Hepcidin is considered to be a circulatory
hormone and a major mechanism regulating
iron homeostasis. Our previous publication revealed that acute
iron intoxication induced
iron deposit and dopaminergic neuron degeneration in the substantia nigra (SN) of a rat model. However, whether and how
hepcidin functions in this nigral
iron accumulation has not been elucidated. In the present study, we observed a decreased of FPN1
protein level in the SN triggered by peripheral
iron overload within 4 h, which correlated with a high
hepcidin level. To further investigate the role of intracellular
hepcidin under
iron overload circumstances, we assessed the expression of
hepcidin mRNA and FPN1
protein in vitro. We observed that
hepcidin mRNA level was up-regulated and FPN1
protein level was down-regulated in MES23.5 dopaminergic cells in a period of 4h incubation with
iron. Both in pCMV-XL4-hepcidin transfected and
hepcidin-treated cells, decreased FPN1
protein levels were observed. Our data provide direct evidence that the role for intracellular
hepcidin generated in the SN is particularly relevant to restrict
iron release by down-regulation FPN1 expression in this region, thus an important contributor to the abnormal
iron deposit occurred at an early stage in conditions of peripheral
iron intoxication.