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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 |
Issue Date: | 25-Feb-2009 | Source: | PLoS one, 25 Feb., 2009, v. 4, no. 2, e4593, p. 1-12 | 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. |
Keywords: | Divalent metal transporter-1 Cultured rat astrocytes Parkinsons-disease Induced dyskinesia Transferrin-free Reactive oxygen Plasma-membrane Iron uptake Brain Neurons |
Publisher: | Public Library of Science | Journal: | PLoS one | 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. |
Appears in Collections: | Journal/Magazine Article |
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Du_L-DOPA_Neurotoxicity_DMT1.pdf | 4.67 MB | Adobe PDF | View/Open |
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