論文 - 詳細
| RRC ID | 17679 |
|---|---|
| 著者 | Mori A, Yamashita S, Uchino K, Suga T, Ikeda T, Takamatsu K, Ishizaki M, Koide T, Kimura E, Mita S, Maeda Y, Hirano T, Uchino M. |
| タイトル | Derlin-1 overexpression ameliorates mutant SOD1-induced endoplasmic reticulum stress by reducing mutant SOD1 accumulation. |
| ジャーナル | Neurochem Int |
| Abstract |
Unfolded protein responses, including induction of stress sensor kinases, chaperones, and apoptotic mediators, are involved in the familial amyotrophic lateral sclerosis (ALS) model related to mutant Cu/Zn superoxide dismutase (SOD1) and sporadic ALS. We hypothesized that the endoplasmic reticulum-resident factor Derlin-1 plays a pivotal role in the regulation of misfolded proteins evoked by mutant SOD1. We show that Derlin-1 overexpression reduced mutant SOD1-induced cell toxicity and increased cell viability by suppressing the activation of the ER stress pathway factors: immunoglobulin-binding protein, activating transcription factor 6 p50, and C/EBP homologous protein. Interestingly, exogenous Derlin-1 resulted in a decrease in the amount of mutant SOD1, and a lesser decrease in that of wild-type SOD1, in transfected cells. Reduced SOD1 protein expression was observed in the microsomal fraction of wild-type and mutant SOD1 cells. Our results indicate that Derlin-1 regulates the turn over of SOD1 by promoting the proteasomal and autophagosomal degradation of SOD1 protein, but not by decreasing mutant SOD1 mRNA levels. Insights into the effects of Derlin-1 on mutant SOD1 may facilitate advancements in the treatment of motor neuron degeneration associated with ALS. |
| 巻・号 | 58(3) |
| ページ | 344-53 |
| 公開日 | 2011-2-1 |
| DOI | 10.1016/j.neuint.2010.12.010 |
| PII | S0197-0186(10)00380-3 |
| PMID | 21185345 |
| MeSH | Amyotrophic Lateral Sclerosis / enzymology Amyotrophic Lateral Sclerosis / genetics Amyotrophic Lateral Sclerosis / metabolism* Animals Autophagy / genetics Cell Line, Tumor Down-Regulation / genetics Endoplasmic Reticulum / enzymology Endoplasmic Reticulum / metabolism* Humans Membrane Proteins / biosynthesis* Membrane Proteins / genetics Mice Mutation / physiology Neurons / enzymology Neurons / metabolism* Proteasome Endopeptidase Complex / metabolism RNA, Messenger / biosynthesis Stress, Physiological / genetics* Superoxide Dismutase / antagonists & inhibitors Superoxide Dismutase / genetics* Superoxide Dismutase / metabolism Superoxide Dismutase-1 |
| IF | 3.881 |
| 引用数 | 21 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY NEUROSCIENCES |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | |
| ヒト・動物細胞 | NB2a(RCB2639) |