PUBLICATION
Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo
- Authors
- Frøyset, A.K., Edson, A.J., Gharbi, N., Khan, E.A., Dondorp, D., Bai, Q., Tiraboschi, E., Suster, M.L., Connolly, J.B., Burton, E.A., Fladmark, K.E.
- ID
- ZDB-PUB-180312-2
- Date
- 2018
- Source
- Redox Biology 16: 237-247 (Journal)
- Registered Authors
- Burton, Edward A., Suster, Maximiliano
- Keywords
- Astrocyte, Cell survival, DJ-1, Oxidative stress, Parkinson's disease
- MeSH Terms
-
- Animals
- Animals, Genetically Modified/genetics
- Astrocytes/metabolism
- Astrocytes/pathology
- Disease Models, Animal
- Dopaminergic Neurons/metabolism
- Gene Expression Regulation, Enzymologic
- Humans
- Inflammation/genetics*
- Inflammation/pathology
- Larva/genetics
- Mitochondria/genetics
- Mitochondria/pathology
- NF-E2-Related Factor 2/genetics*
- NF-E2-Related Factor 2/metabolism
- Neuroprotective Agents/metabolism
- Oxidation-Reduction
- Oxidative Stress
- Parkinson Disease/genetics*
- Parkinson Disease/metabolism
- Parkinson Disease/pathology
- Protein Deglycase DJ-1/genetics*
- Protein Deglycase DJ-1/metabolism
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 29525604 Full text @ Redox Biol.
Citation
Frøyset, A.K., Edson, A.J., Gharbi, N., Khan, E.A., Dondorp, D., Bai, Q., Tiraboschi, E., Suster, M.L., Connolly, J.B., Burton, E.A., Fladmark, K.E. (2018) Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo. Redox Biology. 16:237-247.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping