論文 - 詳細
| RRC ID | 53237 |
|---|---|
| 著者 | Johnson WM, Golczak M, Choe K, Curran PL, Miller OG, Yao C, Wang W, Lin J, Milkovic NM, Ray A, Ravindranath V, Zhu X, Wilson MA, Wilson-Delfosse AL, Chen SG, Mieyal JJ. |
| タイトル | Regulation of DJ-1 by Glutaredoxin 1 in Vivo: Implications for Parkinson's Disease. |
| ジャーナル | Biochemistry |
| Abstract |
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, caused by the degeneration of the dopaminergic neurons in the substantia nigra. Mutations in PARK7 (DJ-1) result in early onset autosomal recessive PD, and oxidative modification of DJ-1 has been reported to regulate the protective activity of DJ-1 in vitro. Glutathionylation is a prevalent redox modification of proteins resulting from the disulfide adduction of the glutathione moiety to a reactive cysteine-SH, and glutathionylation of specific proteins has been implicated in regulation of cell viability. Glutaredoxin 1 (Grx1) is the principal deglutathionylating enzyme within cells, and it has been reported to mediate protection of dopaminergic neurons in Caenorhabditis elegans; however many of the functional downstream targets of Grx1 in vivo remain unknown. Previously, DJ-1 protein content was shown to decrease concomitantly with diminution of Grx1 protein content in cell culture of model neurons (SH-SY5Y and Neuro-2A lines). In the current study we aimed to investigate the regulation of DJ-1 by Grx1 in vivo and characterize its glutathionylation in vitro. Here, with Grx(-/-) mice we provide show that Grx1 regulates protein levels of DJ-1 in vivo. Furthermore, with model neuronal cells (SH-SY5Y) we observed decreased DJ-1 protein content in response to treatment with known glutathionylating agents, and with isolated DJ-1 we identified two distinct sites of glutathionylation. Finally, we found that overexpression of DJ-1 in the dopaminergic neurons partly compensates for the loss of the Grx1 homologue in a C. elegans in vivo model of PD. Therefore, our results reveal a novel redox modification of DJ-1 and suggest a novel regulatory mechanism for DJ-1 content in vivo. |
| 巻・号 | 55(32) |
| ページ | 4519-32 |
| 公開日 | 2016-8-16 |
| DOI | 10.1021/acs.biochem.5b01132 |
| PMID | 26894491 |
| PMC | PMC4987251 |
| MeSH | Amino Acid Sequence Animals Caenorhabditis elegans Cell Line, Tumor Cysteine / metabolism Glutaredoxins / metabolism* Glutathione / metabolism Humans Mice Parkinson Disease / metabolism* Protein Deglycase DJ-1 / chemistry Protein Deglycase DJ-1 / deficiency Protein Deglycase DJ-1 / metabolism* Protein Processing, Post-Translational |
| IF | 2.865 |
| 引用数 | 16 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1346 tm4634 |