Evidence map›Paper›PMID 24483773›Full record

ArticleAlcoholism, clinical and experimental research2014

PKCε contributes to chronic ethanol-induced steatosis in mice but not inflammation and necrosis.

J Phillip Kaiser, Luping Guo, Juliane I Beier, Jun Zhang, Aruni Bhatnagar, Gavin E Arteel

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

Article in Alcoholism, clinical and experimental research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 85% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
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 at 2 institutions in 1 country.

J Phillip KaiserDepartment of Pharmacology and Toxicology , University of Louisville Health Sciences Center, Louisville, Kentucky; University of Louisville Alcohol Research Center , Louisville, Kentucky.
Luping Guo
Juliane I Beier
Jun Zhang
Aruni Bhatnagar
Gavin E Arteel
University of Louisville · USUniversity of California, Los Angeles · US

Funding

UOFL ENVIRONMENTAL HEALTH SCIENCES TRAINING PROGRAMT32ES011564 · NIEHS · UNIVERSITY OF LOUISVILLE · PI David W Hein, John Pierce Wise · 2004 to 2026
$7.1M
Role of Platelet Activation and Vascular Pathology in Aldehyde ToxicityP01ES011860 · NIEHS · UNIVERSITY OF LOUISVILLE · PI BHATNAGAR, ARUNI BHATNAGAR · 2003 to 2007
$7.0M
CONTROL OF DRUG AND ETHANOL METABOLISMR01AA003624 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI ARTEEL, GAVIN E · 1985 to 2010
$2.3M
Priming of liver disease by arsenic exposureR21ES016367 · NIEHS · UNIVERSITY OF LOUISVILLE · PI ARTEEL, GAVIN E · 2009 to 2010
$406k
CONTROL OF DRUG AND ETHANOL METABOLISMR37AA003624 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI THURMAN, RONALD G · 1999 to 2000
$280k
The role of PKC epsilon in alcoholic liver diseaseF31AA017346 · NIAAA · UNIVERSITY OF LOUISVILLE · PI KAISER, JONATHAN PHILLIP · 2007 to 2010
$71k
NIAAA NIH HHS AA003624NIAAA NIH HHS F31 AA017346NIAAA NIH HHS R01 AA003624NIAAA NIH HHS R37 AA003624NIEHS NIH HHS ES11860NIEHS NIH HHS P01 ES011860NIEHS NIH HHS R21 ES016367NIEHS NIH HHS T32 ES011564
6 · The paper itself

Abstract

backgroundProtein kinase C epsilon (PKCε) has been shown to play a role in experimental steatosis by acute alcohol. The "two-hit" hypothesis implies that preventing steatosis should blunt more advanced liver damage (e.g., inflammation and necrosis). However, the role of PKCε in these pathologies is not yet known. The goal of this current work was to address this question in a model of chronic alcohol exposure using antisense oligonucleotides (ASO) against PKCε.

methodsAccordingly, PKCε ASO- and saline-treated mice were fed high-fat control or ethanol (EtOH)-containing enteral diets for 4 weeks.

resultsChronic EtOH exposure significantly elevated hepatic lipid pools as well as activated PKCε. The PKCε ASO partially blunted the increases in hepatic lipids caused by EtOH. Administration of PKCε ASO also completely prevented the increase in the expression of fatty acid synthase, and tumor necrosis factor α caused by EtOH. Despite these protective effects, the PKCε ASO was unable to prevent the increases in inflammation and necrosis caused by chronic EtOH. These latter results correlated with an inability of the PKCε ASO to blunt the up-regulation of plasminogen activator inhibitor-1 (PAI-1) and the accumulation of fibrin. Importantly, PAI-1 has been previously shown to more robustly mediate inflammation and necrosis (vs. steatosis) after chronic EtOH exposure.

conclusionsThis study identifies a novel potential mechanism where EtOH, independent of steatosis, can contribute to liver damage. These results also suggest that PAI-1 and fibrin accumulation may be at the center of this PKCε-independent pathway.

Indexed as

AnimalsBiomarkersBody WeightCentral Nervous System DepressantsDiglyceridesEnzyme ActivationEthanolFatty Liver, AlcoholicFibrinGene ExpressionHepatitis, AlcoholicLipid MetabolismLiverMaleMiceMice, Inbred C57BLBiomarkersCentral Nervous System DepressantsDiglyceridesEthanolFibrinPrkce protein, mouseProtein Kinase C-epsilonAlcoholAlcoholic Liver DiseaseInflammationProtein Kinase CSteatosis

Identifiers

PMID24483773
PMCPMC4157371
OpenAlexW2130668011

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.