Espinosa de los Monteros A, Kumar S, Zhao P, Huang C J, Nazarian R, Pan T, Scully S, Chang R, de Vellis J
Mental Retardation Research Center, Department of Neurobiology, Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90024-1759, USA.
Neurochem Res. 1999 Feb;24(2):235-48. doi: 10.1007/s11064-004-1826-2.
It has been established that oligodendrocytes, the myelin forming cells, participate in iron homeostasis through the synthesis and secretion of transferrin. Here we investigated whether a correlation exists between myelination, the commonly studied function of oligodendrocytes, and that of transferrin synthesis and secretion. We used a proteolipid protein mutant, the myelin deficient rat, whose condition is characterized by severe hypomyelination. We compared the ontogenic profile for transferrin gene expression in mutants with that of unaffected rat pups through northern blot analysis and in situ hybridization. Surprisingly, transferrin synthesis was null in mutant oligodendrocytes. Next, we demonstrated that a single apo-transferrin intraparenchymal injection administered to P5 rat pups enabled mutant oligodendrocytes to synthesize myelin basic protein and to myelinate axons, indicating that transferrin effects mutant oligodendrocyte maturation regardless of its source. Thus, transferrin availability is essential for oligodendrocyte maturation and function, and oligodendrocytes are most vulnerable to transferrin deficiency during the premyelinating stage.
已经确定，少突胶质细胞，即形成髓鞘的细胞，通过转铁蛋白的合成和分泌参与铁稳态。在这里，我们研究了髓鞘形成（少突胶质细胞通常被研究的功能）与转铁蛋白合成和分泌功能之间是否存在相关性。我们使用了一种蛋白脂蛋白突变体，即髓鞘缺陷大鼠，其特征是严重髓鞘形成不足。我们通过Northern印迹分析和原位杂交，比较了突变体与未受影响的幼鼠中转铁蛋白基因表达的个体发生谱。令人惊讶的是，突变的少突胶质细胞中转铁蛋白合成缺失。接下来，我们证明，向出生后5天的大鼠幼崽脑实质内注射单次脱铁转铁蛋白，能使突变的少突胶质细胞合成髓鞘碱性蛋白并使轴突形成髓鞘，这表明转铁蛋白无论来源如何都能影响突变少突胶质细胞的成熟。因此，转铁蛋白的可获得性对少突胶质细胞的成熟和功能至关重要，并且少突胶质细胞在髓鞘形成前阶段最易受到转铁蛋白缺乏的影响。
