High hepcidin level accounts for the nigral iron accumulation in acute peripheral iron intoxication rats.
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.
Department of Neurology, The Affiliated Hospital of Medial College, Qingdao University, Qingdao 266003, China.
Chao
C
Sun
Ning
N
Song
Anmu
A
Xie
Junxia
J
Xie
Hong
H
Jiang
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000633:toxicity*; D001923:Brain Chemistry; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D064451:Hepcidins; D006801:Humans; D058085:Iron Compounds / Q000378:metabolism / Q000633:toxicity*; D019189:Iron Metabolism Disorders; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000098742:Ferroportin
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578702:HAMP protein, human; C578703:Hamp protein, rat; D064451:Hepcidins; D058085:Iron Compounds; D012333:RNA, Messenger; D000098742:Ferroportin