Evidence map›Paper›PMID 32770173›Full record

ArticleActa pharmacologica Sinica2021

Sirtuin 3 deficiency exacerbates diabetic cardiomyopathy via necroptosis enhancement and NLRP3 activation.

Shu Song, Yue Ding, Guo-Liang Dai, Yue Zhang, Meng-Ting Xu, Jie-Ru Shen, Ting-Ting Chen, Yun Chen, Guo-Liang Meng

Open access · bronzeAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
9.5field-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

117 citing papers in PubMed, 181 citations in OpenAlex.

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  20. HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025
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57 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

9 authors at 2 institutions in 1 country.

Shu Song *Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Yue Ding *Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Guo-Liang Dai *Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
Yue ZhangDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Meng-Ting XuDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Jie-Ru ShenDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Ting-Ting ChenDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Yun ChenDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Guo-Liang MengDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China. mengguoliang@ntu.edu.cn.
Nantong University · CNNanjing University of Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sirtuin 3 (SIRT3) is a potential therapeutic target for cardiovascular, metabolic, and other aging-related diseases. In this study, we investigated the role of SIRT3 in diabetic cardiomyopathy (DCM). Mice were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes mellitus. Our proteomics analysis revealed that SIRT3 expression in the myocardium of diabetic mice was lower than that of control mice, as subsequently confirmed by real-time PCR and Western blotting. To explore the role of SIRT3 in DCM, SIRT3-knockout mice and 129S1/SvImJ wild-type mice were injected with STZ. We found that diabetic mice with SIRT3 deficiency exhibited aggravated cardiac dysfunction, increased lactate dehydrogenase (LDH) level in the serum, decreased adenosine triphosphate (ATP) level in the myocardium, exacerbated myocardial injury, and promoted myocardial reactive oxygen species (ROS) accumulation. Neonatal rat cardiomyocytes were transfected with SIRT3 siRNA, then exposed to high glucose (HG, 25.5 mM). We found that downregulation of SIRT3 further increased LDH release, decreased ATP level, suppressed the mitochondrial membrane potential, and elevated oxidative stress in HG-treated cardiomyocytes. SIRT3 deficiency further raised expression of necroptosis-related proteins including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and cleaved caspase 3, and upregulated the expression of inflammation-related proteins including NLR family pyrin domain-containing protein 3 (NLRP3), caspase 1 p20, and interleukin-1β both in vitro and in vivo. Collectively, SIRT3 deficiency aggravated hyperglycemia-induced mitochondrial damage, increased ROS accumulation, promoted necroptosis, possibly activated the NLRP3 inflammasome, and ultimately exacerbated DCM in the mice. These results suggest that SIRT3 can be a molecular intervention target for the prevention and treatment of DCM.

Indexed as

AnimalsDiabetes Mellitus, ExperimentalDiabetic CardiomyopathiesInflammasomesMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumMyocytes, CardiacNecroptosisNLR Family, Pyrin Domain-Containing 3 ProteinOxidative StressRatsRats, Sprague-DawleySirtuin 3InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseSirt3 protein, mouseSirtuin 3Streptozocindiabetic cardiomyopathymitochondrianecroptosisNLRP3RIPK3ROSSirtuin 3

Identifiers

PMID32770173
PMCPMC8027053
OpenAlexW3048252338

What OpenQuestion holds

Textmetadata
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.