Amyloid-β promotes calcium influx and neurodegeneration via stimulation of L voltage-sensitive calcium channels rather than NMDA channels in cultured neurons
Amyloid-β promotes calcium influx and neurodegeneration via stimulation of L voltage-sensitive calcium channels rather than NMDA channels in cultured neurons
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DOI：
10.3233/jad-2001-3507
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发表时间：
2001-01-01
影响因子：
4
通讯作者：
Shea, Thomas B.
中科院分区：
文献类型：
--
作者：
Ho, Rebecca;Ortiz, Daniela;Shea, Thomas B.
将培养的神经元和神经元细胞暴露于聚集的淀粉样蛋白-β（A β）诱导多种神经变性事件，包括细胞溶质钙的积累、活性氧物质的产生、微管相关蛋白tau的异常磷酸化水平和细胞凋亡。防止钙在胞质溶胶内蓄积也可防止所有其他事件，表明钙蓄积是A β神经毒性的早期和关键事件。钙内流已被认为是通过L电压敏感性钙通道或NMDA通道发生的。钙流入分化的人神经母细胞瘤细胞以前已归因于L电压敏感性钙通道，但NMDA通道的贡献没有检查。在本研究中，用NMDA通道拮抗剂MK-801处理这些细胞，未能减弱A β诱导的钙内流或神经变性，而L电压敏感性钙通道拮抗剂尼莫地定阻断A β诱导的钙内流。我们的研究结果表明，在这些急性细胞培养分析中，NMDA通道对A β神经毒性没有显著影响。
Exposure of cultured neurons and neuronal cells to aggregated amyloid-beta (A beta) induces multiple neurodegenerative events including accumulation of cytosolic calcium, generation of reactive oxygen species, abnormal levels of phosphorylation of the microtubule-associated protein tau, and apoptosis. Prevention of accumulation of calcium within the cytosol also prevents all other events, suggesting that calcium accumulation is an early and pivotal event in A beta neurotoxicity. Calcium influx has been suggested to occur via L voltage-sensitive calcium channels or NMDA channels. Calcium influx into differentiated human neuroblastoma cells has been previously attributed to the L voltage-sensitive calcium channel, but the contribution of the NMDA channel was not examined. In the present study, treatment of these cells with MK-801, an antagonist of NMDA channels, failed to attenuate A beta-induced calcium influx or neurodegeneration, while nimopridine, an antagonist of the L voltage-sensitive calcium channel, blocked A beta-induced calcium influx. Our findings suggest that NMDA channels do not contribute significantly to A beta neurotoxicity in these acute cell culture analyses.