Neuronal Differentiation of Neural Progenitor Cells by Intracellular Delivery of Synthetic Oligopeptide Derived from Von Hippel-Lindau Protein
Neuronal Differentiation of Neural Progenitor Cells by Intracellular Delivery of Synthetic Oligopeptide Derived from Von Hippel-Lindau Protein
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DOI：
10.2174/092986609789353691
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发表时间：
2009-01-01
影响因子：
1.6
通讯作者：
Sugimoto, Naoki
中科院分区：
文献类型：
--
作者：
Kanno, Hiroshi;Nakano, Shuichi;Sugimoto, Naoki
合成寡肽的细胞内递送具有促进各种细胞事件如细胞死亡、增殖、生长抑制、代谢变化和形态学变化的发生的潜力。然而，通过细胞内递送合成寡肽来调节细胞分化的研究很少。Von Hippel-Lindau蛋白（pVHL）是一种具有诱导神经前体细胞分化功能的蛋白质。为了在这些细胞中发挥作用，pVHL形成由自身、延伸蛋白BC、Clu-2和Rbx-1组成的复合物。这表明pVHL中延伸蛋白BC的结合位点在pVHL功能中起关键作用，即，泛素化，这与神经元分化有关。因此，我们合成了对应于延伸蛋白BC结合位点的寡肽，并通过使用三氟乙酰化脂多胺和二碘酰磷脂酰乙醇胺（BioPorter）的混合物将寡肽递送到NPC中以形成肽-脂质复合物。在细胞内递送寡肽后，在神经突生长方面以及通过免疫细胞化学和电生理手段显示NPC的分化诱导。将pVHL合成的寡肽导入细胞内，为NPCs的神经元分化提供了一种安全、有价值的途径。
Intracellular delivery of synthetic oligopeptides has the potential to promote the occurrence of various cellular events such as cell death, proliferation, growth inhibition, metabolic changes, and morphological changes. However, the regulation of cellular differentiation by intracellular delivery of synthetic oligopeptides has been little studied. Von Hippel-Lindau protein (pVHL) is one of the proteins that functions to induce the differentiation of neural progenitor cells (NPCs). To function in these cells, pVHL forms a complex composed of itself, elongin BC, Clu-2, and Rbx-1. It is suggested that the binding site of elongin BC in pVHL plays a critical role in pVHL function, i.e., ubiquitination, which is related to neuronal differentiation. So, we synthesized an oligopeptide corresponding to the elongin BC binding site, and delivered the oligopeptide into NPCs by using a mixture of trifluoroacetylated lipopolyamine and diloeoyl phosphatidylethanolamine (BioPorter) to form a peptide-lipid complex. After intracellular delivery of the oligopeptide, induction of differentiation of NPCs was shown in terms of neurite outgrowth and by immunocytochemical and electrophysiological means. The intracellular delivery of the synthetic oligopeptide derived from pVHL may provide a safe and valuable approach for the neuronal differentiation of NPCs.