Quach T T, Duchemin A M, Oliver A P, Schrier B K, Wyatt R J
Molecular Neurobiology Unit, NICHD, NIH, Bethesda, MD 20892.
Brain Res Dev Brain Res. 1992 Jul 24;68(1):97-102. doi: 10.1016/0165-3806(92)90251-q.
The synthetic undecameric peptide, pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe, known as the hydra head activator peptide, present in high concentrations in mammalian hypothalamus and intestine, was tested for neurotrophic activity in a survival assay using cultured chick embryonic sympathetic and dorsal root ganglion cells, and for morphological differentiation activity on neuroblastoma cells. Hydra head activator peptide supported neuron survival. The optimal active concentration, 1 pM, was very similar to the concentration that causes bud and head formation in hydra. Maximal neuron survival obtained with hydra head activator peptide was close to that obtained with nerve growth factor: both substances enhanced survival up to 3 times that of control cultures. Bradykinin, which has some amino acid sequence homology with hydra head activator, was inactive as a neurotrophic factor. Hydra head activator induced rapid morphological differentiation of the mouse neuroblastoma cell line Neuro-2A. Neuro-2A responded to the peptide by process extension, 4 h after its addition to the culture medium. Neurotrophic factors isolated to date have been characterized by their ability to maintain cell viability and enhance neurite outgrowth. Hydra head activator peptide met these two criteria when tested in 3 different neuron culture systems. Our results suggest that the head activator peptide may act as a neurotrophic factor for neurons in other species, including mammals.
合成的十一肽pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe，即九头蛇头部激活肽，在哺乳动物下丘脑和肠道中高浓度存在，在一项使用培养的鸡胚交感神经和背根神经节细胞的存活试验中测试其神经营养活性，并在神经母细胞瘤细胞上测试其形态分化活性。九头蛇头部激活肽支持神经元存活。最佳活性浓度为1 pM，与在九头蛇中引起芽和头部形成的浓度非常相似。用九头蛇头部激活肽获得的最大神经元存活率接近用神经生长因子获得的存活率：两种物质都将存活率提高到对照培养物的3倍。缓激肽与九头蛇头部激活肽有一些氨基酸序列同源性，作为神经营养因子无活性。九头蛇头部激活肽诱导小鼠神经母细胞瘤细胞系Neuro-2A快速形态分化。将肽添加到培养基中4小时后，Neuro-2A通过突起延伸对其作出反应。迄今为止分离出的神经营养因子的特征在于它们维持细胞活力和增强神经突生长的能力。在3种不同的神经元培养系统中进行测试时，九头蛇头部激活肽符合这两个标准。我们的结果表明，头部激活肽可能作为包括哺乳动物在内的其他物种中神经元的神经营养因子发挥作用。
