Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/5832
Title: L-DOPA neurotoxicity is mediated by up-regulation of DMT1 - IRE expression
Authors: Du, F
Qian, ZM
Zhu, L
Wu, XM
Yung, WH
Tsim, TY
Ke, Y
Keywords: Divalent metal transporter-1
Cultured rat astrocytes
Parkinsons-disease
Induced dyskinesia
Transferrin-free
Reactive oxygen
Plasma-membrane
Iron uptake
Brain
Neurons
Issue Date: 25-Feb-2009
Publisher: Public Library of Science
Source: PLoS one, 25 Feb., 2009, v. 4, no. 2, e4593, p. 1-12 How to cite?
Journal: PLoS one 
Abstract: Background: The mechanisms underlying neurotoxicity caused by L-DOPA are not yet completely known. Based on recent findings, we speculated that the increased expression of divalent metal transporter 1 without iron-response element (DMT1-IRE) induced by L-DOPA might play a critical role in the development of L-DOPA neurotoxicity. To test this hypothesis, we investigated the effects of astrocyte-conditioned medium (ACM) and siRNA DMT-IRE on L-DOPA neurotoxicity in cortical neurons.
Methods and Findings: We demonstrated that neurons treated with L-DOPA have a significant dose-dependent decrease in neuronal viability (MTT Assay) and increase in iron content (using a graphite furnace atomic absorption spectrophotometer), DMT1-IRE expression (Western blot analysis) and ferrous iron (55Fe(II)) uptake. Neurons incubated in ACM with or without L-DOPA had no significant differences in their morphology, Hoechst-33342 staining or viability. Also, ACM significantly inhibited the effects of L-DOPA on neuronal iron content as well as DMT1-IRE expression. In addition, we demonstrated that infection of neurons with siRNA DMT-IRE led to a significant decrease in DMT1-IRE expression as well as L-DOPA neurotoxicity.
Conclusion:The up-regulation of DMT1-IRE and the increase in DMT1-IRE-mediated iron influx play a key role in L-DOPA neurotoxicity in cortical neurons.
URI: http://hdl.handle.net/10397/5832
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0004593
Rights: © 2009 Du et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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