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Iron status and lipopolysaccharide regulate Ndfip1 by activation of nuclear factor-kappa B

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Abstract

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.

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Acknowledgments

This work was supported by grants from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2011CB504102), the National Foundation of Natural Science of China (30930036, 81100955, 31371081, 81171208). Ministry of Education of China (20103706120001), Department of Science & Technology of Shandong Province (BS2010SW009), Shandong Provincial Education Department (J11LC05) and Department of Health of Shandong (2011QZ006).

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Authors and Affiliations

  1. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, China

    Huamin Xu, Wenting Jia, Hong Jiang & Junxia Xie

  2. Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China

    Qing Chang & Peng Sun

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  1. Huamin Xu
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  2. Qing Chang
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  3. Wenting Jia
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  4. Hong Jiang
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  5. Peng Sun
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  6. Junxia Xie
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Correspondence to Peng Sun or Junxia Xie.

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Huamin Xu and Qing Chang are the co-first authors.

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Xu, H., Chang, Q., Jia, W. et al. Iron status and lipopolysaccharide regulate Ndfip1 by activation of nuclear factor-kappa B. Biometals 26, 981–988 (2013). https://doi.org/10.1007/s10534-013-9674-7

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