Increased divalent metal transporter 1 expression might be associated with the neurotoxicity of L-DOPA.
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.
Chang
Yan-Zhong
YZ
Department of Applied Biology and Chemistry Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
Ke
Ya
Y
Du
Jun-Rong
JR
Halpern
Georges M
GM
Ho
Kwok-Ping
KP
Zhu
Li
L
Gu
Xiao-Song
XS
Xu
You-Jia
YJ
Wang
Qin
Q
Li
Lian-Zhi
LZ
Wang
Chen-Yuen
CY
Qian
Zhong-Ming
ZM
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D007980:Levodopa / Q000633:toxicity*; D010618:Phenanthrolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000098742:Ferroportin
D027682:Cation Transport Proteins; D002614:Chelating Agents; D010618:Phenanthrolines; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D000098742:Ferroportin; C017049:bathophenanthroline disulfonic acid; D007980:Levodopa; D007501:Iron