Evidence map›Paper›PMID 31760358›Full record

ArticleRedox biology2020

A functionalized hydroxydopamine quinone links thiol modification to neuronal cell death.

Ali Farzam, Karan Chohan, Miroslava Strmiskova, Sarah J Hewitt, David S Park, John P Pezacki, Dennis Özcelik

Open access · goldAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 29 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Ali FarzamDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie Private, Ottawa, ON, K1N 6N5, Canada.
Karan ChohanDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Miroslava StrmiskovaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie Private, Ottawa, ON, K1N 6N5, Canada.
Sarah J HewittUniversity of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
David S ParkUniversity of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
John P PezackiDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie Private, Ottawa, ON, K1N 6N5, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Dennis ÖzcelikDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie Private, Ottawa, ON, K1N 6N5, Canada. Electronic address: dennis.ozcelik@sund.ku.dk.
University of Ottawa · CAuOttawa Brain and Mind Research Institute

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent findings suggest that dopamine oxidation contributes to the development of Parkinson's disease (PD); however, the mechanistic details remain elusive. Here, we compare 6-hydroxydopamine (6-OHDA), a product of dopamine oxidation that commonly induces dopaminergic neurodegeneration in laboratory animals, with a synthetic alkyne-functionalized 6-OHDA variant. This synthetic molecule provides insights into the reactivity of quinone and neuromelanin formation. Employing Huisgen cycloaddition chemistry (or "click chemistry") and fluorescence imaging, we found that reactive 6-OHDA p-quinones cause widespread protein modification in isolated proteins, lysates and cells. We identified cysteine thiols as the target site and investigated the impact of proteome modification by quinones on cell viability. Mass spectrometry following cycloaddition chemistry produced a large number of 6-OHDA modified targets including proteins involved in redox regulation. Functional in vitro assays demonstrated that 6-OHDA inactivates protein disulfide isomerase (PDI), which is a central player in protein folding and redox homeostasis. Our study links dopamine oxidation to protein modification and protein folding in dopaminergic neurons and the PD model.

Indexed as

AnimalsCell LineCell SurvivalCycloaddition ReactionCysteineDisease Models, AnimalDopaminergic NeuronsDown-RegulationFemaleHumansHydroxydopaminesMaleMass SpectrometryMiceOxidopamineParkinson DiseaseCysteineHydroxydopaminesOxidopamineProtein Disulfide-IsomerasesSulfhydryl Compounds6-Hydroxydopamine p-quinoneDopamine oxidationNeurotoxicityParkinson's diseasePost-translational protein modificationProtein disulfide isomerase

Identifiers

PMID31760358
PMCPMC6880099
OpenAlexW2989383108

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.