Evidence map›Paper›PMID 25052090›Full record

ArticleJournal of cell science2014

PARP1-mediated necrosis is dependent on parallel JNK and Ca²⁺/calpain pathways.

Diana L Douglas, Christopher P Baines

Open access · greenAbstract read
In one paragraph

Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Melittin inhibits MPPThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. ATR prevents CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Regulatory role of calpain in neuronal death.Neural regeneration research · 2018
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  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

2 authors at 1 institution in 1 country.

Diana L DouglasDalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri, 65211, USA.
Christopher P BainesDalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri, 65211, USA Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri, 65211, USA Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri, 65211, USA bainesc@missouri.edu.
University of Missouri · US

Funding

Molecular Identity of the Cardiac Mitochondrial PoreR01HL094404 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI BAINES, CHRISTOPHER P · 2009 to 2018
$3.6M
Identifying novel components of the cardiac necrotic programR21HL092327 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI BAINES, CHRISTOPHER P · 2008 to 2009
$412k
NHLBI NIH HHS HL092327NHLBI NIH HHS HL094404NHLBI NIH HHS R01 HL094404NHLBI NIH HHS R21 HL092327
6 · The paper itself

Abstract

Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme that can trigger caspase-independent necrosis. Two main mechanisms for this have been proposed: one involving RIP1 and JNK kinases and mitochondrial permeability transition (MPT), the other involving calpain-mediated activation of Bax and mitochondrial release of apoptosis-inducing factor (AIF). However, whether these two mechanisms represent distinct pathways for PARP1-induced necrosis, or whether they are simply different components of the same pathway has yet to be tested. Mouse embryonic fibroblasts (MEFs) were treated with either N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or β-Lapachone, resulting in PARP1-dependent necrosis. This was associated with increases in calpain activity, JNK activation and AIF translocation. JNK inhibition significantly reduced MNNG- and β-Lapachone-induced JNK activation, AIF translocation, and necrosis, but not calpain activation. In contrast, inhibition of calpain either by Ca(2+) chelation or knockdown attenuated necrosis, but did not affect JNK activation or AIF translocation. To our surprise, genetic and/or pharmacological inhibition of RIP1, AIF, Bax and the MPT pore failed to abrogate MNNG- and β-Lapachone-induced necrosis. In conclusion, although JNK and calpain both contribute to PARP1-induced necrosis, they do so via parallel mechanisms.

Indexed as

MAP Kinase Signaling System3T3 CellsAnimalsApoptosisCalpainCell Culture TechniquesCell DeathMiceMitochondriaNecrosisPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesRNA, Small InterferingSignal TransductionCalpainParp1 protein, mousePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesRNA, Small InterferingAIFCalpainCell deathJNKMitochondriaNecrosisPARP1

Identifiers

PMID25052090
PMCPMC4179488
OpenAlexW2161657577

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.