Modulation of Na+ ,K+ pumping and neurotransmitter uptake by beta-amyloid
文献类型：期刊论文
| 作者 | Gu, QB; Zhao, JX; Fei, J; Schwarz, W |
| 刊名 | NEUROSCIENCE
 |
| 出版日期 | 2004 |
| 卷号 | 126期号:1页码:61-67 |
| 关键词 | Na+ glutamate transporter GABA transporter Alzheimer's disease Xenopus oocyte K+-ATPase |
| 通讯作者 | Schwarz, W (reprint author), Max Planck Inst Biophys, Marie Curie Str 15, Frankfurt, Germany.,schwarz@mpibp-frankfurt.mpg.de |
| 英文摘要 | Micromolar concentrations of beta-amyloid (Abeta), a 40/42-amino-acid-long proteolytic fragment (Abeta(1-40/42)) of the amyloid precursor protein, was shown previously to play a crucial role in pathogenesis of Alzheimer's disease. We used the Xenopus oocyte expression system to investigate specific effects of micromolar concentrations of Abeta(1-42) on the neurotransmitter transporters for gamma-aminobutyric acid (GABA), GAT1, and for the excitatory amino acid glutamate, EAAC1, which are driven by the transmembrane Na+ gradient that is regulated by the Na+,K+-ATPase. Brief treatment with Abeta(1-42), up to 80 min, leads to a significant inhibition of ion translocation by the Na+, K+-ATPase (30-40%); also glutamate uptake is inhibited (20%) while GABA uptake is not affected. Since reduced glutamate uptake will result in elevated, neurotoxic concentrations of extracellular glutamate, we investigated the effects of Abeta(1-42) and the smaller fragments, Abeta(12-28) and Abeta(25-35), on EAAC1 in more detail. Prolonged incubation in 1 muM Abeta(1-42) leads to further, strong inhibition of glutamate uptake and EAAC1-mediated current (after 4 h inhibition amounts to more than 80%). Abeta(12-28) is less effective with 50% inhibition after 4 h of incubation at 20 muM. Abeta(1-42) and Abeta(12-28) affect EAAC1-mediated current to a similar extent as the rate of glutamate uptake. The effects on EAAC1-mediated current are irreversible if Abeta were applied for longer time periods. Peptides directly microinjected into the oocyte are ineffective suggesting that the observed effect were mediated by extracellular proteins. Abeta(25-35) hardly affects EAAC1-mediated current or glutamate uptake. The results demonstrate that Abeta specifically inhibits the Na+,K+ pump and EAAC1. The domain between amino acids 12 and 28 of Abeta seems to play a crucial role for inhibition of EAAC1. The inhibition of EAAC1 by neurotoxic, elevated extracellular glutamate levels may contribute to Alzheimer's pathogenesis. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. |
| 学科主题 | Neurosciences & Neurology |
| 类目[WOS] | Neurosciences |
| 关键词[WOS] | NICOTINIC ACETYLCHOLINE-RECEPTORS ; ALZHEIMERS-DISEASE ; SODIUM-PUMP ; HIPPOCAMPAL-NEURONS ; XENOPUS OOCYTES ; EXTERNAL K+ ; PEPTIDE ; PROTEIN ; ATPASE ; PHOSPHORYLATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000221707100006 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2029]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Gu, QB,Zhao, JX,Fei, J,et al. Modulation of Na+ ,K+ pumping and neurotransmitter uptake by beta-amyloid[J]. NEUROSCIENCE,2004,126(1):61-67. |
| APA | Gu, QB,Zhao, JX,Fei, J,&Schwarz, W.(2004).Modulation of Na+ ,K+ pumping and neurotransmitter uptake by beta-amyloid.NEUROSCIENCE,126(1),61-67. |
| MLA | Gu, QB,et al."Modulation of Na+ ,K+ pumping and neurotransmitter uptake by beta-amyloid".NEUROSCIENCE 126.1(2004):61-67. |
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