Bumetanide-induced NKCC1 inhibition attenuates oxygen-glucose deprivation-induced decrease in proliferative activity and cell cycle progression arrest in cultured OPCs via p-38 MAPKs
Bumetanide-induced NKCC1 inhibition attenuates oxygen-glucose deprivation-induced decrease in proliferative activity and cell cycle progression arrest in cultured OPCs via p-38 MAPKs
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布美他尼诱导的 NKCC1 抑制可通过 p-38 MAPK 减弱氧-葡萄糖剥夺诱导的培养 OPC 中增殖活性的降低和细胞周期进展停滞
DOI：
10.1016/j.brainres.2015.04.006
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发表时间：
2015-07-10
期刊：
影响因子：
2.9
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Fu, Peicai;Tang, Ronghua;Wang, Wei
Na-K-Cl共转运蛋白1(NKCC1，阳离子-氯离子共转运蛋白家族的成员)介导了Na+和/或K+与Cl-在细胞质膜上的耦合运动(Haas和ForBush，2000，Annu)。Physiol牧师，62,515-534；Russell，2000，Physiol。Rev.，80,211-276)。尽管它是细胞体积、分泌的重要调节器，也是细胞凋亡和增殖的调节器(Chen等人，2005，J.ereb.血流学，25，54-66；Kahle等，2008，NAT。克莱恩。普赖特。Neurol，4,490-503；Kidokoro等人，2014，AmJ.Physiol.任。PhysIOL.，306，F1155-F1160；Wang等，2011，Cell.物理。生物化学，28,703-714)，NKCC1的S对少突胶质前体细胞(OPC)的作用尚未被表征。本研究的目的是研究抑制NKCC1是否以及在多大程度上改变氧糖剥夺(OGD)诱导的细胞周期进程。在本研究中，我们证明了用布美他尼抑制NKCC1可以减轻OGD诱导的OPC DNA合成的减少。Western blotting结果显示，抑制NKCC1使OGD处理细胞中细胞周期蛋白D1、CDK4和细胞周期蛋白E的表达增加。此外，我们的结果显示，布美他尼可通过P-38MAPK信号转导通路减弱OGD诱导的细胞增殖减少和细胞周期进程的停滞。因此，NKCC1在OGD诱导的应激下OPC的增殖中起着重要作用。(C)2015 Elsevier B.V.保留所有权利。
The Na-K-Cl co-transporter 1 (NKCC1; a member of the cation-chloride co-transporter family) mediates the coupled movement of Na+ and/or K+ with Cl- across the plasma membrane of cells (Haas and Forbush, 2000, Annu. Rev. Physiol., 62, 515-534; Russell, 2000, Physiol. Rev., 80, 211-276). Although it acts as an important regulator of cell volume, secretion, and modulator of cell apoptosis and proliferation (Chen et al., 2005,J. Cereb. Blood Flow Metab., 25, 54-66; Kahle et al., 2008, Nat. Clin. Pract. Neurol., 4, 490-503; Kidokoro et al., 2014, Am. J. Physiol. Ren. Physiol., 306, F1155-F1160; Wang et al., 2011, Cell. Physiol. Biochem., 28, 703-714), NKCC1's effects on oligodendrocyte precursor cells (OPCs) have not been characterized. The aim of this study was to investigate whether and to what extent inhibition of NKCC1 alters oxygen glucose deprivation (OGD)-induced cell cycle progression. In the present study, we demonstrated that inhibition of NKCC1 with bumetanide attenuates the decrease in OGD-induced DNA synthesis in cultured OPCs. Western blots showed that NKCC1 inhibition led to an increased expression of cyclin D1, CDK 4, and cyclin E in OGD-treated cells. Furthermore, our results showed bumetanide attenuated the decrease in OGD-induced proliferation and arrest of cell cycle progression via the P-38 MAPK signaling cascade. Thus, NKCC1 plays important roles in the proliferation of OPCs under OGD-induced stress.(C) 2015 Elsevier B.V. All rights reserved.