Fink D W, Guroff G
Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md 20892.
J Neurochem. 1990 Nov;55(5):1716-26. doi: 10.1111/j.1471-4159.1990.tb04961.x.
The effect of nerve growth factor on the metabolism of arachidonic acid and the hydrolysis of phosphatidylinositol in PC12 cells was examined. Addition of nerve growth factor to PC12 cells isotopically labeled with [3H]arachidonic acid caused an increased release of radioactivity. In a similar manner, treatment of PC12 cells prelabeled with [3H]inositol increased inositol monophosphate accumulation in the presence of LiCl. Stimulation of [3H]arachidonic acid release by nerve growth factor was concentration dependent, attaining a maximum at 0.5 nM. Concentrations of nerve growth factor above 0.5 nM caused less than maximal stimulation. In contrast, nerve growth factor-stimulated accumulation of [3H]inositol monophosphate exhibited a sigmoidal dose-response curve with an apparent maximum at 8 nM. Increased accumulation of [3H]inositol monophosphate could be detected as early as 60 s after nerve growth factor addition, whereas nerve growth factor-stimulated release of [3H]arachidonic acid was not observed until 5 min after nerve growth factor treatment. The nerve growth factor-stimulated release of [3H]arachidonic acid was independent of extracellular calcium concentration. Increased [3H]inositol monophosphate accumulation elicited by nerve growth factor was dependent on the presence of extracellular calcium. These results suggest that the increased metabolism of arachidonic acid and the enhanced hydrolysis of phosphatidylinositol are separately regulated by nerve growth factor.
研究了神经生长因子对PC12细胞中花生四烯酸代谢和磷脂酰肌醇水解的影响。向用[3H]花生四烯酸进行同位素标记的PC12细胞中添加神经生长因子，导致放射性释放增加。同样，用[3H]肌醇预标记的PC12细胞在LiCl存在下处理后，肌醇单磷酸积累增加。神经生长因子对[3H]花生四烯酸释放的刺激呈浓度依赖性，在0.5 nM时达到最大值。高于0.5 nM的神经生长因子浓度引起的刺激小于最大值。相比之下，神经生长因子刺激的[3H]肌醇单磷酸积累呈现出S形剂量反应曲线，在8 nM时出现明显最大值。早在添加神经生长因子后60秒就能检测到[3H]肌醇单磷酸积累增加，而直到神经生长因子处理后5分钟才观察到神经生长因子刺激的[3H]花生四烯酸释放。神经生长因子刺激的[3H]花生四烯酸释放与细胞外钙浓度无关。神经生长因子引起的[3H]肌醇单磷酸积累增加依赖于细胞外钙的存在。这些结果表明，花生四烯酸代谢增加和磷脂酰肌醇水解增强是由神经生长因子分别调节的。
