Sugitani Kayo, Koriyama Yoshiki, Ogai Kazuhiro, Wakasugi Keisuke, Kato Satoru
Department of Clinical Laboratory Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, 920-0942, Kanazawa, Japan.
Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Sciences, 3500-3 Minamitamagaki, 513-8670, Suzuka, Mie, Japan.
Adv Exp Med Biol. 2016;854:671-5. doi: 10.1007/978-3-319-17121-0_89.
Neuroglobin (Ngb) is a new member of the family of heme proteins and is specifically expressed in neurons of the central and peripheral nervous systems in all vertebrates. In particular, the retina has a 100-fold higher concentration of Ngb than do other nervous tissues. The role of Ngb in the retina is yet to be clarified. Therefore, to understand the functional role of Ngb in the retina after optic nerve injury (ONI), we used two types of retina, from zebrafish and mice, which have permissible and non-permissible capacity for nerve regeneration after ONI, respectively. After ONI, the Ngb protein in zebrafish was upregulated in the amacrine cells within 3 days, whereas in the mouse retina, Ngb was downregulated in the retinal ganglion cells (RGCs) within 3 days. Zebrafish Ngb (z-Ngb) significantly enhanced neurite outgrowth in retinal explant culture. According to these results, we designed an overexpression experiment with the mouse Ngb (m-Ngb) gene in RGC-5 cells (retinal precursor cells). The excess of m-Ngb actually rescued RGC-5 cells under hypoxic conditions and significantly enhanced neurite outgrowth in cell culture. These data suggest that mammalian Ngb has positive neuroprotective and neuritogenic effects that induce nerve regeneration after ONI.
神经球蛋白（Ngb）是血红素蛋白家族的新成员，在所有脊椎动物的中枢和外周神经系统的神经元中特异性表达。特别是，视网膜中Ngb的浓度比其他神经组织高100倍。Ngb在视网膜中的作用尚待阐明。因此，为了了解视神经损伤（ONI）后Ngb在视网膜中的功能作用，我们使用了两种视网膜，分别来自斑马鱼和小鼠，它们在ONI后分别具有允许和不允许神经再生的能力。ONI后，斑马鱼中的Ngb蛋白在3天内在无长突细胞中上调，而在小鼠视网膜中，Ngb在3天内在视网膜神经节细胞（RGCs）中下调。斑马鱼Ngb（z-Ngb）在视网膜外植体培养中显著增强了神经突生长。根据这些结果，我们设计了在RGC-5细胞（视网膜前体细胞）中过表达小鼠Ngb（m-Ngb）基因的实验。过量的m-Ngb实际上在缺氧条件下挽救了RGC-5细胞，并在细胞培养中显著增强了神经突生长。这些数据表明，哺乳动物Ngb具有积极的神经保护和促神经突生长作用，可在ONI后诱导神经再生。
