title: 6-Hydroxydopamine promotes iron traffic in primary cultured astrocytes.
abstract: It is well known that disrupted brain iron homeostasis was involved in Parkinson's disease. We previously reported 6-hydroxydopamine (6-OHDA) could enhance iron influx and attenuate iron efflux process, thus promote iron accumulation in neurons. Astrocytes, the major glial cell type in the central nervous system, are largely responsible for iron distribution in the brain. However, how iron metabolism changes in astrocytes with 6-OHDA treatment are not fully elucidated. In the present study, we first observed that both iron influx and efflux were enhanced with 10 μM 6-OHDA treatment for 24 h in primary cultured astrocytes. In accordance with these iron traffic modulations, both mRNA and protein levels of iron importer divalent metal transporter 1 with iron responsive element (DMT1+IRE) and exporter ferroportin 1 (FPN1) were up-regulated in these cells. L-ferritin mRNA levels were increased. Iron regulatory protein 1 (IRP1) showed a dynamic regulation with 6-OHDA treatment, as indicated by a moderate up-regulation at 12 h, however, down-regulation at 24 h. We further demonstrated that 6-OHDA treatment could induce activation of nuclear factor-kappaB (NF-κB) p65. IκBα activation inhibitor BAY11-7082 fully blocked 6-OHDA induced NF-κB p65 phosphorylation and DMT1 + IRE up-regulation. These results suggest that 6-OHDA might promote iron transport rate in astrocytes by regulating iron transporters, IRP1 expression and NF-κB p65 activation, indicating a different response between neurons and astrocytes.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, China.
authors.forename: Hao-Yun
authors.initials: HY
authors.lastname: Zhang
authors.forename: Nai-Dong
authors.initials: ND
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.forename: Hua-Min
authors.initials: HM
authors.lastname: Xu
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Shi
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Xie
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects*; D002478:Cells, Cultured; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D051996:Transcription Factor RelA; D016627:Oxidopamine; D007501:Iron; D035941:Iron Regulatory Protein 1