Schmitz G, Fischer H, Beuck M, Hoecker K P, Robenek H
Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität, Münster, FRG.
Arteriosclerosis. 1990 Nov-Dec;10(6):1010-9. doi: 10.1161/01.atv.10.6.1010.
The cellular defect in Tangier mononuclear phagocytes (MNP) was shown to be associated with significant abnormalities in cellular phospholipid, triglyceride, and cholesteryl ester metabolism by using various radiolabeled precursors (32Pi, 3H-serine, 3H-choline, 14C-acetate, and 14C-oleic acid). Tangier MNP expressed increased rates of synthesis for phospholipids (twofold), triglycerides (fivefold), and cholesteryl esters (threefold) as compared to normal MNP when incubated in McCoy's medium containing 0.2% human serum albumin. The turnover rate of cellular phospholipids was also enhanced, while the turnover rates for triglycerides and cholesteryl esters were normal, thus leading to the accumulation of a larger pool of labeled triglycerides and cholesteryl esters in Tangier MNP. The individual phospholipid classes, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine were similarly affected. Cholesterol loading led to approximately 30% down-regulation of phospholipid synthesis in normal cells, but Tangier MNP showed a smaller response. When nonloaded normal MNP were exposed to high density lipoprotein3 (HDL3), they diminished cellular cholesterol esterification mediated by acyl-CoA:cholesterol acyltransferase (ACAT); in Tangier MNP, ACAT activity increased in the presence of HDL3. When cholesterol-loaded normal and Tangier MNP were treated with HDL3, an up-regulation of phospholipid synthesis was observed in both cell types, but Tangier MNP showed a smaller response. We conclude that the defect in Tangier disease, which we recently described as a "disorder of intracellular traffic" (Schmitz et al. Proc Natl Acad Sci USA 1985;82:6305-6309), is associated with a dysregulation of cellular lipid metabolism, leading to an overproduction of triglycerides and esterified cholesterol and to enhanced synthesis and catabolism of phospholipids.
通过使用各种放射性标记前体（32Pi、3H-丝氨酸、3H-胆碱、14C-乙酸盐和14C-油酸），发现丹吉尔单核吞噬细胞（MNP）中的细胞缺陷与细胞磷脂、甘油三酯和胆固醇酯代谢的显著异常有关。与正常MNP相比，当在含有0.2%人血清白蛋白的 McCoy 培养基中孵育时，丹吉尔MNP的磷脂（两倍）、甘油三酯（五倍）和胆固醇酯（三倍）合成速率增加。细胞磷脂的周转率也增强，而甘油三酯和胆固醇酯的周转率正常，从而导致丹吉尔MNP中标记的甘油三酯和胆固醇酯池更大。各个磷脂类别，即磷脂酰胆碱、鞘磷脂、磷脂酰乙醇胺和磷脂酰丝氨酸受到类似影响。胆固醇加载导致正常细胞中磷脂合成下调约30%，但丹吉尔MNP的反应较小。当未加载的正常MNP暴露于高密度脂蛋白3（HDL3）时，它们减少了由酰基辅酶A：胆固醇酰基转移酶（ACAT）介导的细胞胆固醇酯化；在丹吉尔MNP中，HDL3存在时ACAT活性增加。当用HDL3处理加载胆固醇的正常和丹吉尔MNP时，两种细胞类型均观察到磷脂合成上调，但丹吉尔MNP的反应较小。我们得出结论，丹吉尔病的缺陷，我们最近将其描述为“细胞内运输障碍”（施密茨等人，《美国国家科学院院刊》1985年；82：6305 - 6309），与细胞脂质代谢失调有关，导致甘油三酯和酯化胆固醇的过度产生以及磷脂合成和分解代谢增强。
