Zinc causes loss of membrane potential and elevates reactive oxygen species in rat brain mitochondria
Zinc causes loss of membrane potential and elevates reactive oxygen species in rat brain mitochondria
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DOI：
10.1016/j.mito.2004.11.001
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发表时间：
2005-02-01
期刊：
影响因子：
4.4
通讯作者：
Reynolds, IJ
中科院分区：
文献类型：
--
作者：
Dineley, KE;Richards, LL;Reynolds, IJ
新出现的证据表明，Zn 2+可能会损害神经元代谢。我们研究了Zn 2+如何影响以谷氨酸+苹果酸，琥珀酸或甘油3-磷酸为燃料的离体脑线粒体的活性。亚微摩尔水平的Zn 2+耗散膜电位和抑制氧利用率在所有三个基板条件。Zn 2+诱导的去极化被膜不渗透的金属螯合剂EGTA逆转，并被单向转运体阻断抑制。环孢菌素A不阻断Zn ~（2+）诱导的去极化。在谷氨酸+苹果酸或甘油3-磷酸条件下，添加Zn 2+增加活性氧（ROS）的积累，但抑制琥珀酸支持的ROS积累。这些结果表明，在所有生理相关的底物条件下，Zn 2+都会阻断线粒体功能。(C)2004年Elsevier B. V.和线粒体研究学会。All rights reserved.
Emerging evidence suggests that Zn2+ may impair neuronal metabolism. We examined how Zn2+ affects the activity of isolated brain mitochondria fueled with glutamate + malate, succinate or glycerol 3-phosphate. Submicromolar levels of Zn2+ dissipated membrane potential and inhibited oxygen utilization in all three substrate conditions. Zn2+-induced depolarization was reversed by the membrane-impermeant metal chelator, EGTA, and was inhibited by uniporter blockade. Cyclosporin A did not block Zn2+-induced depolarization. Added Zn2+ increased accumulation of reactive oxygen species (ROS) in glutamate + malate or glycerol 3-phosphate conditions, but inhibited succinate-supported ROS accumulation. These results show that Zn2+ blocks mitochondrial function in all physiologically relevant substrate conditions. (C) 2004 Elsevier B.V. and Mitochondria Research Society. All rights reserved.