Calandra S, Tarugi P, Battistini N, Ferrari R
Metabolism. 1979 Aug;28(8):843-50. doi: 10.1016/0026-0495(79)90211-7.
The present study investigated the effect of serum lipoproteins on sterol synthesis by isolated rat hepatocytes. These cells were maintained in culture medium for 24 hr and incubated for the same period of time with increasing concentrations of serum lipoproteins (5-150 microgram of lipoprotein-protein per ml) isolated from different animal species. The viability of the cells was ascertained by their ability to synthesize cholesterol and protein and to secrete serum proteins into the medium. Rat VLDL and LDL did not alter sterol synthesis, which was stimulated instead by HDL. Rat serum chylomicrons were also ineffective. Human LDL significantly reduced the synthesis of sterols from both acetate and tritiated water; this effect was also induced by human VLDL to a reduced extent. VLDL isolated from hypercholesterolemic rabbit (VLDLC) strongly inhibited sterol synthesis from acetate but not from mevalonate. Cholesteryl-ester-rich VLDL isolated from a patient with type III hyperlipidemia (type III VLDL) were more effective than normal VLDL in suppressing sterol synthesis from acetate. The implications of these findings are discussed with regard to the possible role of cholesteryl-ester-rich lipoproteins on the in vivo regulation of sterol synthesis in the liver.
本研究调查了血清脂蛋白对分离的大鼠肝细胞甾醇合成的影响。这些细胞在培养基中培养24小时,并与从不同动物物种分离的浓度不断增加的血清脂蛋白(每毫升5 - 150微克脂蛋白 - 蛋白)孵育相同的时间。通过细胞合成胆固醇和蛋白质以及将血清蛋白分泌到培养基中的能力来确定细胞的活力。大鼠极低密度脂蛋白(VLDL)和低密度脂蛋白(LDL)不会改变甾醇合成,相反,高密度脂蛋白(HDL)会刺激甾醇合成。大鼠血清乳糜微粒也没有效果。人LDL显著降低了从乙酸盐和氚化水合成甾醇的量;人VLDL也有这种作用,但程度较轻。从高胆固醇血症兔分离的VLDL(VLDLC)强烈抑制从乙酸盐合成甾醇,但不抑制从甲羟戊酸合成甾醇。从III型高脂血症患者分离的富含胆固醇酯的VLDL(III型VLDL)在抑制从乙酸盐合成甾醇方面比正常VLDL更有效。针对富含胆固醇酯的脂蛋白在肝脏中甾醇合成的体内调节中可能发挥的作用,对这些发现的意义进行了讨论。