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首页> 外文期刊>Journal of Cellular Physiology >Amyloid-beta-induced reactive oxygen species production and priming are differentially regulated by ion channels in microglia.
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Amyloid-beta-induced reactive oxygen species production and priming are differentially regulated by ion channels in microglia.

机译：Amyloid-beta-induced活性氧生产和启动是不同的由小胶质细胞的离子通道。

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Production of reactive oxygen species (ROS) by microglial cells and subsequent oxidative stress are strongly implicated in the pathogenesis of Alzheimer's disease. Although it is recognized that amyloid-beta (Abeta) plays a major role in inducing and regulating microglial ROS production in Alzheimer's disease, to date little is known about cellular mechanisms underlying Abeta-stimulated ROS production. Here, we identified ion channels involved in Abeta-induced microglial ROS production and in Abeta-induced microglial priming. Acute stimulation of microglial cells with either fibrillar Abeta(1-42) (fAbeta(1-42) ) or soluble Abeta(1-42) (sAbeta(1-42) ) caused significant increases in microglial ROS production, which were abolished by inhibition of TRPV1 cation channels with 5-iodo-resiniferatoxin (I-RTX), but were unaffected by inhibition of K(+) channels with charybdotoxin (CTX). Furthermore, pretreatment with either fAbeta(1-42) or sAbeta(1-42) induced microglial priming, that is, increased ROS production upon secondary stimulation with the phorbol ester PMA. Microglial priming induced by fAbeta(1-42) or sAbeta(1-42) remained unaffected by TRPV1 channel inhibition with I-RTX. However, sAbeta(1-42) -induced priming was inhibited by CTX and margatoxin, but not by TRAM-34 or paxilline, indicating a role of Kv1.3 voltage-gated K(+) channels, but not of Ca(2+) -activated K(+) channels, in the priming process. In summary, our data suggest that in microglia Abeta-induced ROS production and priming are differentially regulated by ion channels, and that TRPV1 cation channels and Kv1.3 K(+) channels may provide potential therapeutic targets to reduce microglia-induced oxidative stress in Alzheimer's disease.
机译：生产活性氧(ROS)小胶质细胞和随后的氧化应激强烈的发病机制涉及阿尔茨海默氏症。淀粉样β蛋白(β淀粉状蛋白质)过程中起着重要作用诱导和调节小胶质ROS生产在阿尔茨海默病,迄今所知甚少关于细胞的机制Abeta-stimulated ROS生产。确定离子通道参与Abeta-induced生产和在Abeta-induced小胶质ROS小胶质启动。小胶质细胞与纤维β淀粉状蛋白质(1-42)(fAbeta(1-42))或可溶性β淀粉状蛋白质(1-42)(sAbeta(1-42))引起显著增加小胶质ROS生产被抑制废除TRPV1阳离子渠道与5-iodo-resiniferatoxin (I-RTX),但是被抑制的影响K(+)渠道charybdotoxin (CTX)。预处理与fAbeta(1-42)或sAbeta(1-42)诱导小胶质启动,也就是说,ROS增加生产在次要的与佛波醇酯PMA刺激。引起小胶质启动fAbeta(1-42)或sAbeta(1-42)仍然不受TRPV1通道与I-RTX抑制。全身的启动由CTX和抑制margatoxin,但不是通过TRAM-34或paxilline,指示Kv1.3电压门控的角色K (+)渠道,但不是Ca(2 +)激活K (+)渠道,在启动过程中。数据显示,在小胶质细胞Abeta-induced ROS生产和启动是不同的由离子通道,TRPV1阳离子渠道和Kv1.3 K(+)可以提供渠道减少潜在的治疗目标microglia-induced氧化应激在阿尔茨海默氏症疾病。

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