Evidence map›Paper›PMID 21427056›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2011

Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.

Irmgard Paris, Patricia Muñoz, Sandro Huenchuguala, Eduardo Couve, Laurie H Sanders, John Timothy Greenamyre, Pablo Caviedes, Juan Segura-Aguilar

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Article
  3. Rab12 is a regulator of mitophagy and mitochondrial homeostasis.bioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Review
  6. Neuromelanin-induced cellular stress and neurotoxicity in the pathogenesis of Parkinson's disease.Apoptosis : an international journal on programmed cell death · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  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

8 authors at 4 institutions in 2 countries.

Irmgard ParisProgram of Molecular and Clinical Pharmacology, Biomedical Science Institute, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
Patricia Muñoz
Sandro Huenchuguala
Eduardo Couve
Laurie H Sanders
John Timothy Greenamyre
Pablo Caviedes
Juan Segura-Aguilar
University of Chile · CLInstitute for Neurodegenerative Disorders · USUniversity of Pittsburgh · USUniversity of Valparaíso · CL

Funding

Stress Proteins and Neuroprotection Against Parkinsonian Cell DeathP01NS059806 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GREENAMYRE, J TIMOTHY · 2009 to 2013
$6.3M
DNA Damage and Repair in Parkinsons DiseaseF32ES019008 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SANDERS, LAURIE H · 2010 to 2011
$61k
NIEHS NIH HHS 1F32ES019008-01NINDS NIH HHS NS059806
6 · The paper itself

Abstract

Aminochrome, the precursor of neuromelanin, has been proposed to be involved in the neurodegeneration neuromelanin-containing dopaminergic neurons in Parkinson's disease. We aimed to study the mechanism of aminochrome-dependent cell death in a cell line derived from rat substantia nigra. We found that aminochrome (50μM), in the presence of NAD(P)H-quinone oxidoreductase, EC 1.6.99.2 (DT)-diaphorase inhibitor dicoumarol (DIC) (100μM), induces significant cell death (62 ± 3%; p < 0.01), increase in caspase-3 activation (p < 0.001), release of cytochrome C, disruption of mitochondrial membrane potential (p < 0.01), damage of mitochondrial DNA, damage of mitochondria determined with transmission electron microscopy, a dramatic morphological change characterized as cell shrinkage, and significant increase in number of autophagic vacuoles. To determine the role of autophagy on aminochrome-induced cell death, we incubated the cells in the presence of vinblastine and rapamycin. Interestingly, 10μM vinblastine induces a 5.9-fold (p < 0.001) and twofold (p < 0.01) significant increase in cell death when the cells were incubated with 30μM aminochrome in the absence and presence of DIC, respectively, whereas 10μM rapamycin preincubated 24 h before addition of 50μM aminochrome in the absence and the presence of 100μM DIC induces a significant decrease (p < 0.001) in cell death. In conclusion, autophagy seems to be an important protective mechanism against two different aminochrome-induced cell deaths that initially showed apoptotic features. The cell death induced by aminochrome when DT-diaphorase is inhibited requires activation of mitochondrial pathway, whereas the cell death induced by aminochrome alone requires inhibition of autophagy-dependent degrading of damaged organelles and recycling through lysosomes.

Indexed as

AnimalsAutophagyCaspase 3Cell DeathCell LineCytochromes cDNA, MitochondrialIndolequinonesMelaninsMembrane Potential, MitochondrialMicroscopy, Electron, TransmissionMitochondriaNAD(P)H Dehydrogenase (Quinone)Nerve DegenerationRatsSirolimusaminochrome 1Casp3 protein, ratCaspase 3Cytochromes cDNA, MitochondrialIndolequinonesMelaninsNAD(P)H Dehydrogenase (Quinone)neuromelaninSirolimusVinblastine

Identifiers

PMID21427056
PMCPMC3145404
OpenAlexW2107720385

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.