Williams M L, Rutherford S L, Feingold K R
Dermatology, Service, Veterans Administration Medical Center, San Francisco, CA.
J Lipid Res. 1987 Aug;28(8):955-67.
Effects of cholesterol sulfate on acetate incorporation into lipid fractions were examined in normal human fibroblast and keratinocyte cultures. Inhibition of sterologenesis in normal fibroblast cultures by cholesterol sulfate was less profound than that produced by either lipoprotein-containing serum or 25-hydroxycholesterol. Cholesterol sulfate also inhibited sterologenesis in low density lipoprotein receptor-deficient fibroblasts and inhibited both sterologenesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in keratinocytes. Cholesterol sulfate increased incorporation of acetate into fatty acid-containing lipids in preconfluent cultures of both cell types in lipoprotein-depleted media. Similar effects were not observed either in response to lipoprotein-containing serum or 25-hydroxycholesterol. Cholesterol sulfate had no effect on oleic acid incorporation into diglycerides, triglycerides, or phospholipid fractions; neither did it inhibit acid lipase activity; nor did it inhibit fatty acid oxidation, indicating that cholesterol sulfate does not inhibit catabolism of acyl lipids. Because cholesterol sulfate had similar effects on fatty acid metabolism in steroid sulfatase-deficient fibroblasts lines, desulfation to cholesterol is not a prerequisite. Cholesterol sulfate did not significantly affect incorporation of oleic acid into sterol esters in fibroblast cultures, but in contrast, inhibited sterol esterification in keratinocyte cultures. These data suggest a novel role for cholesterol sulfate as a modulator of cellular lipid biosynthesis.
在正常人成纤维细胞和角质形成细胞培养物中研究了胆固醇硫酸酯对乙酸盐掺入脂质组分的影响。胆固醇硫酸酯对正常成纤维细胞培养物中甾醇生成的抑制作用不如含脂蛋白血清或25-羟基胆固醇所产生的抑制作用深刻。胆固醇硫酸酯还抑制低密度脂蛋白受体缺陷型成纤维细胞中的甾醇生成，并抑制角质形成细胞中的甾醇生成和3-羟基-3-甲基戊二酰辅酶A还原酶活性。在脂蛋白缺乏培养基中，两种细胞类型的预汇合培养物中，胆固醇硫酸酯增加了乙酸盐掺入含脂肪酸的脂质中。在对含脂蛋白血清或25-羟基胆固醇的反应中未观察到类似的效果。胆固醇硫酸酯对油酸掺入甘油二酯、甘油三酯或磷脂组分没有影响；它也不抑制酸性脂肪酶活性；也不抑制脂肪酸氧化，这表明胆固醇硫酸酯不抑制酰基脂质的分解代谢。由于胆固醇硫酸酯对类固醇硫酸酯酶缺陷型成纤维细胞系中的脂肪酸代谢有类似影响，因此脱硫为胆固醇不是必需的。胆固醇硫酸酯对成纤维细胞培养物中油酸掺入甾醇酯没有显著影响，但相反，它抑制角质形成细胞培养物中的甾醇酯化。这些数据表明胆固醇硫酸酯作为细胞脂质生物合成调节剂具有新作用。
