論文 - 詳細
| RRC ID | 54717 |
|---|---|
| 著者 | Nishizaki T. |
| タイトル | Fe3+ Facilitates Endocytic Internalization of Extracellular Aβ1-42 and Enhances Aβ1-42-Induced Caspase-3/Caspase-4 Activation and Neuronal Cell Death. |
| ジャーナル | Mol Neurobiol |
| Abstract |
Amyloid β (Aβ) peptide is a critical causative factor in Alzheimer's disease (AD) and of a variety of fragmented Aβ peptides Aβ1-42 thought to exhibit the most neurotoxic effect. The present study investigated the effects of Fe3+ on Aβ1-42 internalization and Aβ1-42-induced caspase activation and neurotoxicity using mouse hippocampal slices and cultured PC-12 cells. Extracellularly applied Aβ1-42 increased the cell-associated Aβ1-42 levels in a concentration-dependent manner, and the effect was enhanced by adding Fe3+. Fe3+-induced enhancement of the cell-associated Aβ1-42 levels was significantly inhibited by the endocytosis inhibitors dynasore and methyl-β-cyclodextrin. Aβ1-42 reduced PC-12 cell viability in a concentration-dependent manner, and further reduction of the cell viability was obtained with Fe3+. Aβ1-42-induced reduction of cell viability was not affected by A187, an antagonist of amylin-3 receptor. Aβ1-42 activated caspase-3, caspase-4, and caspase-8 to a variety of degrees and Fe3+ further enhanced Aβ1-42-induced activation of caspase-3 and caspase-4. Taken together, these results indicate that Fe3+ accelerates endocytic internalization of extracellular Aβ1-42, enhances Aβ1-42-induced caspase-3/caspase-4 activation, and promotes Aβ1-42-induced neuronal cell death, regardless of amylin receptor. |
| 巻・号 | 56(7) |
| ページ | 4812-4819 |
| 公開日 | 2019-7-1 |
| DOI | 10.1007/s12035-018-1408-y |
| PII | 10.1007/s12035-018-1408-y |
| PMID | 30402707 |
| MeSH | Amyloid beta-Peptides / pharmacology* Animals Caspase 3 / metabolism* Caspases Caspases, Initiator Cell Death / drug effects Endocytosis* / drug effects Enzyme Activation / drug effects Extracellular Space / chemistry* Iron / pharmacology* Male Mice, Inbred C57BL Neurons / drug effects Neurons / metabolism Neurons / pathology* PC12 Cells Peptide Fragments / pharmacology* Rats |
| IF | 4.586 |
| 引用数 | 2 |
| 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 | News |
| 各媒体での言及数の合計 | 1 |
| 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 | PC-12(RCB0009) |