Evidence map›Paper›PMID 23519123›Full record

ArticleCell death & disease2013

Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc/jnk/sp1 pathway.

M Jin, A Ande, A Kumar, S Kumar

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

93 citing papers in PubMed, 172 citations in OpenAlex.

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33 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

M JinDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
A Ande
A Kumar
S Kumar
University of Missouri–Kansas City · US

Funding

Alcohol Abuse and HIV-mediated NeurotoxicityR01AA020806 · NIAAA · UNIVERSITY OF MISSOURI KANSAS CITY · PI WANG, JIANPING · 2012 to 2016
$1.7M
Tobacco/nicotine, cytochrome P450, and HIV-1R21DA031616 · NIDA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KUMAR, SANTOSH · 2011 to 2012
$413k
NIAAA NIH HHS AA020806NIAAA NIH HHS R01 AA020806NIDA NIH HHS DA031616NIDA NIH HHS R21 DA031616
6 · The paper itself

Abstract

CYP2E1 metabolizes ethanol leading to production of reactive oxygen species (ROS) and acetaldehyde, which are known to cause not only liver damage but also toxicity to other organs. However, the signaling pathways involved in CYP2E1 regulation by ethanol are not clear, especially in extra-hepatic cells. This study was designed to examine the role of CYP2E1 in ethanol-mediated oxidative stress and cytotoxicity, as well as signaling pathways by which ethanol regulates CYP2E1 in extra-hepatic cells. In this study, we used astrocytic and monocytic cell lines, because they are important cells in central nervous system . Our results showed that 100 mM ethanol significantly induced oxidative stress, apoptosis, and cell death at 24 h in the SVGA astrocytic cell line, which was rescued by a CYP2E1 selective inhibitor, diallyl sulfide (DAS), CYP2E1 siRNA, and antioxidants (vitamins C and E). Further, we showed that DAS and vitamin C abrogated ethanol-mediated (50 mM) induction of CYP2E1 at 6 h, as well as production of ROS at 2 h, suggesting the role of oxidative stress in ethanol-mediated induction of CYP2E1. We then investigated the role of the protein kinase C/c-Jun N-terminal kinase/specificity protein1 (PKC/JNK/SP1) pathway in oxidative stress-mediated CYP2E1 induction. Our results showed that staurosporine, a non-specific inhibitor of PKC, as well as specific PKCζ inhibitor and PKCζ siRNA, abolished ethanol-induced CYP2E1 expression. In addition, inhibitors of JNK (SP600125) and SP1 (mithramycin A) completely abrogated induction of CYP2E1 by ethanol in SVGA astrocytes. Subsequently, we showed that CYP2E1 is also responsible for ethanol-mediated oxidative stress and apoptotic cell death in U937 monocytic cell lines. Finally, our results showed that PKC/JNK/SP1 pathway is also involved in regulation of CYP2E1 in U937 cells. This study has clinical implications with respect to alcohol-associated neuroinflammatory toxicity among alcohol users.

Indexed as

Allyl CompoundsAnthracenesApoptosisAstrocytesCell Line, TumorCytochrome P-450 CYP2E1Cytochrome P-450 CYP2E1 InhibitorsEthanolGene Expression RegulationHumansMAP Kinase Kinase 4MonocytesOxidative StressPlicamycinProtein Kinase CReactive Oxygen SpeciesAllyl Compoundsallyl sulfideAnthracenesCytochrome P-450 CYP2E1Cytochrome P-450 CYP2E1 InhibitorsEthanolMAP Kinase Kinase 4mithramycin APlicamycinProtein Kinase CpyrazolanthroneReactive Oxygen SpeciesRNA, Small InterferingSp1 Transcription FactorStaurosporineSulfides

Identifiers

PMID23519123
PMCPMC3615729
OpenAlexW2035415222

What OpenQuestion holds

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LicenceCC BY
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.