Evidence map›Paper›PMID 40445496›Full record

ArticleNeurochemical research2025

P300-Mediated ARRB1 Lactylation Promotes Mitochondrial Dysfunction and Neuronal Apoptosis in Subarachnoid Hemorrhage Via Upregulating S100A9.

Kewei Mi, Zigui Chen, Jun He, Chonghua Jiang, Ying Xia, Jun Peng

Abstract read
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Article in Neurochemical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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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

6 citing papers in PubMed.

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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

6 authors.

Kewei Mi *Department of neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, No.43, Renmin Road, Meilan District, Haikou, 570208, Hainan Province, P.R. China.
Zigui Chen *Department of neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, No.43, Renmin Road, Meilan District, Haikou, 570208, Hainan Province, P.R. China.
Jun HeDepartment of neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, No.43, Renmin Road, Meilan District, Haikou, 570208, Hainan Province, P.R. China.
Chonghua JiangDepartment of neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, No.43, Renmin Road, Meilan District, Haikou, 570208, Hainan Province, P.R. China.
Ying XiaDepartment of neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, No.43, Renmin Road, Meilan District, Haikou, 570208, Hainan Province, P.R. China.
Jun PengDepartment of neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, No.43, Renmin Road, Meilan District, Haikou, 570208, Hainan Province, P.R. China. xypengjun@126.com.

Funding

National Natural Science Foundation of China 82360249Projected by Hainan Province Cerebrovascular Disease Clinical Medical Research Center LCYX202309
6 · The paper itself

Abstract

backgroundLactylation, a novel lactate-derived posttranslational modification, has been demonstrated to be linked with brain function. The present research is intended to explore the role of β-arrestin1 (ARRB1) lactylation post-subarachnoid hemorrhage (SAH).

methodsSAH models were established in mice via intravascular puncture and in primary neurons by oxyhemoglobin (oxyHb) stimulation. Lactylome analysis identified differentially lactylated proteins. Commercial kits measured lactate, mitochondrial membrane potential, reactive oxygen species (ROS), and ATP. Mitochondrial respiration was evaluated by detecting mitochondrial oxygen consumption rate. Cell viability and apoptosis were respectively determined by CCK-8 assay and flow cytometry/TUNEL assay. Protein interactions were assessed using co-immunoprecipitation and double-label immunofluorescence.

resultsElevated lactate and ARRB1 lactylation were observed in the brain of SAH mice. In primary neurons, reducing lactate with oxamate reversed mitochondrial dysfunction and apoptosis induced by oxyHb. Overexpression of ARRB1 exacerbated oxyHb-induced neuronal injury, yet this effect was absent with the ARRB1-lysine (K) 195 arginine (R) mutant. E1A binding protein P300 (P300) promoted ARRB1 lactylation to upregulate its protein expression. P300 knockdown inhibited oxyHb-induced neuronal injury, but this inhibitory effect was counteracted by ARRB1 overexpression. In oxyHb-stimulated neurons, ARRB1 lactylation upregulated S100 calcium binding protein A9 (S100A9) protein. Additionally, ARRB1 knockdown prevented mitochondrial respiratory dysfunction in neurons induced by oxyHb, which was antagonized by recombinant S100A9. ARRB1 silencing mitigated SAH injury in mice via suppressing S100A9-mediated mitochondrial dysfunction.

conclusionP300 mediated ARRB1 lactylation, thereby increasing S100A9 to facilitate mitochondrial dysfunction and neuronal apoptosis in SAH. This study may provide prospective targets for improving SAH.

Indexed as

Apoptosisbeta-Arrestin 1Calgranulin BE1A-Associated p300 ProteinMitochondriaNeuronsSubarachnoid HemorrhageAnimalsCells, CulturedMaleMiceMice, Inbred C57BLUp-Regulationbeta-Arrestin 1Calgranulin BE1A-Associated p300 ProteinS100A9 protein, mouseApoptosisARRB1 lactylationMitochondrial dysfunctionP300S100A9Subarachnoid hemorrhage

Identifiers

PMID40445496

What Socratic holds

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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 Socratic graph.