

Jie Wang A, Yufeng Tang, Jingjing Zhang, Jie Wang B, Mengjie Xiao, Guangping Lu, Jiahao Li, Qingbo Liu, Yuanfang Guo, Junlian Gu

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
13.7field-weighted citation impact, top 1% 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

58 citing papers in PubMed, 93 citations in OpenAlex.

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  8. FOXO1-NMNAT3 axis dysregulation promotes doxorubicin cardiotoxicity: NADRedox report : communications in free radical research · 2025
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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

10 authors at 3 institutions in 1 country.

Jie Wang ASchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Yufeng TangDepartment of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, 250014, China.
Jingjing ZhangDepartment of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, 110016, China; Department of Cardiology, The People's Hospital of Liaoning Province, Shenyang, Liaoning, 110016, China.
Jie Wang BSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Mengjie XiaoSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Guangping LuSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Jiahao LiSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Qingbo LiuSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Yuanfang GuoSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Junlian GuSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address: junlian_gu@sdu.edu.cn.
Shandong University · CNLiaoning Provincial People's Hospital · CNShandong First Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although it is known that the expression and activity of sirtuin 1 (SIRT1) significantly decrease in doxorubicin (DOX)-induced cardiomyopathy, the role of interaction between SIRT1 and sestrin 2 (SESN2) is largely unknown. In this study, we investigated whether SESN2 could be a crucial target of SIRT1 and the effect of their regulatory interaction and mechanism on DOX-induced cardiac injury. Here, using DOX-treated cardiomyocytes and cardiac-specific Sirt1 knockout mice models, we found SIRT1 deficiency aggravated DOX-induced cardiac structural abnormalities and dysfunction, whereas the activation of SIRT1 by resveratrol (RES) treatment or SIRT1 overexpression possessed cardiac protective effects. Further studies indicated that SIRT1 exerted these beneficial effects by markedly attenuating DOX-induced oxidative damage and apoptosis in a SESN2-dependent manner. Knockdown of Sesn2 impaired RES/SIRT1-mediated protective effects, while upregulation of SESN2 efficiently rescued DOX-induced oxidative damage and apoptosis. Most importantly, SIRT1 activation could reduce DOX-induced SESN2 ubiquitination possibly through reducing the interaction of SESN2 with mouse double minute 2 (MDM2). The recovery of SESN2 stability in DOX-impaired primary cardiomyocytes by SIRT1 was confirmed by Mdm2-siRNA transfection. Taken together, our findings indicate that disrupting the interaction between SESN2 and MDM2 by SIRT1 to reduce the ubiquitination of SESN2 is a novel regulatory mechanism for protecting hearts from DOX-induced cardiotoxicity and suggest that the activation of SIRT1-SESN2 axis has potential as a therapeutic approach to prevent DOX-induced cardiotoxicity.

Indexed as

CardiomyopathiesCardiotoxicityAnimalsApoptosisDoxorubicinMiceMyocytes, CardiacOxidative StressSestrinsSirtuin 1DoxorubicinSestrinsSirt1 protein, mouseSirtuin 1ApoptosisCardiotoxicityDoxorubicinOxidative stressSESN2SIRT1

Identifiers

PMID35452917
PMCPMC9043985
OpenAlexW4224308286

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.