Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor.
Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor.
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发表时间：
1992-10
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通讯作者：
K. Asai;K. Nakanishi;I. Isobe;Y. Eksioglu;A. Hirano;K. Hama;T. Miyamoto;T. Kato
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作者：
K. Asai;K. Nakanishi;I. Isobe;Y. Eksioglu;A. Hirano;K. Hama;T. Miyamoto;T. Kato
Gliostatin是表观M（r）= 100，000的多肽生长抑制剂，具有包含两个50-kDa亚基的同源二聚体结构，作用于星形胶质细胞以及星形细胞瘤细胞（Asai，K.，Hirano，T.，Kaneko，S.，Moriyama，A.，Nakanishi，K.，矶部岛Eksioglu，Y.Z.，和Kato，T.（1992）神经化学杂志，59，307-317）。包括氨基末端的13种胰蛋白酶肽的氨基酸序列与血小板衍生的内皮细胞生长因子（PD-ECGF）的氨基酸序列完全相同（石川，F.，Miyazono，K.，赫尔曼，美国，德雷克斯勒，H.，Wernstedt，C.，Hagiwara，K.，Kagalki，K.，Takaku，F.，Risau，W.，Heldin，C.- H.（1989）Nature 338，557-562）。Gliostatin和人胎盘PD-ECGF对胶质细胞有生长抑制作用，对内皮细胞有生长促进作用，且对胶质细胞生长的半数抑制量相近（ID 50 = 1.3 nM）和内皮生长促进的半数最大浓度（EC 50 = 1.0 nM），表明这两种因子通过每个细胞表面上的相同受体引起生物学作用。我们已经进一步证明了一种新的神经营养作用的gliostatin/PD-ECGF对胚胎大鼠皮层神经元的文化的证据。神经营养作用的半最大浓度的gliostatin/PD-ECGF是0.3 nM。对神经胶质细胞、内皮细胞和神经元细胞的所有作用均被抗胶质细胞生长抑制素的单克隆抗体所消除。这些数据表明，gliostatin/PD-ECGF可能在中枢神经系统的发育和再生中发挥重要作用，还可能参与诱导血管生成以形成血脑屏障。
Gliostatin is a polypeptide growth inhibitor of apparent M(r) = 100,000 with a homodimeric structure comprising two 50-kDa subunits, acting on astrocyte as well as astrocytoma cells (Asai, K., Hirano, T., Kaneko, S., Moriyama, A., Nakanishi, K., Isobe, I., Eksioglu, Y.Z., and Kato, T. (1992) J. Neurochem., 59, 307-317). The amino acid sequences of 13 tryptic peptides including the amino terminus were completely identical to those of platelet-derived endothelial cell growth factor (PD-ECGF) (Ishikawa, F., Miyazono, K., Hellman, U., Drexler, H., Wernstedt, C., Hagiwara, K., Usuki, K., Takaku, F., Risau, W., and Heldin, C.-H. (1989) Nature 338, 557-562). Gliostatin and PD-ECGF, purified from human placenta, shared growth inhibition on glial cells and growth promotion on endothelial cells, and exhibited similar values for half-maximal dose of glial growth inhibition (ID50 = 1.3 nM) and the half-maximal concentration of endothelial growth promotion (EC50 = 1.0 nM), suggesting that both factors evoke the biological actions through an identical receptor on each cell surface. We have further demonstrated evidence of a novel neurotrophic action of gliostatin/PD-ECGF toward embryonic rat cortical neurons in culture. The half-maximal concentration of gliostatin/PD-ECGF for neurotrophic action was 0.3 nM. All actions on glial, endothelial, and neuronal cells, were abolished by a monoclonal antibody against gliostatin. These data indicate that gliostatin/PD-ECGF may play important roles on development and regeneration of the central nervous system and may also involve the induction of angiogenesis for the formation of blood brain barrier.