Shah S N, Johnson R C
Department of Psychiatry, University of California, Eldridge 95431.
J Neurochem. 1988 May;50(5):1529-36. doi: 10.1111/j.1471-4159.1988.tb03040.x.
Cells dissociated from brains of 1-day-old rats were cultured in medium containing either lipoprotein-deficient serum (LPDS) or LPDS plus various lipoprotein fractions. Increases in number of cells and in DNA content served as a measure of cell growth. Cholesterol synthesis was measured from the incorporation of [14C]acetate into total nonsaponifiable lipids and digitonin-precipitable sterols, and from the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. The data indicated that cholesterol biosynthesis from acetate was reduced in cells cultured in medium containing either LPDS plus low-density lipoproteins (LDL), high-density lipoproteins (HDL), or total lipoproteins (LP) and that this reduction was accompanied by a reduction in the activity of the HMG CoA reductase and an increase in the esterified sterol content. The reduction in cholesterol synthesis from acetate was maximal in cells cultured in the presence of HDL, whereas the maximal reduction in the activity of HMG CoA reductase occurred in cells cultured in the presence of LP. The presence of LDL or LP in the culture medium enhanced the cell growth but the presence of HDL did not. Esterified sterol content was highest in cells cultured in the medium containing LPDS plus LP and was not detected in cells cultured in LPDS medium. It is inferred from these data that rat brain glial cells in culture are able to utilize cholesterol in lipoproteins, that the presence of LDL in the medium enhances cell growth, and that reduced cholesterol synthesis in the presence of lipoproteins may occur at the HMG CoA reductase step as well as at some other step(s).
从1日龄大鼠脑中分离出的细胞,在含有脂蛋白缺乏血清(LPDS)或LPDS加各种脂蛋白组分的培养基中培养。细胞数量和DNA含量的增加作为细胞生长的指标。通过[14C]乙酸掺入总非皂化脂质和洋地黄皂苷可沉淀甾醇的量,以及通过3-羟基-3-甲基戊二酰辅酶A(HMG CoA)还原酶的活性来测定胆固醇合成。数据表明,在含有LPDS加低密度脂蛋白(LDL)、高密度脂蛋白(HDL)或总脂蛋白(LP)的培养基中培养的细胞中,乙酸生成胆固醇的生物合成减少,并且这种减少伴随着HMG CoA还原酶活性的降低和酯化甾醇含量的增加。在HDL存在下培养的细胞中,乙酸生成胆固醇的合成减少最大,而HMG CoA还原酶活性的最大降低发生在LP存在下培养的细胞中。培养基中LDL或LP的存在促进细胞生长,但HDL的存在则不然。在含有LPDS加LP的培养基中培养的细胞中酯化甾醇含量最高,而在LPDS培养基中培养的细胞中未检测到。从这些数据推断,培养的大鼠脑胶质细胞能够利用脂蛋白中的胆固醇,培养基中LDL的存在促进细胞生长,并且脂蛋白存在下胆固醇合成的减少可能发生在HMG CoA还原酶步骤以及其他一些步骤。