Evidence map›Paper›PMID 29148034›Full record

ArticleBritish journal of pharmacology2018

Role of p62/SQSTM1 beyond autophagy: a lesson learned from drug-induced toxicity in vitro.

Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

22 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  8. The sequestosome 1 protein: therapeutic vulnerabilities in ovarian cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Chlamydia trachomatis induces autophagy by p62 in HeLa cell.World journal of microbiology & biotechnology · 2021
    Article
  15. Article
  16. Role of autophagy in alcohol and drug-induced liver injury.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. A Systems Toxicology Approach for the Prediction of Kidney Toxicity and Its Mechanisms In Vitro.Toxicological sciences : an official journal of the Society of Toxicology · 2019
    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

7 authors at 1 institution in 1 country.

Fernando AlegreDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
Ángela B MoragregaDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
Miriam PoloDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
Alberto Marti-RodrigoDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.ORCID 0000-0003-4390-7692
Juan V EspluguesDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.ORCID 0000-0001-8205-021X
Ana Blas-GarciaDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.ORCID 0000-0001-7870-1470
Nadezda ApostolovaDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.ORCID 0000-0002-4487-2471
Universitat de València · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeSQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Its altered function has been associated with different human pathologies, such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood. EXPERIMENTAL APPROACH: We evaluated the expression of p62 in cultured Hep3B cells and their derived ρ° cells (lacking mitochondria), along with markers of autophagy and mitochondrial dysfunction. The effects of efavirenz were compared with those of known pharmacological stressors, rotenone, thapsigargin and CCCP, and we also used transient silencing with siRNA and p62 overexpression. Western blotting, quantRT-PCR and fluorescence microscopy were used to assay these effects and their underlying mechanisms. KEY

resultsIn Hep3B cells, efavirenz augmented p62 protein content, an effect not observed in the corresponding ρ° cells. p62 up-regulation followed enhanced SQSTM1 expression mediated through the transcription factor CHOP/DDIT3, while other well-known regulators (NF-kB and Nrf2) were not involved. Inhibition of autophagy with 3MA or with transient silencing of Atg5 did not affect SQSTM1 expression in efavirenz-treated cells while p62 overexpression ameliorated the deleterious effect of efavirenz on cell viability. CONCLUSION AND IMPLICATIONS: In our model, p62 exerted a specific, autophagy-independent role and protected against efavirenz-induced mitochondrial ROS generation and activation of the NLRP3 inflammasome. These findings add to the multifunctional nature of p62 and may help to understand the off-target effects of clinically useful drugs.

Indexed as

AlkynesAutophagyBenzoxazinesCell Line, TumorCyclopropanesDose-Response Relationship, DrugHepatocytesHumansReactive Oxygen SpeciesReverse Transcriptase InhibitorsSequestosome-1 ProteinAlkynesBenzoxazinesCyclopropanesefavirenzReactive Oxygen SpeciesReverse Transcriptase InhibitorsSequestosome-1 ProteinSQSTM1 protein, human

Identifiers

PMID29148034
PMCPMC5773949
OpenAlexW2769629281

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.