Activation of ATP-sensitive potassium channels enhances DMT1-mediated iron uptake in SK-N-SH cells in vitro.
Activation of ATP-sensitive potassium channels enhances DMT1-mediated iron uptake in SK-N-SH cells in vitro.
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体外 ATP 敏感钾通道的激活增强 SK-N-SH 细胞中 DMT1 介导的铁摄取
DOI：
10.1038/srep33674
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发表时间：
2016-09-20
影响因子：
4.6
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Du X;Xu H;Shi L;Jiang Z;Song N;Jiang H;Xie J
铁转运蛋白二价金属转运蛋白1（DMT 1）在帕金森病（PD）患者体内铁的蓄积中起重要作用。膜超极化是影响其铁转运功能的因素之一。除了铁，ATP敏感性钾（KATP）通道的选择性激活也有助于在PD多巴胺能神经元的脆弱性。有趣的是，KATP通道的激活可诱导膜超极化。因此，研究KATP通道激活对DMT 1介导的铁摄取功能的影响具有重要意义。在本研究中，二氮嗪激活KATP通道导致SK-N-SH细胞膜电位超极化，并增加DMT 1介导的铁摄取。这导致细胞内铁水平增加，随后线粒体膜电位降低，ROS产生增加。在HEK 293细胞上，膜片钳记录到二氮嗪对Fe ~（2+）诱发电流的延迟失活，证明二氮嗪可延长DMT 1介导的铁转运。格列本脲抑制KATP通道可阻断亚铁离子内流及细胞损伤。Kir6.2/SUR 1的过表达导致铁内流和细胞内铁水平的增加，在二氮嗪处理后显著增加。
Iron importer divalent metal transporter 1 (DMT1) plays a crucial role in the nigal iron accumulation in Parkinson’s disease (PD). Membrane hyperpolarization is one of the factors that could affect its iron transport function. Besides iron, selective activation of the ATP-sensitive potassium (KATP) channels also contributes to the vulnerability of dopaminergic neurons in PD. Interestingly, activation of KATP channels could induce membrane hyperpolarization. Therefore, it is of vital importance to study the effects of activation of KATP channels on DMT1-mediated iron uptake function. In the present study, activation of KATP channels by diazoxide resulted in the hyperpolarization of the membrane potential and increased DMT1-mediated iron uptake in SK-N-SH cells. This led to an increase in intracellular iron levels and a subsequent decrease in the mitochondrial membrane potential and an increase in ROS production. Delayed inactivation of the Fe2+-evoked currents by diazoxide was recorded by patch clamp in HEK293 cells, which demonstrated that diazoxide could prolonged DMT1-facilitated iron transport. While inhibition of KATP channels by glibenclamide could block ferrous iron influx and the subsequent cell damage. Overexpression of Kir6.2/SUR1 resulted in an increase in iron influx and intracellular iron levels, which was markedly increased after diazoxide treatment.
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影响因子：
25
作者：
Schiemann, Julia;Schlaudraff, Falk;Klose, Verena;Bingmer, Markus;Seino, Susumu;Magill, Peter J.;Zaghloul, Kareem A.;Schneider, Gaby;Liss, Birgit;Roeper, Jochen
通讯作者：
Roeper, Jochen
影响因子：
4.5
作者：
Mackenzie, B;Ujwal, ML;Hediger, MA
通讯作者：
Hediger, MA
影响因子：
25
作者：
Liss, B;Haeckel, O;Roeper, J
通讯作者：
Roeper, J
影响因子：
16.2
作者：
Schernhammer E;Hansen J;Rugbjerg K;Wermuth L;Ritz B
通讯作者：
Ritz B
6-羟基多巴胺中毒时二价金属转运蛋白 1 的上调依赖于 IRE/IRP。
影响因子：
44.1
作者：
Jiang, Hong;Song, Ning;Xie, Junxia
通讯作者：
Xie, Junxia