Evidence map›Paper›PMID 10947971›Full record

ArticleThe Biochemical journal2000

Multidrug resistance protein MRP1 protects against the toxicity of the major lipid peroxidation product 4-hydroxynonenal.

J Renes, E E de Vries, G J Hooiveld, I Krikken, P L Jansen, M Müller

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

Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.8field-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

24 citing papers in PubMed, 114 citations in OpenAlex.

  1. Regulation of P-Glycoprotein during Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024
    Review
  2. Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer's Disease?International journal of molecular sciences · 2022
    Review
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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 at 2 institutions in 1 country.

J RenesDivision of Gastroenterology and Hepatology, Groningen University Institute for Drug Exploration (GUIDE), University Hospital Groningen, NL-9700 RB Groningen, The Netherlands.
E E de Vries
G J Hooiveld
I Krikken
P L Jansen
M Müller
University of Groningen · NLUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

4-Hydroxynonenal (4HNE) is the most prevalent toxic lipid peroxidation product formed during oxidative stress. It exerts its cytotoxicity mainly by the modification of intracellular proteins. The detection of 4HNE-modified proteins in several degenerative disorders suggests a role for 4HNE in the onset of these diseases. Efficient protection mechanisms are required to prevent the intracellular accumulation of 4HNE. The toxicity of 4HNE was tested with the small cell lung cancer cell lines GLC(4) and the multidrug-resistance-protein (MRP1)-overexpressing counterpart GLC(4)/Adr. In the presence of the MRP1 inhibitor MK571 or the GSH-depleting agent buthionine sulphoximine, both cell lines became more sensitive and showed decreased survival. Transport experiments were performed with the (3)H-labelled glutathione S-conjugate of 4HNE ([(3)H]GS-4HNE) with membrane vesicles from GLC(4)-derived cell lines with different expression levels of MRP1. [(3)H]GS-4HNE was taken up in an ATP-dependent manner and the transport rate was dependent on the amount of MRP1. The MRP1 inhibitor MK571 decreased [(3)H]GS-4HNE uptake. MRP1-specific [(3)H]GS-4HNE transport was demonstrated with membrane vesicles from High Five insect cells overexpressing recombinant MRP1. Kinetic experiments showed an apparent K(m) of 1.6+/-0.21 microM (mean+/-S.D.) for MRP1-mediated [(3)H]GS-4HNE transport. In conclusion, MRP1 has a role in the protection against 4HNE toxicity and GS-4HNE is a novel MRP1 substrate. MRP1, together with GSH, is hypothesized to have a role in the defence against oxidative stress.

Indexed as

Lipid PeroxidationAdenosine TriphosphateAldehydesAnimalsATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1Biological TransportButhionine SulfoximineCarcinoma, Small CellCell LineCell SurvivalCysteine Proteinase InhibitorsDose-Response Relationship, DrugEnzyme InhibitorsGlutathione4-hydroxy-2-nonenalAdenosine TriphosphateAldehydesATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1Buthionine SulfoximineCysteine Proteinase InhibitorsEnzyme InhibitorsGlutathioneLeukotriene AntagonistsPropionatesQuinolinesRecombinant Proteinsverlukast

Identifiers

PMID10947971
PMCPMC1221284
OpenAlexW2078476328

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.