Golub M S, Han B, Keen C L
Department of Internal Medicine, University of California, Davis, 95616, USA.
Neurotoxicology. 1999 Dec;20(6):961-70.
Transferrin (Tf) is known primarily for its role in the transport and cellular uptake of iron (Fe). Tf is also the major serum binding protein for Al. In this study, primary rat oligodendrocyte, neuron and astrocyte cultures were found to differ in Tf mediated Fe and Al uptake and in the effect of Al-Tf on Fe-Tf uptake during 4 h incubation periods. When incubated with Al-Tf (1.25 microM), oligodendrocytes displayed a 3- to 4-fold increase (p=.0002) in Al, neurons demonstrated a much smaller (p=.06) increase, and no increase was seen for astrocytes. When incubated with equimolar Al citrate or Al chloride, no increase in cellular Al was seen in any of the three cell types. Oligodendrocytes, astrocytes and neurons all demonstrated greater 59Fe uptake from Fe-Tf than Fe chloride. This uptake could be inhibited by excess Fe-Tf in oligodendrocytes and neurons, but not astrocytes. A small but significant inhibition of 59Fe uptake from Fe-Tf was seen after addition of Al-Tf to the incubation medium of oligodendrocytes, but not neurons or astrocytes. Oligodendrocytes may be particularly vulnerable to the accumulation of excess intracellular Al, and to interference of Al with Fe uptake. Such effects could contribute to Al-induced neurotoxicity if they result in altered myelin formation or maintenance.
转铁蛋白（Tf）主要因其在铁（Fe）的运输和细胞摄取中的作用而闻名。Tf也是铝的主要血清结合蛋白。在本研究中，发现原代大鼠少突胶质细胞、神经元和星形胶质细胞培养物在Tf介导的铁和铝摄取以及铝 - Tf对铁 - Tf摄取的影响方面，在4小时孵育期内存在差异。当与铝 - Tf（1.25微摩尔）一起孵育时，少突胶质细胞中的铝含量增加了3至4倍（p = 0.0002），神经元的增加幅度小得多（p = 0.06），而星形胶质细胞则未见增加。当与等摩尔的柠檬酸铝或氯化铝一起孵育时，三种细胞类型中的任何一种细胞内铝含量均未见增加。少突胶质细胞、星形胶质细胞和神经元从铁 - Tf摄取的59Fe均比从氯化铁摄取的多。这种摄取在少突胶质细胞和神经元中可被过量的铁 - Tf抑制，但在星形胶质细胞中则不能。在少突胶质细胞的孵育培养基中添加铝 - Tf后，观察到从铁 - Tf摄取的59Fe有轻微但显著的抑制，而在神经元或星形胶质细胞中则未观察到。少突胶质细胞可能特别容易受到细胞内过量铝积累以及铝对铁摄取的干扰的影响。如果这些影响导致髓鞘形成或维持改变，可能会导致铝诱导的神经毒性。
