論文 - 詳細
| RRC ID | 72200 |
|---|---|
| 著者 | Cheng A, Wang YF, Shinoda Y, Kawahata I, Yamamoto T, Jia WB, Yamamoto H, Mizobata T, Kawata Y, Fukunaga K. |
| タイトル | Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress. |
| ジャーナル | Acta Pharmacol Sin |
| Abstract |
We previously show that fatty acid-binding protein 3 (FABP3) triggers α-synuclein (Syn) accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model. But the role of fatty acid-binding protein 7 (FABP7) in the brain remains unclear. In this study we investigated whether FABP7 was involved in synucleinopathies. We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells, and treatment with arachidonic acid (100 M) significantly promoted FABP7-induced Syn aggregation, which was associated with cell death. We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with Kd value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid (ANS) assay; ligand 6 improved U251 cell survival via disrupting the FABP7-Syn interaction. We showed that activation of phospholipase A2 (PLA2) by psychosine (10 M) triggered oligomerization of endogenous Syn and FABP7, and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells (OPCs). FABP7 ligand 6 (1 M) significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death. This study demonstrates that FABP7 triggers α-synuclein oligomerization through oxidative stress, while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation, thereby rescuing glial cells and oligodendrocytes from cell death. |
| 巻・号 | 43(3) |
| ページ | 552-562 |
| 公開日 | 2022-3-1 |
| DOI | 10.1038/s41401-021-00675-8 |
| PII | 10.1038/s41401-021-00675-8 |
| PMID | 33935286 |
| PMC | PMC8888578 |
| MeSH | Animals Arachidonic Acid / pharmacology Cell Death / physiology Fatty Acid-Binding Protein 7 / metabolism* Humans Male Mice Mice, Inbred C57BL Neuroglia / metabolism* Oligodendrocyte Precursor Cells / drug effects Oligodendroglia / metabolism* Oxidative Stress / physiology* Phospholipases A2 / drug effects Protein Binding / physiology Psychosine / pharmacology alpha-Synuclein / metabolism* |
| IF | 5.064 |
| 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 | 6 |
| 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 | KG-1-C(RCB0270) |