HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Increased divalent metal transporter 1 expression might be associated with the neurotoxicity of L-DOPA.

Abstract
Based on the available data, we speculated that changes in brain iron metabolism induced by L-DOPA might be associated with the neurotoxicity of L-DOPA. To investigate this possibility, the effects of L-DOPA on the expression of iron influx proteins [transferrin receptor (TfR) and divalent metal transporter 1 (DMT1)], iron efflux protein (ferroportin 1), and iron uptake in C6 glioma cells were determined in this study using Northern blot and Western blot analysis and the calcein method. The findings showed that treatment of C6 cells with different concentrations of L-DOPA (0-100 microM) did not affect the expression of mRNA and protein of TfR and DMT1 with iron-responsive element (+IRE) and protein of ferroportin 1. However, a significant increase in the expression of DMT1(-IRE) mRNA and protein was found in cells treated, respectively, with 10 and 30 microM L-DOPA (mRNA) and 1, 5, 10 and 30 microM L-DOPA (protein). The increase in DMT(-IRE) protein induced by L-DOPA treatment was in parallel with the increase in DMT(-IRE) mRNA. The levels of DMT1(-IRE) mRNA and protein peaked in the cells treated with 10 microM L-DOPA and then decreased progressively with increasing concentrations of L-DOPA. Further study demonstrated that treatment of the cells with 10 microM L-DOPA induced a significant increase in ferrous uptake by C6 glioma cells. The findings suggested that the increased DMT1(-IRE) expression might be partly associated with the neurotoxicity of L-DOPA. Clinical relevance of the findings needs to be investigated further.
AuthorsYan-Zhong Chang, Ya Ke, Jun-Rong Du, Georges M Halpern, Kwok-Ping Ho, Li Zhu, Xiao-Song Gu, You-Jia Xu, Qin Wang, Lian-Zhi Li, Chen-Yuen Wang, Zhong-Ming Qian
JournalMolecular pharmacology (Mol Pharmacol) Vol. 69 Issue 3 Pg. 968-74 (Mar 2006) ISSN: 0026-895X [Print] United States
PMID16317110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cation Transport Proteins
  • Chelating Agents
  • Phenanthrolines
  • RNA, Messenger
  • Receptors, Transferrin
  • metal transporting protein 1
  • bathophenanthroline disulfonic acid
  • Levodopa
  • Iron
Topics
  • Animals
  • Brain (drug effects, metabolism)
  • Cation Transport Proteins (genetics, metabolism)
  • Chelating Agents (pharmacology)
  • Ion Transport (drug effects)
  • Iron (metabolism)
  • Levodopa (toxicity)
  • Phenanthrolines (pharmacology)
  • RNA, Messenger (analysis, metabolism)
  • Rats
  • Receptors, Transferrin (genetics, metabolism)
  • Tumor Cells, Cultured
  • Up-Regulation

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: