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.