Evidence map›Paper›PMID 38365969›Full record

ArticleCell death and differentiation2024

Set7/9 aggravates ischemic brain injury via enhancing glutamine metabolism in a blocking Sirt5 manner.

Jinghuan Wang, Subei Tan, Yuyu Zhang, Jie Xu, Yuhui Li, Qianwen Cheng, Chen Ding, Xinhua Liu, Jun Chang

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

Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
4.8field-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

10 citing papers in PubMed, 14 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Jinghuan Wang *Shanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Subei Tan *Shanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Yuyu ZhangShanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Jie XuShanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Yuhui LiShanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Qianwen ChengShanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Chen DingState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, 201203, China. chend@fudan.edu.cn.
Xinhua LiuShanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China. liuxinhua@fudan.edu.cn.ORCID 0000-0002-9972-8215
Jun ChangShanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China. jchang@fudan.edu.cn.
Fudan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The aberrant expression of methyltransferase Set7/9 plays a role in various diseases. However, the contribution of Set7/9 in ischemic stroke remains unclear. Here, we show ischemic injury results in a rapid elevation of Set7/9, which is accompanied by the downregulation of Sirt5, a deacetylase reported to protect against injury. Proteomic analysis identifies the decrease of chromobox homolog 1 (Cbx1) in knockdown Set7/9 neurons. Mechanistically, Set7/9 promotes the binding of Cbx1 to H3K9me2/3 and forms a transcription repressor complex at the Sirt5 promoter, ultimately repressing Sirt5 transcription. Thus, the deacetylation of Sirt5 substrate, glutaminase, which catalyzes the hydrolysis of glutamine to glutamate and ammonia, is decreased, promoting glutaminase expression and triggering excitotoxicity. Blocking Set7/9 eliminates H3K9me2/3 from the Sirt5 promoter and normalizes Sirt5 expression and Set7/9 knockout efficiently ameliorates brain ischemic injury by reducing the accumulation of ammonia and glutamate in a Sirt5-dependent manner. Collectively, the Set7/9-Sirt5 axis may be a promising epigenetic therapeutic target.

Indexed as

Brain IschemiaGlutamineHistone-Lysine N-MethyltransferaseSirtuinsAnimalsHumansMaleMiceMice, Inbred C57BLMice, KnockoutNeuronsPromoter Regions, GeneticGlutamineHistone-Lysine N-MethyltransferaseSetd7 protein, mouseSIRT5 protein, mouseSirtuins

Identifiers

PMID38365969
PMCPMC11043079
OpenAlexW4391881792

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.