Evidence map›Paper›PMID 24607566›Full record

ArticleBiochimica et biophysica acta2014

Modulation of calcium-induced cell death in human neural stem cells by the novel peptidylarginine deiminase-AIF pathway.

Kin Pong U, Venkataraman Subramanian, Antony P Nicholas, Paul R Thompson, Patrizia Ferretti

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

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

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  17. Deimination, Intermediate Filaments and Associated Proteins.International journal of molecular sciences · 2020
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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

5 authors at 3 institutions in 2 countries.

Kin Pong UDevelopmental Biology Unit, UCL Institute of Child Health, London WC1N 1EH, UK.
Venkataraman SubramanianDepartment of Chemistry, TSRI, Scripps Florida, FL 33458, USA.
Antony P NicholasDepartment of Neurology, University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, AL 35294, USA.
Paul R ThompsonDepartment of Chemistry, TSRI, Scripps Florida, FL 33458, USA.
Patrizia FerrettiDevelopmental Biology Unit, UCL Institute of Child Health, London WC1N 1EH, UK. Electronic address: p.ferretti@ucl.ac.uk.
Scripps Research Institute · USUniversity College London · GBUniversity of Alabama at Birmingham · US

Funding

Haloacetamidine based inactivators of Protein Arginine Deiminase 4R01GM079357 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI THOMPSON, PAUL R · 2007 to 2016
$3.3M
Biotechnology and Biological Sciences Research Council BB/D013755/1Medical Research Council G0700089Medical Research Council G070089Medical Research Council MC_PC_15004NIGMS NIH HHS GM079357NIGMS NIH HHS R01 GM079357Wellcome Trust GR082557
6 · The paper itself

Abstract

PADs (peptidylarginine deiminases) are calcium-dependent enzymes that change protein-bound arginine to citrulline (citrullination/deimination) affecting protein conformation and function. PAD up-regulation following chick spinal cord injury has been linked to extensive tissue damage and loss of regenerative capability. Having found that human neural stem cells (hNSCs) expressed PAD2 and PAD3, we studied PAD function in these cells and investigated PAD3 as a potential target for neuroprotection by mimicking calcium-induced secondary injury responses. We show that PAD3, rather than PAD2 is a modulator of cell growth/death and that PAD activity is not associated with caspase-3-dependent cell death, but is required for AIF (apoptosis inducing factor)-mediated apoptosis. PAD inhibition prevents association of PAD3 with AIF and AIF cleavage required for its translocation to the nucleus. Finally, PAD inhibition also hinders calcium-induced cytoskeleton disassembly and association of PAD3 with vimentin, that we show to be associated also with AIF; together this suggests that PAD-dependent cytoskeleton disassembly may play a role in AIF translocation to the nucleus. This is the first study highlighting a role of PAD activity in balancing hNSC survival/death, identifying PAD3 as an important upstream regulator of calcium-induced apoptosis, which could be targeted to reduce neural loss, and shedding light on the mechanisms involved.

Indexed as

Gene Expression Regulation, DevelopmentalApoptosisApoptosis Inducing FactorBlotting, WesternCalciumCell NucleusCell ProliferationHumansHydrolasesImmunoenzyme TechniquesImmunoprecipitationIn Situ HybridizationNeural Stem CellsProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 2Real-Time Polymerase Chain ReactionAIFM1 protein, humanApoptosis Inducing FactorCalciumHydrolasesPADI2 protein, humanProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 2RNA, MessengerRNA, Small InterferingApoptosis inducing factor (AIF)Cell deathCitrullination–deiminationHuman neural stem cellPeptidylarginine deiminase (PAD, PADI)Vimentin

Identifiers

PMID24607566
PMCPMC3996523
OpenAlexW2172339454

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.