Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis
Show others and affiliations
2017 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 20, p. 4028-4041Article in journal (Refereed) Published
Abstract [en]

DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease.

Place, publisher, year, edition, pages
Oxford University Press, 2017. Vol. 26, no 20, p. 4028-4041
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-140877DOI: 10.1093/hmg/ddx294ISI: 000412427100013PubMedID: 29016861OAI: oai:DiVA.org:umu-140877DiVA, id: diva2:1158427
Note

Correction: Dominik Piston, Lydia Alvarez-Erviti, Vikas Bansal, Daniela Gargano, Zhi Yao, Gyorgy Szabadkai, Mark Odell, M Rhyan Puno, Benny Björkblom, Jodi Maple-Grødem, Peter Breuer, Oliver Kaut, Jan Petter Larsen, Stefan Bonn, Simon Geir Møller, Ullrich Wüllner, Anthony H V Schapira, Matthew E Gegg. DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis. Human Molecular Genetics. Volume 27, Issue 3, 1 February 2018, Pages 576. DOI: 10.1093/hmg/ddx425

Available from: 2017-11-20 Created: 2017-11-20 Last updated: 2018-03-02Bibliographically approved

Open Access in DiVA

fulltext(978 kB)15 downloads
File information
File name FULLTEXT01.pdfFile size 978 kBChecksum SHA-512
b72aa22bb3465f3fd0155a9e0cc497a3fefaeaf480971c0aadf4d96c4a1350de1218b18e3d4df3e24ba14a3b6c9af2aed549be803c9f57536c86b559bb8bf1f9
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Björkblom, Benny
By organisation
Department of Chemistry
In the same journal
Human Molecular Genetics
Cell and Molecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar
Total: 15 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 143 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf