Volpe J J, Obert K A
J Neurochem. 1983 Feb;40(2):530-7. doi: 10.1111/j.1471-4159.1983.tb11315.x.
The relation of cellular cholesterol content of a biochemical expression of oligodendroglial differentiation was studied in cultured C-6 glial cells. Induction of the oligodendroglial marker enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase (CNP) was determined after alteration of the sterol content of cellular membranes by exposure to compactin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis. The sterol content and, as a consequence, the sterol/phospholipid molar ratio of C-6 glial cells were decreased by treating the cells, in 10% lipoprotein-poor serum, with various concentrations of compactin for 24 h. The degrees of sterol depletion thus produced were maintained for 48 h after removal of the compactin if the cells were maintained in serum-free medium, the culture conditions necessary for induction of CNF in untreated cells. Forty-eight hours after removal of serum, no induction of CNP occurred in cells previously treated with 0.5 micrograms/ml of compactin, whereas untreated cells exhibited a three- to fourfold increase in CNP activity. Intermediate degree of sterol depletion resulted in intermediate degrees of inhibition of the CNP induction. Moreover, the morphological expressions of glial differentiation observed in the untreated cells did not occur in the sterol-depleted cells. That the effect of compactin on the induction of CNP relates to depletion of sterol was indicated by the finding that when low-density lipoprotein was added to the compactin-treated cells, the induction of CNP, the morphological expressions of differentiation, and the sterol/phospholipid molar ratios were preserved. The degree of sterol depletion that totally prevented the induction of CNP had no effect on (Na+ R K+)-activated ATPase activity, total protein synthesis, and cell viability. The data define a critical role for sterol in oligodendroglial differentiation in this model system.
在培养的C-6神经胶质细胞中，研究了细胞胆固醇含量与少突胶质细胞分化生化表达之间的关系。通过暴露于洛伐他汀（一种3-羟基-3-甲基戊二酰辅酶A还原酶和胆固醇合成的特异性抑制剂）来改变细胞膜的甾醇含量后，测定少突胶质细胞标志物酶2':3'-环核苷酸3'-磷酸水解酶（CNP）的诱导情况。在含10%低脂蛋白血清的培养基中，用不同浓度的洛伐他汀处理C-6神经胶质细胞24小时，可降低细胞的甾醇含量，进而降低甾醇/磷脂摩尔比。如果将细胞维持在无血清培养基中（这是未处理细胞诱导CNF所需的培养条件），去除洛伐他汀后，由此产生的甾醇消耗程度可维持48小时。去除血清48小时后，先前用0.5微克/毫升洛伐他汀处理的细胞未发生CNP诱导，而未处理的细胞CNP活性增加了三到四倍。中等程度的甾醇消耗导致CNP诱导的抑制程度中等。此外，在未处理的细胞中观察到的神经胶质细胞分化的形态学表达在甾醇消耗的细胞中未出现。当向洛伐他汀处理的细胞中添加低密度脂蛋白时，CNP的诱导、分化的形态学表达以及甾醇/磷脂摩尔比得以保留，这一发现表明洛伐他汀对CNP诱导的影响与甾醇消耗有关。完全阻止CNP诱导的甾醇消耗程度对（Na+，K+）-激活的ATP酶活性、总蛋白质合成和细胞活力没有影响。这些数据确定了甾醇在该模型系统中少突胶质细胞分化中的关键作用。
