Quercetin Stimulates NGF-induced Neurite Outgrowth in PC12 Cells via Activation of Na+/K+/2Cl- Cotransporter

Quercetin Stimulates NGF-induced Neurite Outgrowth in PC12 Cells via Activation of Na+/K+/2Cl- Cotransporter
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DOI:
10.1159/000331723
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发表时间:
2011-01-01
影响因子:
--
通讯作者:
Marunaka, Yoshinori
Marunaka, Yoshinori
中科院分区:
医学1区
文献类型:
--
作者:
Nakajima, Ken-ichi;Niisato, Naomi;Marunaka, Yoshinori

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我们最近报道了Na+/K+/2Cl(-)协同转运体亚型1(NKCC 1)在神经生长因子(NGF)诱导的PC 12 D细胞突起生长中起重要作用。另一方面,据报道,膳食黄酮类化合物,如槲皮素,芹菜素和木犀草素,刺激各种离子转运蛋白。在本报告中,我们研究了槲皮素,类黄酮,对神经生长因子诱导的神经突起生长在PC 12细胞(PC 12 D细胞的亲本株)的影响。槲皮素刺激神经生长因子诱导的神经突起生长的剂量依赖性的方式。通过RNAi方法敲低NKCC 1消除了类黄酮的刺激作用。槲皮素刺激NKCC 1活性(测量为布美他尼敏感的Rb-86流入),而NKCC 1蛋白的表达水平没有任何增加。槲皮素对神经突起生长的刺激作用依赖于细胞外Cl-。这些观察结果表明,槲皮素刺激神经生长因子诱导的神经突起的生长,通过增加Cl-掺入到细胞内的空间,通过激活NKCC 1在PC 12细胞。版权所有(C)2011 S. Karger AG,巴塞尔
We have recently reported that Na+/K+/2Cl(-) cotransporter isoform 1 (NKCC1) plays an essential role in nerve growth factor (NGF)-induced neurite outgrowth in PC12D cells. On the other hand, it has been reported that dietary flavonoids, such as quercetin, apigenin, and luteolin, stimulate various ion transporters. In the present report, we investigated the effect of quercetin, a flavonoid, on NGF-induced neurite outgrowth in PC12 cells (the parental strain of PC12D cells). Quercetin stimulated the NGF-induced neurite outgrowth in a dose-dependent manner. Knockdown of NKCC1 by RNAi methods abolished the stimulatory effect of flavonoid. Quercetin stimulated NKCC1 activity (measured as bumetanide-sensitive Rb-86 influx) without any increase in the expression level of NKCC1 protein. The stimulatory effect of quercetin on neurite outgrowth was dependent upon extracellular Cl-. These observations indicate that quercetin stimulates the NGF-induced neurite outgrowth via an increase in Cl- incorporation into the intracellular space by activating NKCC1 in PC12 cell. Copyright (C) 2011 S. Karger AG, Basel