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Ndfip1 attenuated 6-OHDA-induced iron accumulation via regulating the degradation of DMT1.
Neurobiol Aging. 2015 Feb; 36(2):1183-93.NA

Abstract

Elevated iron levels and increased expression of divalent metal transporter 1 (DMT1) in the substantia nigra of Parkinson's disease (PD) have been reported. Nedd4 family-interacting protein 1 (Ndfip1), an adaptor protein for the Nedd4 family of ubiquitin ligases, played an essential role in regulating DMT1 and iron homeostasis in human cortical neurons. In this study, we demonstrated that the expression of Ndfip1 decreased in 6-hydroxydopamine (6-OHDA)-induced PD rats and 6-OHDA-treated MES23.5 dopaminergic cells. Further study showed that the decrease of Ndfip1 occurred earlier than the increase of DMT1 with iron-responsive element (DMT1 + IRE) in 6-OHDA-treated MES23.5 cells, indicating that the decrease of Ndfip1 might be involved in the increase of DMT1 + IRE. In addition, we demonstrated that overexpression of Ndfip1 caused DMT1 + IRE downregulation, resulting in the decreased iron influx and iron-induced neurotoxicity. Although Ndfip1 knockdown led to decreased protein levels of DMT1 + IRE, partially aggravated iron-induced neurotoxicity. Further experiments showed that 6-OHDA-induced decrease in Ndfip1 levels might be related to proteasomal and lysosomal activations and oxidative stress caused by 6-OHDA. These data suggest that decreased Ndfip1 expression might contribute to the pathogenesis of 6-OHDA-induced iron accumulation and Ndfip1 could attenuate 6-OHDA-induced iron accumulation via regulating the degradation of DMT1.

Authors+Show Affiliations

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China.Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China.Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China.Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China.Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China. Electronic address: jxiaxie@public.qd.sd.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25467637

Citation

Jia, Wenting, et al. "Ndfip1 Attenuated 6-OHDA-induced Iron Accumulation Via Regulating the Degradation of DMT1." Neurobiology of Aging, vol. 36, no. 2, 2015, pp. 1183-93.
Jia W, Xu H, Du X, et al. Ndfip1 attenuated 6-OHDA-induced iron accumulation via regulating the degradation of DMT1. Neurobiol Aging. 2015;36(2):1183-93.
Jia, W., Xu, H., Du, X., Jiang, H., & Xie, J. (2015). Ndfip1 attenuated 6-OHDA-induced iron accumulation via regulating the degradation of DMT1. Neurobiology of Aging, 36(2), 1183-93. https://doi.org/10.1016/j.neurobiolaging.2014.10.021
Jia W, et al. Ndfip1 Attenuated 6-OHDA-induced Iron Accumulation Via Regulating the Degradation of DMT1. Neurobiol Aging. 2015;36(2):1183-93. PubMed PMID: 25467637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ndfip1 attenuated 6-OHDA-induced iron accumulation via regulating the degradation of DMT1. AU - Jia,Wenting, AU - Xu,Huamin, AU - Du,Xixun, AU - Jiang,Hong, AU - Xie,Junxia, Y1 - 2014/10/18/ PY - 2014/03/16/received PY - 2014/09/28/revised PY - 2014/10/14/accepted PY - 2014/12/4/entrez PY - 2014/12/4/pubmed PY - 2015/9/22/medline KW - 6-OHDA KW - Divalent metal transporter 1 KW - Iron KW - Ndfip1 KW - Parkinson's disease SP - 1183 EP - 93 JF - Neurobiology of aging JO - Neurobiol Aging VL - 36 IS - 2 N2 - Elevated iron levels and increased expression of divalent metal transporter 1 (DMT1) in the substantia nigra of Parkinson's disease (PD) have been reported. Nedd4 family-interacting protein 1 (Ndfip1), an adaptor protein for the Nedd4 family of ubiquitin ligases, played an essential role in regulating DMT1 and iron homeostasis in human cortical neurons. In this study, we demonstrated that the expression of Ndfip1 decreased in 6-hydroxydopamine (6-OHDA)-induced PD rats and 6-OHDA-treated MES23.5 dopaminergic cells. Further study showed that the decrease of Ndfip1 occurred earlier than the increase of DMT1 with iron-responsive element (DMT1 + IRE) in 6-OHDA-treated MES23.5 cells, indicating that the decrease of Ndfip1 might be involved in the increase of DMT1 + IRE. In addition, we demonstrated that overexpression of Ndfip1 caused DMT1 + IRE downregulation, resulting in the decreased iron influx and iron-induced neurotoxicity. Although Ndfip1 knockdown led to decreased protein levels of DMT1 + IRE, partially aggravated iron-induced neurotoxicity. Further experiments showed that 6-OHDA-induced decrease in Ndfip1 levels might be related to proteasomal and lysosomal activations and oxidative stress caused by 6-OHDA. These data suggest that decreased Ndfip1 expression might contribute to the pathogenesis of 6-OHDA-induced iron accumulation and Ndfip1 could attenuate 6-OHDA-induced iron accumulation via regulating the degradation of DMT1. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/25467637/Ndfip1_attenuated_6_OHDA_induced_iron_accumulation_via_regulating_the_degradation_of_DMT1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(14)00679-4 DB - PRIME DP - Unbound Medicine ER -