"MOLECULAR MODE OF ACTION OF NEUROTROPHIC FACTOR,PROSAPOSIN"

丙皂素是激活鞘磷脂水解酶的皂苷的前体，已被确定为神经营养因子。丙皂苷对人神经母细胞瘤细胞、海马神经元和PC 12细胞的神经营养活性存在于丙皂甙C区的NH_2末端亲水性序列。最近的研究表明，睾丸来源的支持细胞脑内移植可以促进6-羟基多巴胺诱导的偏侧帕金森大鼠的功能恢复，体外实验表明，胚胎神经元在生长支持细胞的培养液中培养，可以促进多巴胺能神经元的存活和生长。由于丙皂苷是Sertoli细胞的主要分泌蛋白之一，其对多巴胺能神经元的营养作用是可以想象的。在这里，我们显示了位于大鼠丙皂甙C区NH_2末端亲水性序列中的一个含有18个氨基酸序列的肽(18-肽；LSELIINATEELLIKGL)促进了胚胎第15天大鼠中脑腹侧培养中酪氨酸羟基酶阳性神经元的存活和突起生长。

Prosaposin, the precursor of saposins which activate sphingolipid hydrolases, has been identified as a neurotrophic factor. The neurotrophic activity of prosaposin on human neuroblastoma cells, hippocampal neurons, and PC 12 cells has been shown to reside in the NH_2-terminal hydrophilic sequence of the C-domain of prosaposin. It has recently demonstrated that intracerebral transplantation of testis-derived sertoli cells promotes functional recovery in rats with 6-hydroxydopamine-induced hemiparkinsonism, and in vitro experiments demonstrated enhanced dopaminergic neuronal survival and outgrowth when embryonic neurons were cultured with medium in which rat Sertoli cells had been grown. Since prosaposin is one of the major Sertoli cell secretory proteins, its trophic effect on dopaminergic neurons is conceivable. Here we show that a peptide comprising the 18-amino-acid sequence (18-mer peptide ; LSELIINNATEELLIKGL) located in the NH_2-terminal hydrophilic sequence of the C-domain of rat prosaposin promoted survival and neurite outgrowth of tyrosine hydroxylase-positive neurons on embryonic day 15 rat ventral mesencephalic cultures.