Evidence map›Paper›PMID 18362892›Full record

ArticleOncogene2008

Hierarchical involvement of Bak, VDAC1 and Bax in cisplatin-induced cell death.

N Tajeddine, L Galluzzi, O Kepp, E Hangen, E Morselli, L Senovilla, N Araujo, G Pinna, N Larochette, N Zamzami and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
6.1field-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

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.

  1. Pooled it
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  18. The role of Bcl-2 proteins in modulating neuronal CaBiochimica et biophysica acta. Molecular cell research · 2021
    Review
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  20. Review

33 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

13 authors at 4 institutions in 1 country.

N TajeddineINSERM, U848, Villejuif, France.
L Galluzzi
O Kepp
E Hangen
E Morselli
L Senovilla
N Araujo
G Pinna
N Larochette
N Zamzami
N Modjtahedi
A Harel-Bellan
G Kroemer
Université Paris-Sud · FRInserm · FRInstitut Gustave Roussy · FRCentre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Following the screening of a battery of distinct small-interfering RNAs that target various components of the apoptotic machinery, we found that knockdown of the voltage-dependent anion channel 1 (VDAC1) was particularly efficient in preventing cell death induced by cisplatin (CDDP) in non-small cell lung cancer cells. Both the downregulation of VDAC1 and its chemical inhibition with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid reduced the apoptosis-associated modifications induced by CDDP, including mitochondrial transmembrane potential dissipation and plasma membrane permeabilization. VDAC1 inhibition strongly reduced the CDDP-induced conformational activation of Bax, yet had no discernible effect on the activation of Bak, suggesting that VDAC1 acts downstream of Bak and upstream of Bax. Accordingly, knockdown of Bak abolished the activation of Bax, whereas Bax downregulation had no effect on Bak activation. In VDAC1-depleted cells, the failure of CDDP to activate Bax could be reversed by means of the Bcl-2/Bcl-X(L) antagonist ABT-737, which concomitantly restored CDDP cytotoxicity. Altogether, these results delineate a novel pathway for the induction of mitochondrial membrane permeabilization (MMP) in the course of CDDP-induced cell death that involves a hierarchical contribution of Bak, VDAC1 and Bax. Moreover, our data suggest that VDAC1 may act as a facultative regulator/effector of MMP, depending on the initial cytotoxic event.

Indexed as

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAntineoplastic AgentsApoptosisbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinBiphenyl CompoundsCell DeathCell Membrane PermeabilityCisplatinDrug SynergismHCT116 CellsHeLa CellsHumansModels, BiologicalNitrophenolsPiperazines4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidABT-737Antineoplastic AgentsBAK1 protein, humanBAX protein, humanbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinBiphenyl CompoundsCisplatinNitrophenolsPiperazinesSulfonamidesVDAC1 protein, humanVoltage-Dependent Anion Channel 1

Identifiers

PMID18362892
OpenAlexW2025291080

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.