Increased DMT1 expression and iron content in MPTP-treated C57BL/6 mice

Abstract

铁在帕金森病(Parkinson’s disease,PD)的发病机制中起着非常关键的作用,为了探讨PD中铁升高的机制,本实验观察了1-甲基-4-苯基-1,2,3,6--四氢吡啶(MPTP)处理小鼠黑质(substantia nigra,SN)内铁摄取及新的铁转运蛋白二价金属离子转运蛋白1(DMT1)的表达变化。结果表明:(1)MPTP处理组小鼠SN内铁染色增高,注射MPTP 7d组明显高于3 d组。(2)MPTP处理组小鼠,酪氨酸羟化酶(TH)免疫阳性细胞数目显著减少。(3)MPTP处理组小鼠,“-IRE”型 DMT1表达在各组中均增加,而“+IRE”型DMT1仅在MPTP处理后7 d才出现变化。上述结果提示,这种新发现的哺乳动物跨膜铁转运蛋白表达增加可能是引起MPTP处理小鼠SN中铁升高的关键因素,铁的升高进一步导致DA神经元的死亡。 Iron plays a key role in Parkinson’s disease (PD). To illustrate the mechanism underlyingthe increase of iron in substantia nigra (SN) in PD, changes of the expression of divalent metal transporter1 (DMT1 ) and iron content were examined in SN in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) treated mice using immunohistochemistry and histochemistry respectively. Following MPTP treat-ment for 3 d, elevated iron staining was found in SN. A further increase in iron content was observed after7 d. In these lesioned animals, tyrosine hydroxylase -immunoreactive DA neurons exhibited a decrease innumber and morphological changes as well. There were two isoforms of DMT1 expressed in SN of mice. Af-ter MPTP treatment, the expression of DMT1 without IRE form increased in either group, whereas DMT1with IRE form increased only after 7 d of MPTP treatment. These observations suggest that DMT1 is possiblyinvolved in the process of iron accumulation in SN of MPTP-treated mice, which might be responsible forthe subsequent death of DA neurons.