6-羟基多巴处理后星形胶质细胞铁转运能力的改变.doc

6-羟基多巴处理后星形胶质细胞铁转运能力的改变.doc

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 6-Hydroxydopamine Promotes Iron Traffic in Primary Cultured Astrocytes# ZHANG Haoyun, SONG Ning, XU Huamin, SHI Limin, JIANG Hong, XIE Junxia** 5 10 15 20 25 30 35 40 (Department of Physiology, Medical College of Qingdao University, ShanDong QingDao 266071) Abstract: It is well known that disrupted brain iron homeostasis was involved in Parkinson’s disease (PD). 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 of astrocytes in PD 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 hrs in primary cultured astrocytes. In accordance with this iron traffic modulations, iron importer divalent metal transporter 1 with iron responsive element (DMT1+IRE) and exporter ferroportin 1 (FPN1) were up-regulated in these cells. Iron regulatory protein 1 (IRP1) showed a dynamic regulation with 6-OHDA treatment, as indicated by a moderate up-regulation at 12 hrs, however, down-regulation at 24 hrs. These results suggest that 6-OHDA might promote iron transport rate in astocytes by regulating iron transporters and IRP1 expression. Keywords: Parkinson’s disease; astrocytes; iron; iron transport; oxidative stress 0 Introduction Parkinson’s disease (PD) is a neurodegenerative disorder characterized in its late phase by the sustained loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) [1,2,3]. Two of pathological features in PD are the aggregation of oxidative stress and nigral iron deposit [4,5,6,7]. Excessive iron enhances the production of oxygen radicals and thus is associated with oxidative damage and eventually neuronal degeneration in this region. So far most of the studies are concerned with iron accumulation in melanized dopaminergic neurons. Little is known about the contribution of astrocytes to this iron accumulation under oxidative circu

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