Evidence map›Paper›PMID 21871561›Full record

ArticleFree radical biology & medicine2011

AMP-dependent kinase and autophagic flux are involved in aldehyde dehydrogenase-2-induced protection against cardiac toxicity of ethanol.

Wei Ge, Rui Guo, Jun Ren

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

Article in Free radical biology & medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.6field-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

28 citing papers in PubMed, 77 citations in OpenAlex.

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  9. Experimental and therapeutic medicine · 2020
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  10. Article
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  12. Cardiac Toxicity From Ethanol Exposure in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2019
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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

3 authors at 2 institutions in 2 countries.

Wei GeDepartment of Geriatrics, Fourth Military Medical University, Xi'an, Shaan-xi 710032, China.
Rui Guo
Jun Ren
University of Wyoming · USAir Force Medical University · CN

Funding

Role of Acetaldehyde in Alcoholic CardiomyopathyR01AA013412 · NIAAA · UNIVERSITY OF WYOMING · PI REN, JUN · 2004 to 2008
$1.0M
NIAAA NIH HHS 1R01 AA013412NIAAA NIH HHS R01 AA013412
6 · The paper itself

Abstract

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) alleviates ethanol toxicity although the precise mechanism is unclear. This study was designed to evaluate the effect of ALDH2 on ethanol-induced myocardial damage with a focus on autophagy. Wild-type FVB and transgenic mice overexpressing ALDH2 were challenged with ethanol (3g/kg/day, ip) for 3days and cardiac mechanical function was assessed using the echocardiographic and IonOptix systems. Western blot analysis was used to evaluate essential autophagy markers, Akt and AMPK, and the downstream signal mTOR. Ethanol challenge altered cardiac geometry and function as evidenced by enlarged ventricular end systolic and diastolic diameters, decreased cell shortening and intracellular Ca(2+) rise, prolonged relengthening and intracellular Ca(2+) decay, as well as reduced SERCA Ca(2+) uptake, which effects were mitigated by ALDH2. Ethanol challenge facilitated myocardial autophagy as evidenced by enhanced expression of Beclin, ATG7, and LC3B II, as well as mTOR dephosphorylation, which was alleviated by ALDH2. Ethanol challenge-induced cardiac defect and apoptosis were reversed by the ALDH2 agonist Alda-1, the autophagy inhibitor 3-MA, and the AMPK inhibitor compound C, whereas the autophagy inducer rapamycin and the AMPK activator AICAR mimicked or exacerbated ethanol-induced cell injury. Ethanol promoted or suppressed phosphorylation of AMPK and Akt, respectively, in FVB but not ALDH2 murine hearts. Moreover, AICAR nullified Alda-1-induced protection against ethanol-triggered autophagic and functional changes. Ethanol increased GFP-LC3 puncta in H9c2 cells, the effect of which was ablated by Alda-1 and 3-MA. Lysosomal inhibition using bafilomycin A1, E64D, and pepstatin A obliterated Alda-1- but not ethanol-induced responses in GFP-LC3 puncta. Our results suggest that ALDH2 protects against ethanol toxicity through altered Akt and AMPK signaling and regulation of autophagic flux.

Indexed as

Aldehyde DehydrogenaseAldehyde Dehydrogenase, MitochondrialAnimalsAutophagyBenzamidesBenzodioxolesCell LineEchocardiographyEthanolMaleMiceMice, Inbred StrainsMice, TransgenicMyocardiumMyocytes, CardiacPhosphotransferases (Phosphate Group Acceptor)Aldehyde DehydrogenaseAldehyde Dehydrogenase, MitochondrialALDH2 protein, mouseAMP-dependent kinase (ATP-forming)BenzamidesBenzodioxolesEthanolN-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamidePhosphotransferases (Phosphate Group Acceptor)

Identifiers

PMID21871561
PMCPMC3188331
OpenAlexW2072307557

What OpenQuestion holds

Textmetadata
LicenceTDM
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.