Neurotrophic factor production in human astrocytoma cells by 2,5,6-tribromogramine via activation of epsilon isoform of protein kinase C.
Neurotrophic factor production in human astrocytoma cells by 2,5,6-tribromogramine via activation of epsilon isoform of protein kinase C.
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DOI：
10.1016/j.ejps.2006.02.004
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发表时间：
2006-07
期刊：
影响因子：
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通讯作者：
Masaki Saito;Megumi Hori;Y. Obara;Y. Ohizumi;S. Ohkubo;N. Nakahata
中科院分区：
文献类型：
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作者：
Masaki Saito;Megumi Hori;Y. Obara;Y. Ohizumi;S. Ohkubo;N. Nakahata
已知星形胶质细胞分泌多种神经营养因子以促进神经元的存活。对于神经元疾病的治疗，诱导神经营养因子合成的低分子量化合物是有用的，因为神经营养因子是不能穿过血脑屏障的多肽。当大鼠嗜铬细胞瘤（PC-12）细胞在用2，5，6-三溴芦竹碱处理的人星形细胞瘤细胞（1321 N1）的培养基中培养时，它们分化为具有神经突的神经元样细胞，表明2，5，6-三溴芦竹碱从1321 N1细胞释放神经营养因子。事实上，2，5，6-三溴芦竹碱通过mRNA表达增加神经生长因子（NGF）蛋白的合成和分泌。2，5，6-三溴芦竹碱和佛波醇12，13-肉豆蔻酸酯一样抑制卡巴胆碱诱导的肌醇磷酸水解。双吲哚马来酰亚胺I（GF 109203 X），一种特异性的蛋白激酶C（PKC）抑制剂，恢复抑制作用，表明2，5，6-三溴芦竹碱可能激活PKC。GF 109203 X还能抑制2，5，6-三溴芦竹碱诱导的PC-12细胞形态分化。2，5，6-三溴芦竹碱可使PKC-β从胞浆部分转移到膜部分，但不使PKC-α或PKC-β转移到膜部分。这些结果表明，2，5，6-三溴芦竹碱通过激活PKC β促进1321 N1细胞合成和分泌包括NGF在内的神经营养因子。
It is known that astrocytes secrete several neurotrophic factors to promote the survival of neurons. For the treatment of neuronal disorders, low molecular weight compounds inducing neurotrophic factor synthesis are useful, because neurotrophic factors are polypeptides which cannot cross the blood brain barrier. When rat pheochromocytoma (PC-12) cells were cultivated in the medium of human astrocytoma cells (1321N1) treated with 2,5,6-tribromogramine, they differentiated to neuron-like cells possessing neurites, indicating that 2,5,6-tribromogramine released neurotrophic factors from 1321N1 cells. In fact, 2,5,6-tribromogramine increased nerve growth factor (NGF) protein synthesis and secretion through mRNA expression. 2,5,6-Tribromogramine inhibited carbachol-induced phosphoinositide hydrolysis as well as phorbol 12,13-myristate acetate did. The inhibition was recovered by bisindolylmaleimide I (GF109203X), a specific protein kinase C (PKC) inhibitor, indicating that 2,5,6-tribromogramine may activate PKC. The morphological differentiation of PC-12 cells by the medium treated with 2,5,6-tribromogramine was also reduced by GF109203X. 2,5,6-Tribromogramine translocated PKC-ɛ but not PKC-α or PKC-ζ, to membrane fraction from cytosol fraction. These results indicate that 2,5,6-tribromogramine promotes the synthesis and secretion of neurotrophic factors including NGF in 1321N1 cells via an activation of PKC-ɛ.