Up-regulated divalent metal transporter 1 by 1-Methyl-4-phenyl-pyridinium iodide (MPP+) enhances iro

• 作 者: ShuzhenZHANG;JunWANG;NingSONG;HongJIANG;Jun-XiaXIE;
• 机 构: Department of Physiology, Medical College of Qingdao University, Qingdao, 266071
• 出 处: 中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the
• 发表日期: 2007年期

　　Based on the previous study,we assume that newly discovered iron transporter,divalent metal transporter 1 (DMT1),might be involved in the MPTP-induced nigral iron accumulation.In the present study,we observed the DMT1 expression and ferrous iron uptake in MPP+ treated MES23.5 dopaminergic cells.The results showed that MPP+ incubation (5 μmol/L) caused an increased expression of both DMT1+IRE and DMT1-IRE in protein level,followed by a significant increase in ferrous iron influx.However,only DMT1-IRE but not DMT1+IRE mRNA expression were up-regulated after MPP+ treatment.Further studies showed that these MPP+-treated cells when loaded with a relative low concentration of ferrous iron showed decreased mitochondrial membrane potential,increased reactive oxygen species (ROS) generation and caspase-3 activation.Our data suggest that increased DMT1 accounts for the increased ferrous iron influx in MPP+ treated MES23.5 cells,and the increased intracellular iron resulted in aggravated apoptosis through the generation of ROS and activation of caspase-3.