Iron status and lipopolysaccharide regulate Ndfip1 by activation of nuclear factor-kappa B
Iron status and lipopolysaccharide regulate Ndfip1 by activation of nuclear factor-kappa B
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铁状态和脂多糖通过激活核因子 kappa B 调节 Ndfip1
DOI：
10.1007/s10534-013-9674-7
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发表时间：
2013-12-01
期刊：
影响因子：
3.5
通讯作者：
Xie, Junxia
中科院分区：
文献类型：
--
作者：
Xu, Huamin;Chang, Qing;Xie, Junxia
Nedd 4家族相互作用蛋白1（Ndfip 1）是泛素连接酶Nedd 4家族的衔接蛋白，其靶向蛋白进行降解。最近的研究证实了Ndfip 1作为铁代谢调节因子的作用，并指出Ndfip 1通过调节铁输入者二价金属转运蛋白1（DMT 1）的降解而参与铁的稳态。然而，人们对Ndfip 1是如何调控的知之甚少。本研究旨在探讨Ndfip 1的水平调控及其可能的机制。在这项研究中，我们研究了各种刺激，包括铁状态和脂多糖（LPS）对Ndfip 1在MES 23.5多巴胺能细胞系中表达的影响。结果表明，Ndfip 1在这些细胞中的表达增加亚铁超载，但不铁超载，铁剥夺后去铁胺降低。另外，LPS可显著增加Ndfip 1的表达。此外，我们证明了这些不同刺激对Ndfip 1表达的调节是通过激活核因子-κ B来实现的。我们推测铁状态和LPS可能通过激活核因子-κ B而导致Ndfip 1表达的变化。
Nedd4 family interacting protein 1 (Ndfip1) is an adaptor protein for the Nedd4 family of ubiquitin ligases that target proteins for degradation. Recent studies confirmed the role of Ndfip1 as a regulator of iron metabolism and pointed out that Ndfip1 was involved in iron homeostasis by regulating the degradation of iron importer divalent metal transporter 1 (DMT1). However, little is known about how Ndfip1 is regulated. The aim of this article was to investigate the regulation of Ndfip1 levels and the possible mechanisms. In this study, we investigated the effect of various stimuli, including iron status and lipopolysaccharide (LPS) on Ndfip1 expression in MES23.5 dopaminergic cell lines. Results showed that Ndfip1 expression in these cells was enhanced by ferrous iron overload, but not ferric iron overload, and decreased after iron deprivation by deferoxamine. In addition, LPS could significantly increase the expression of Ndfip1. Furthermore, we demonstrated that the regulation of Ndfip1 expression by these various stimuli was achieving by activation of nuclear factor-kappa B. We speculate that iron status and LPS may contribute to the changes of Ndfip1 expression by activation of nuclear factor-kappa B.