論文 - 詳細
| RRC ID | 58803 |
|---|---|
| 著者 | Abe Y, Honsho M, Kawaguchi R, Matsuzaki T, Ichiki Y, Fujitani M, Fujiwara K, Hirokane M, Oku M, Sakai Y, Yamashita T, Fujiki Y. |
| タイトル | A peroxisome deficiency-induced reductive cytosol state up-regulates the brain-derived neurotrophic factor pathway. |
| ジャーナル | J Biol Chem |
| Abstract |
The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function. |
| 巻・号 | 295(16) |
| ページ | 5321-5334 |
| 公開日 | 2020-4-17 |
| DOI | 10.1074/jbc.RA119.011989 |
| PII | S0021-9258(17)48552-8 |
| PMID | 32165495 |
| PMC | PMC7170515 |
| MeSH | Animals Astrocytes / metabolism* Brain-Derived Neurotrophic Factor / metabolism* CHO Cells Cell Line Cell Line, Tumor Cells, Cultured Cricetinae Cricetulus Cytosol / metabolism Fatty Acids / metabolism Hippocampus / cytology Humans Neurons / metabolism* Oxidation-Reduction Peroxisomal Disorders / metabolism* Peroxisomes / metabolism* Plasmalogens / metabolism Rats Rats, Wistar Up-Regulation |
| IF | 4.238 |
| 引用数 | 1 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | RCR-1 |