Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo.

Autor:	Frøyset AK; Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway., Edson AJ; Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway., Gharbi N; Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway., Khan EA; Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway., Dondorp D; Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway., Bai Q; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA., Tiraboschi E; Neural Circuits and Behaviour Group, Uni Research AS, Bergen N-5020, Norway., Suster ML; Neural Circuits and Behaviour Group, Uni Research AS, Bergen N-5020, Norway., Connolly JB; Waters Corporation, Wilmslow, Manchester, UK., Burton EA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA., Fladmark KE; Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway. Electronic address: kari.fladmark@uib.no.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2018 Jun; Vol. 16, pp. 237-247. Date of Electronic Publication: 2018 Feb 17.
DOI:	10.1016/j.redox.2018.02.010
Abstrakt:	DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP + , a mitochondrial complex I inhibitor shown to induce dopaminergic cells death. In a global label-free proteomics analysis of wild type and transgenic larvae exposed to MPP + , 3418 proteins were identified, in which 366 proteins were differentially regulated. In particular, we identified enzymes belonging to primary metabolism to be among proteins affected by MPP + in wild type animals, but not affected in the transgenic line. Moreover, by performing protein profiling on isolated astrocytes we showed that an increase in astrocytic DJ-1 expression up-regulated a large group of proteins associated with redox regulation, inflammation and mitochondrial respiration. The majority of these proteins have also been shown to be regulated by Nrf2. These findings provide a mechanistic insight into the protective role of astroglial up-regulation of DJ-1 and show that our transgenic zebrafish line with astrocytic DJ-1 over-expression can serve as a useful animal model to understand astrocyte-regulated neuroprotection associated with oxidative stress-related neurodegenerative disease. (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu