Evidence map›Paper›PMID 20332089›Full record

ArticleThe Journal of biological chemistry2010

Rapid activation of glutamate cysteine ligase following oxidative stress.

Cecile M Krejsa, Christopher C Franklin, Collin C White, Jeffrey A Ledbetter, Gary L Schieven, Terrance J Kavanagh

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.5field-weighted citation impact, top 6% 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

59 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
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  13. Review
  14. AntenatalInternational journal of molecular sciences · 2024
    Article
  15. The Hepatoprotective Effects ofPlants (Basel, Switzerland) · 2023
    Review
  16. Review
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  20. Article
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 3 institutions in 1 country.

Cecile M KrejsaDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195, USA.
Christopher C Franklin
Collin C White
Jeffrey A Ledbetter
Gary L Schieven
Terrance J Kavanagh
University of Washington · USBristol-Myers Squibb (United States) · USUniversity of Colorado Denver · US

Funding

WILDLIFE BIOMARKER APPLICATIONS TO REMEDIATION DECISION MAKINGP42ES004696 · NIEHS · UNIVERSITY OF WASHINGTON · PI GALLAGHER, EVAN P · 1987 to 2021
$51.2M
XENOBIOTIC BIOTRANSFORMATION AND DISPOSITIONP30ES007033 · NIEHS · UNIVERSITY OF WASHINGTON · PI ALI SHOJAIE · 1995 to 2026
$42.5M
SPECIFICITY OF OXYGEN DNA DAMAGE AND MUTAGENESISP01AG001751 · NIA · UNIVERSITY OF WASHINGTON · PI RABINOVITCH, PETER S · 1985 to 2021
$29.6M
Environmetal Pathology/Toxicology Training ProgramT32ES007032 · NIEHS · UNIVERSITY OF WASHINGTON · PI FAUSTMAN, ELAINE M, ROSENFELD, MICHAEL E · 1985 to 2023
$10.7M
Regulation of Glutathione Biosynthesis during apoptosisR01CA090473 · NCI · UNIVERSITY OF WASHINGTON · PI FRANKLIN, CHRISTOPHER · 2002 to 2005
$1.0M
Glutamate-L-cysteine ligase expression and liver injuryR01ES010849 · NIEHS · UNIVERSITY OF WASHINGTON · PI KAVANAGH, TERRANCE J · 2002 to 2004
$783k
NCI NIH HHS R01 CA090473NCI NIH HHS R01CA90473NIA NIH HHS P01 AG001751NIA NIH HHS P01AG01751NIEHS NIH HHS P30 ES007033NIEHS NIH HHS P30ES07033NIEHS NIH HHS P42 ES004696NIEHS NIH HHS P42ES04696NIEHS NIH HHS R01 ES010849NIEHS NIH HHS R01ES10849NIEHS NIH HHS T32 ES007032NIEHS NIH HHS T32ES07032
6 · The paper itself

Abstract

Glutamate cysteine ligase (GCL) catalyzes the rate-limiting step in the formation of the cellular antioxidant glutathione (GSH). The GCL holoenzyme consists of two separately coded proteins, a catalytic subunit (GCLC) and a modifier subunit (GCLM). Both GCLC and GLCM are controlled transcriptionally by a variety of cellular stimuli, including oxidative stress. This study addresses post-translational control of GCL activity, which increased rapidly in human lymphocytes following oxidative stress. Activation of GCL occurred within minutes of treatment and without any change in GCL protein levels and coincided with an increase in the proportion of GCLC in the holoenzyme form. Likewise, GCLM shifted from the monomeric form to holoenzyme and higher molecular weight species. Normal rat tissues also showed a distribution of monomeric and higher molecular weight forms. Neither GCL activation, nor the formation of holoenzyme, required a covalent intermolecular disulfide bridge between GCLC and GCLM. However, in immunoprecipitation studies, a neutralizing epitope associated with enzymatic activity was protected following cellular oxidative stress. Thus, the N-terminal portion of GCLC may undergo a change that stabilizes the GCL holoenzyme. Our results suggest that a dynamic equilibrium exists between low and high activity forms of GCL and is altered by transient oxidative stress. This provides a mechanism for the rapid post-translational activation of GCL and maintenance of cellular GSH homeostasis.

Indexed as

AnimalsDisulfidesEnzyme ActivationGlutamate-Cysteine LigaseGlutathioneHoloenzymesHomeostasisHumansJurkat CellsLymphocytesMiceOrgan SpecificityOxidative StressProtein Structure, TertiaryRatsTranscription, GeneticDisulfidesGCLC protein, ratGCLM protein, humanGlutamate-Cysteine LigaseGlutathioneHoloenzymes

Identifiers

PMID20332089
PMCPMC2871480
OpenAlexW2009863034

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.