Evidence map›Paper›PMID 25009780›Full record

ReviewRedox biology2014

Redox status in mammalian cells and stem cells during culture in vitro: critical roles of Nrf2 and cystine transporter activity in the maintenance of redox balance.

Tetsuro Ishii, Giovanni E Mann

Open access · goldAbstract readReview
In one paragraph

Review in Redox biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

65 citing papers in PubMed, 131 citations in OpenAlex.

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  20. HO-1 Limits the Efficacy of Vemurafenib/PLX4032 in BRAFAntioxidants (Basel, Switzerland) · 2022
    Article

5 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

2 authors at 2 institutions in 2 countries.

Tetsuro IshiiUniversity of Tsukuba, Ibaraki, Japan.
Giovanni E MannCardiovascular Division, British Heart Foundation Centre of Research Excellence, School of Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.
British Heart Foundation · GBUniversity of Tsukuba · JP

Funding

British Heart Foundation FS / 10 / 59 / 28533British Heart Foundation FS/10/59/28533British Heart Foundation FS/13/66/30445British Heart Foundation PG / 13 / 1 / 29801British Heart Foundation PG/13/1/29801Wellcome Trust 059752
6 · The paper itself

Abstract

Culturing cells and tissues in vitro has provided valuable insights into the molecular mechanisms regulating redox signaling in cells with implications for medicine. However, standard culture techniques maintain mammalian cells in vitro under an artificial physicochemical environment such as ambient air and 5% CO2. Oxidative stress is caused by the rapid oxidation of cysteine to cystine in culture media catalyzed by transition metals, leading to diminished intracellular cysteine and glutathione (GSH) pools. Some cells, such as fibroblasts and macrophages, express cystine transport activity, designated as system [Formula: see text], which enables cells to maintain these pools to counteract oxidative stress. Additionally, many cells have the ability to activate the redox sensitive transcription factor Nrf2, a master regulator of cellular defenses against oxidative stress, and to upregulate xCT, the subunit of the [Formula: see text] transport system leading to increases in cellular GSH. In contrast, some cells, including lymphoid cells, embryonic stem cells and iPS cells, express relatively low levels of xCT and cannot maintain cellular cysteine and GSH pools. Thus, fibroblasts have been used as feeder cells for the latter cell types based on their ability to supply cysteine. Other key Nrf2 regulated gene products include heme oxygenase 1, peroxiredoxin 1 and sequestosome1. In macrophages, oxidized LDL activates Nrf2 and upregulates the scavenger receptor CD36 forming a positive feedback loop to facilitate removal of the oxidant from the vascular microenvironment. This review describes cell type specific responses to oxygen derived stress, and the key roles that activation of Nrf2 and membrane transport of cystine and cysteine play in the maintenance and proliferation of mammalian cells in culture.

Indexed as

Activating Transcription Factor 4Amino Acid Transport Systems, AcidicAnimalsCD36 AntigensCystineGlutathioneHumansLymphocytesNF-E2-Related Factor 2Oxidative StressStem CellsActivating Transcription Factor 4Amino Acid Transport Systems, AcidicCD36 AntigensCystineGlutathioneNF-E2-Related Factor 22-Mercaptoethanol4HNE, 4-hydroxynonenalBCS, bathocuproine sulfonateCD36Cystine transporterEmbryonic stem cellsES cells, embryonic stem cellsFeeder cellsGlutathioneHO-1, heme oxygenase 1iPS cellsiPS cells, induced pluripotent stem cellsKeap1, Kelch-like ECH-associated protein 1LymphocytesMRPs, multidrug resistance-associated proteinsNrf2Nrf2, nuclear factor erythroid 2-related factor 2oxLDL, oxidized low density lipoproteinOxygenPrx1, peroxiredoxin 1SQSTM1, sequestosome1xCT

Identifiers

PMID25009780
PMCPMC4085355
OpenAlexW2042288808

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.