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首页> 外文期刊>Cellular Physiology and Biochemistry >K-Cl ~-cotransporter 1 (KCC1) negatively regulates NGF-induced neurite outgrowth in PC12 cells
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K-Cl ~-cotransporter 1 (KCC1) negatively regulates NGF-induced neurite outgrowth in PC12 cells

机译：K-Cl〜-共转运蛋白1（KCC1）负调节PC12细胞中NGF诱导的神经突增生。

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摘要

Potassium chloride cotransporters (KCCs) mediate electroneutrally-coupled transport of K ~+ and Cl ~-, and play crucial roles in various cell functions including regulation of cell volume and homeostasis of cellular Cl ~-content. Four isoforms of KCCs (KCC1, 2, 3, and 4) have been identified. KCC1 is ubiquitously expressed, whereas KCC2 is mainly expressed in neuronal cells of central nervous system. KCC3 is highly expressed in heart, skeletal muscle, kidney, lung and placenta. KCC4 is mainly expressed in epithelial cells. In this study, we investigated roles of KCCs in NGF-induced neurite outgrowth of rat pheochromocytoma PC12 cells. The most abundantly expressed isoform in PC12 cells was KCC1. Inhibition of KCCs using [(dihydronindenyl)oxy] alkanoic acid (DIOA), an inhibitor of KCCs, enhanced the NGF-induced neurite outgrowth of PC12 cells in a dose-dependent manner. Treatment of PC12 cells with NGF significantly decreased mRNA expression of KCC1, whereas other isoforms, KCC2-4, showed no changes in their mRNA expression in response to NGF treatment. Knockdown of KCC1 using small interfering RNA (siRNA) enhanced the NGF-induced neurite outgrowth. These results suggest that KCC1 negatively regulates the NGF-induced neurite outgrowth of PC12 cells.
机译：氯化钾共转运蛋白（KCC）介导K〜+和Cl〜-的电子中性耦合转运，并在各种细胞功能中发挥关键作用，包括调节细胞体积和细胞Cl〜含量的稳态。已鉴定出四种KCC同种型（KCC1、2、3和4）。 KCC1普遍存在，而KCC2主要在中枢神经系统的神经元细胞中表达。 KCC3在心脏，骨骼肌，肾脏，肺和胎盘中高表达。 KCC4主要在上皮细胞中表达。在这项研究中，我们调查了KCC在NGF诱导的大鼠嗜铬细胞瘤PC12细胞神经突生长中的作用。 PC12细胞中表达最丰富的同工型是KCC1。使用[（二氢茚基）氧基]链烷酸（DIOA）抑制KCC，以剂量依赖的方式增强了NGF诱导的PC12细胞神经突生长。用NGF处理PC12细胞会显着降低KCC1的mRNA表达，而其他同工型KCC2-4则不会响应NGF处理而显示其mRNA表达变化。使用小干扰RNA（siRNA）抑制KCC1增强了NGF诱导的神经突增生。这些结果表明，KCC1负调节NGF诱导的PC12细胞的神经突生长。

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