Evidence map›Paper›PMID 24434817›Full record

ArticleAutophagy2014

Glutathione transferase mu 2 protects glioblastoma cells against aminochrome toxicity by preventing autophagy and lysosome dysfunction.

Sandro Huenchuguala, Patricia Muñoz, Patricio Zavala, Mónica Villa, Carlos Cuevas, Ulises Ahumada, Rebecca Graumann, Beston F Nore, Eduardo Couve, Bengt Mannervik and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
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

45 citing papers in PubMed, 69 citations in OpenAlex.

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  5. Neuromelanin-induced cellular stress and neurotoxicity in the pathogenesis of Parkinson's disease.Apoptosis : an international journal on programmed cell death · 2025
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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

12 authors at 6 institutions in 6 countries.

Sandro HuenchugualaMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
Patricia MuñozMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
Patricio ZavalaMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
Mónica VillaMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
Carlos CuevasMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
Ulises AhumadaMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
Rebecca GraumannMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
Beston F NoreLaboratory of Medicine; Clinical Research Center-Novum; Karolinska Institutet; Sweden; Department of Medical Biochemistry; School of Medicine; Faculty of Medical Sciences; University of Sulaimani; Ministry of Higher Education and Research; Kurdistan Regional Government; Iraq.
Eduardo CouveDepartment of Biology and Environmental sciences; University of Valparaiso; Valparaiso, Chile.
Bengt MannervikDepartment of Neurochemistry; Stockholm University; Stockholm, Sweden.
Irmgard ParisMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile; Department of Basic Sciences; Santo Tomas University; Viña del Mar, Chile.
Juan Segura-AguilarMolecular and Clinical Pharmacology; ICBM-Instituto de Ciencias Biomédicas; Faculty of Medicine; University of Chile; Santiago, Chile.
University of Chile · CLMolecular Medicine Ireland · IEFaculty (United Kingdom) · GBKarolinska Institutet · SEStockholm University · SEValparaiso University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

U373MG cells constitutively express glutathione S-transferase mu 2 (GSTM2) and exhibit (3)H-dopamine uptake, which is inhibited by 2 µM of nomifensine and 15 µM of estradiol. We generated a stable cell line (U373MGsiGST6) expressing an siRNA against GSTM2 that resulted in low GSTM2 expression (26% of wild-type U373MG cells). A significant increase in cell death was observed when U373MGsiGST6 cells were incubated with 50 µM purified aminochrome (18-fold increase) compared with wild-type cells. The incubation of U373MGsiGST6 cells with 75 µM aminochrome resulted in the formation of autophagic vacuoles containing undigested cellular components, as determined using transmission electron microscopy. A significant increase in autophagosomes was determined by measuring endogenous LC3-II, a significant decrease in cell death was observed in the presence of bafilomycin A 1, and a significant increase in cell death was observed in the presence of trehalose. A significant increase in LAMP2 immunostaining was observed, a significant decrease in bright red fluorescence of lysosomes with acridine orange was observed, and bafilomycin A 1 pretreatment reduced the loss of lysosome acidity. A significant increase in cell death was observed in the presence of lysosomal protease inhibitors. Aggregation of TUBA/α-tubulin (tubulin, α) and SQSTM1 protein accumulation were also observed. Moreover, a significant increase in the number of lipids droplets was observed compared with U373MG cells with normal expression of GSTM2. These results support the notion that GSTM2 is a protective enzyme against aminochrome toxicity in astrocytes and that aminochrome cell death in U373MGsiGST6 cells involves autophagic-lysosomal dysfunction.

Indexed as

AstrocytesAutophagyCell LineGlioblastomaGlutathione TransferaseHumansIndolequinonesLysosomesMitochondriaProtective Agentsaminochrome 1glutathione S-transferase Mu 2Glutathione TransferaseIndolequinonesProtective Agentsaminochromeastrocytesautophagydopamineglutathione transferaselysosome dysfunctionParkinson diseasesiRNA

Identifiers

PMID24434817
PMCPMC4091149
OpenAlexW1965024373

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.