β-Amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: implications for Alzheimer's disease
β-Amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: implications for Alzheimer's disease
复制标题
β-淀粉样肽衍生的氧依赖性自由基抑制培养星形胶质细胞中谷氨酸的摄取：对阿尔茨海默病的影响
DOI：
--
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
D. Butterfield
中科院分区：
文献类型：
--
作者：
M. Harris;J. Carney;P. Cole;K. Hensley;B. Howard;Laura J. Martin;P. Bummer;Yaning Wang;N. W. Pedigo;D. Butterfield
β-淀粉样蛋白（β-Amyloid，Aβ）是阿尔茨海默病（Alzheimer's disease，AD）脑内老年斑的主要成分，近年来发现A β可通过氧依赖机制产生自由基。采用电子顺磁共振（EPR）自旋捕集技术，以苯基-α-叔丁基硝酮（PBN）为自旋捕集剂，直接检测Aβ自由基。我们已经扩展了这些研究，以研究来自Aβ肽的氧自由基的性质，我们表明，这些自由基能够抑制培养的星形胶质细胞中谷氨酸的摄取。脑中星形胶质细胞谷氨酸摄取抑制的一个含义是细胞外谷氨酸水平增加，这对神经元是兴奋性毒性的。这些结果支持以下假设：AD中的Aβ神经毒性可能部分归因于Aβ衍生的氧依赖性自由基对谷氨酸摄取的抑制。
β-Amyloid (Aβ), the central constituent of senile plaques in Alzheimer's disease (AD) brains, was shown by us recently to generate free radicals in an oxygen dependent mechanism. Aβ-derived free radicals were detected directly using electron paramagnetic resonance (EPR) spin trapping techniques employing the spin trap phenyl-α-tert-butylnitrone (PBN). We have extended these studies to investigate the nature of the oxyradicals derived from Aβ peptides, and we show that these free radicals are able to inhibit glutamate uptake in cultured astrocytes. An implication of inhibited astrocyte glutamate uptake in brain is increased extracellular levels of glutamate, which is excitotoxic to neurons. These results support the hypothesis that Aβ neurotoxicity in AD may be due in part to Aβ-derived, oxygen-dependent free radical inhibition of glutamate uptake.