Qian Z M, Pu Y M, Tang P L, Wang Q
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon.
Neurosci Lett. 1998 Jul 17;251(1):9-12. doi: 10.1016/s0304-3940(98)00486-8.
Excessive brain iron has been found in several neurodegenerative diseases. However, little information is available about mechanism of iron uptake by different types of brain cells including neurons. In this study, transferrin-bound iron (Tf-Fe) accumulation in the cultured cerebellar granule cell was investigated in vitro. After 5 days of culture, the cells were incubated with 1 microM of double-labelled transferrin (1251-Tf-59Fe) at 37 degrees C for 60 min. The cellular Tf-Fe and transferrin (Tf) uptake was analysed. The result showed (1) Tf uptake by the cells increased rapidly at the first 5 min, reaching its maximum after about 20 min of incubation; (2) Tf-Fe uptake kept increasing in a linear manner during the whole period of incubation; (3) the addition of either NH4Cl or CH3NH2, the blockers of Tf-Fe uptake via inhibiting iron release from Tf within endosomes, decreased the cellular Tf-Fe uptake but had no significant effect on Tf uptake; (4) trypsin and unlabelled Tf-Fe inhibited the uptake rate of Tf-Fe as well as Tf. The results suggested that Tf-Fe transport across the membrane of this type of neuron, much like other mammalian cells, was mediated by Tf-TfR endocytosis. Dysfunction of Tf or TfR would possibly lead to iron irregulation in the brain and consequently cause damage to neuronal functions.
在几种神经退行性疾病中已发现脑铁过量。然而，关于包括神经元在内的不同类型脑细胞摄取铁的机制，目前所知甚少。在本研究中，体外研究了培养的小脑颗粒细胞中转铁蛋白结合铁（Tf-Fe）的积累情况。培养5天后，将细胞在37℃下与1μM双标记转铁蛋白（125I-Tf-59Fe）孵育60分钟。分析细胞对Tf-Fe和转铁蛋白（Tf）的摄取情况。结果显示：（1）细胞对Tf的摄取在最初5分钟迅速增加，孵育约20分钟后达到最大值；（2）在整个孵育期间，Tf-Fe的摄取以线性方式持续增加；（3）加入NH4Cl或CH3NH2，这两种通过抑制内体中Tf释放铁来阻断Tf-Fe摄取的物质，可降低细胞对Tf-Fe的摄取，但对Tf摄取无显著影响；（4）胰蛋白酶和未标记的Tf-Fe抑制Tf-Fe以及Tf的摄取速率。结果表明，这种类型的神经元细胞膜上Tf-Fe的转运，与其他哺乳动物细胞非常相似，是由Tf-TfR内吞作用介导的。Tf或TfR功能障碍可能会导致脑内铁调节异常，进而损害神经元功能。
