Evidence map›Paper›PMID 23640457›Full record

ArticleCell death & disease2013

ATM-NFκB axis-driven TIGAR regulates sensitivity of glioma cells to radiomimetics in the presence of TNFα.

S Sinha, R Ghildiyal, V S Mehta, E Sen

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
7.3field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  7. The role of TIGAR in nervous system diseases.Frontiers in aging neuroscience · 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

4 authors at 2 institutions in 1 country.

S SinhaCellular and Molecular Neuroscience Division, National Brain Research Centre, Manesar, Haryana, India.
R Ghildiyal
V S Mehta
E Sen
National Brain Research Centre · INParas Hospitals · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gliomas are resistant to radiation therapy, as well as to TNFα induced killing. Radiation-induced TNFα triggers Nuclear factor κB (NFκB)-mediated radioresistance. As inhibition of NFκB activation sensitizes glioma cells to TNFα-induced apoptosis, we investigated whether TNFα modulates the responsiveness of glioma cells to ionizing radiation-mimetic Neocarzinostatin (NCS). TNFα enhanced the ability of NCS to induce glioma cell apoptosis. NCS-mediated death involved caspase-9 activation, reduction of mitochondrial copy number and lactate production. Death was concurrent with NFκB, Akt and Erk activation. Abrogation of Akt and NFκB activation further potentiated the death inducing ability of NCS in TNFα cotreated cells. NCS-induced p53 expression was accompanied by increase in TP53-induced glycolysis and apoptosis regulator (TIGAR) levels and ATM phosphorylation. siRNA-mediated knockdown of TIGAR abrogated NCS-induced apoptosis. While DN-IκB abrogated NCS-induced TIGAR both in the presence and absence of TNFα, TIGAR had no effect on NFκB activation. Transfection with TIGAR mutant (i) decreased apoptosis and γH2AX foci formation (ii) decreased p53 (iii) elevated ROS and (iv) increased Akt/Erk activation in cells cotreated with NCS and TNFα. Heightened TIGAR expression was observed in GBM tumors. While NCS induced ATM phosphorylation in a NFκB independent manner, ATM inhibition abrogated TIGAR and NFκB activation. Metabolic gene profiling indicated that TNFα affects NCS-mediated regulation of several genes associated with glycolysis. The existence of ATM-NFκB axis that regulate metabolic modeler TIGAR to overcome prosurvival response in NCS and TNFα cotreated cells, suggests mechanisms through which inflammation could affect resistance and adaptation to radiomimetics despite concurrent induction of death.

Indexed as

Adenosine TriphosphateAntibiotics, AntineoplasticApoptosisApoptosis Regulatory ProteinsAtaxia Telangiectasia Mutated ProteinsBrain NeoplasmsCaspase 9Cell Cycle ProteinsCell Line, TumorDNA-Binding ProteinsGliomaGlycolysisHumansIntracellular Signaling Peptides and ProteinsLactic AcidMicrotubule-Associated ProteinsAdenosine TriphosphateAntibiotics, AntineoplasticApoptosis Regulatory ProteinsAtaxia Telangiectasia Mutated ProteinsATM protein, humanCaspase 9Cell Cycle ProteinsDNA-Binding ProteinsIntracellular Signaling Peptides and ProteinsLactic AcidMAP1LC3A protein, humanMicrotubule-Associated ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NF-kappa BPhosphoric Monoester HydrolasesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesRNA, Small InterferingTIGAR protein, humanTumor Necrosis Factor-alphaTumor Suppressor Protein p53Tumor Suppressor ProteinsZinostatin

Identifiers

PMID23640457
PMCPMC3674344
OpenAlexW2027825753

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.