Kalberg C, Yung S Y, Kessler J A
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461.
J Neurochem. 1993 Jan;60(1):145-52. doi: 10.1111/j.1471-4159.1993.tb05832.x.
The intracellular mechanisms through which two trophic factors, ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), regulate cholinergic development were examined in sympathetic neuron cultures. Treatment with CNTF or LIF increased levels of choline acetyltransferase (ChAT) activity by 375 and 350%, respectively. However, in neuronal cultures depleted of protein kinase C (PKC) activity by chronic phorbol ester treatment, neither CNTF nor LIF elevated ChAT activity. Further, the stimulation of ChAT due to increased cell density was not observed in PKC-depleted sympathetic neurons. The inhibition of CNTF-stimulated ChAT by phorbol ester occurred in a dose-dependent manner and chronic phorbol ester treatments did not alter the levels of the catecholamine biosynthetic enzyme tyrosine hydroxylase. Moreover, increased levels of diacylglycerol, an endogenous activator of PKC, were observed in sympathetic neurons treated with CNTF. However, neither CNTF nor LIF stimulated the hydrolysis of phosphatidylinositol 4,5-bisphosphate. These observations suggest that a common PKC-dependent pathway, which is independent of phosphatidylinositol 4,5-bisphosphate hydrolysis, mediates the cholinergic stimulating effects of CNTF, LIF, and cell-cell contact in cultured sympathetic neurons.
在交感神经元培养物中研究了两种营养因子，睫状神经营养因子（CNTF）和白血病抑制因子（LIF）调节胆碱能发育的细胞内机制。用CNTF或LIF处理分别使胆碱乙酰转移酶（ChAT）活性水平提高了375%和350%。然而，在通过慢性佛波酯处理使蛋白激酶C（PKC）活性耗尽的神经元培养物中，CNTF和LIF均未提高ChAT活性。此外，在PKC耗尽的交感神经元中未观察到由于细胞密度增加对ChAT的刺激作用。佛波酯对CNTF刺激的ChAT的抑制呈剂量依赖性，慢性佛波酯处理并未改变儿茶酚胺生物合成酶酪氨酸羟化酶的水平。此外，在用CNTF处理的交感神经元中观察到二酰基甘油（PKC的内源性激活剂）水平升高。然而，CNTF和LIF均未刺激磷脂酰肌醇4,5-二磷酸的水解。这些观察结果表明，一条独立于磷脂酰肌醇4,5-二磷酸水解的常见PKC依赖性途径介导了CNTF、LIF和细胞间接触在培养的交感神经元中对胆碱能的刺激作用。
