Search: id:"swepub:oai:DiVA.org:umu-140877" >
DJ-1 is a redox sen...
DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis
-
Piston, Dominik (author)
-
Alvarez-Erviti, Lydia (author)
-
Bansal, Vikas (author)
-
show more...
-
Gargano, Daniela (author)
-
Yao, Zhi (author)
-
Szabadkai, Gyorgy (author)
-
Odell, Mark (author)
-
Puno, M. Rhyan (author)
-
- Björkblom, Benny (author)
- Umeå universitet,Kemiska institutionen
-
Maple-Grodem, Jodi (author)
-
Breuer, Peter (author)
-
Kaut, Oliver (author)
-
Larsen, Jan Petter (author)
-
Bonn, Stefan (author)
-
Moller, Simon Geir (author)
-
Wuellner, Ullrich (author)
-
Schapira, Anthony H. V. (author)
-
Gegg, Matthew E. (author)
-
show less...
-
(creator_code:org_t)
- 2017-07-25
- 2017
- English.
-
In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 26:20, s. 4028-4041
- Related links:
-
https://umu.diva-por... (primary) (Raw object)
-
show more...
-
https://academic.oup...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Piston, Dominik
-
Alvarez-Erviti, ...
-
Bansal, Vikas
-
Gargano, Daniela
-
Yao, Zhi
-
Szabadkai, Gyorg ...
-
show more...
-
Odell, Mark
-
Puno, M. Rhyan
-
Björkblom, Benny
-
Maple-Grodem, Jo ...
-
Breuer, Peter
-
Kaut, Oliver
-
Larsen, Jan Pett ...
-
Bonn, Stefan
-
Moller, Simon Ge ...
-
Wuellner, Ullric ...
-
Schapira, Anthon ...
-
Gegg, Matthew E.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Cell and Molecul ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Medical Biotechn ...
-
and Medical Biotechn ...
- Articles in the publication
-
Human Molecular ...
- By the university
-
Umeå University