Evidence map›Paper›PMID 30151693›Full record

ArticleCellular and molecular life sciences : CMLS2019

GADD45α alleviates acetaminophen-induced hepatotoxicity by promoting AMPK activation.

Chunmin Li, Yanan Ming, Zhengyang Wang, Qingling Xu, Lvfeng Yao, Dongke Xu, Yingyue Tang, Xiaohong Lei, Xiaobo Li, Yimin Mao

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

Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

7 citing papers in PubMed, 18 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

10 authors at 6 institutions in 1 country.

Chunmin LiDivision of Gastroenterology and Hepatology, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Yanan MingDivision of Gastroenterology and Hepatology, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Zhengyang WangDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Qingling XuDepartment of Hepatology, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Lvfeng YaoDepartment of Hepatology, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Dongke XuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Yingyue TangDivision of Gastroenterology and Hepatology, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Xiaohong LeiDivision of Gastroenterology and Hepatology, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Xiaobo LiDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. xbli@fudan.edu.cn.
Yimin MaoDivision of Gastroenterology and Hepatology, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China. maoym11968@163.com.
Shanghai Jiao Tong University · CNFudan University · CNRenji Hospital · CNFirst Affiliated Hospital of Zhengzhou University · CNFujian Medical University · CNMengchao Hepatobiliary Hospital · CN

Funding

Major Project of National Thirteenth Five Plan 2017ZX09304016Major Project of National Twelfth Five Plan (2012ZX09303-001National Natural Science Foundation of China NSFC 31771308National Natural Science Foundation of China NSFC 81670524the Shanghai Municipal Natural Science Foundation 17ZR1401800
6 · The paper itself

Abstract

As an analgesic and antipyretic drug, acetaminophen (APAP) is commonly used and known to be safe at therapeutic doses. In many countries, the overuse of APAP provokes acute liver injury and even liver failure. APAP-induced liver injury (AILI) is the most used experimental model of drug-induced liver injury (DILI). Here, we have demonstrated elevated levels of growth arrest and DNA damage-inducible 45α (GADD45α) in the livers of patients with DILI/AILI, in APAP-injured mouse livers and in APAP-treated hepatocytes. GADD45α exhibited a protective effect against APAP-induced liver injury and alleviated the accumulation of small lipid droplets in vitro and in vivo. We found that GADD45α promoted the activation of AMP-activated protein kinase α and induced fatty acid beta-oxidation, tricarboxylic acid cycle (TCA) and glycogenolysis-related gene expression after APAP exposure. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that GADD45α increased the levels of TCA cycle metabolites. Co-immunoprecipitation analysis showed that Ppp2cb, a catalytic subunit of protein phosphatase 2A, could interact directly with GADD45α. Our results indicate that hepatocyte GADD45α might represent a therapeutic target to prevent and rescue liver injury caused by APAP.

Indexed as

AcetaminophenAMP-Activated Protein KinasesAnalgesics, Non-NarcoticAnimalsAntipyreticsCell Cycle ProteinsCells, CulturedChemical and Drug Induced Liver InjuryCitric Acid CycleEnzyme ActivationFatty AcidsGADD45 ProteinsHepatocytesHumansLiverMaleAcetaminophenAMP-Activated Protein KinasesAnalgesics, Non-NarcoticAntipyreticsCell Cycle ProteinsFatty AcidsGADD45A protein, humanGadd45a protein, mouseGADD45 ProteinsNuclear ProteinsAcetaminophen (APAP)AMPKDrug-induced liver injury (DILI)GADD45α

Identifiers

PMID30151693
PMCPMC11105285
OpenAlexW2889379149

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.