Angelin B
Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Sweden.
Biochem J. 1988 Oct 15;255(2):529-34.
The lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl-(HMG-) CoA reductase in cultured mouse peritoneal macrophages has been investigated. In contrast to what has been reported for other cells, HMG-CoA reductase activity is not suppressed by normal serum or by normal low density lipoproteins (LDL) from humans or dogs. Suppression of reductase activity occurred when cells were cultured in the presence of beta-migrating very low density lipoproteins (beta-VLDL) or LDL from hypercholesterolaemic dogs, or LDL modified by acetoacetylation. Human beta-VLDL from an atypical type III hyperlipoproteinaemic patient was also effective, as was apolipoprotein (apo) E-containing high density lipoproteins (HDL) from cholesterol-fed dogs (apo-E HDLc). The results indicate that cholesterol biosynthesis in mouse peritoneal macrophages is regulated by lipoprotein cholesterol entering via receptor-mediated endocytosis. Normal LDL were not effective because of the poor binding and uptake of these lipoproteins by the apo-B, E (LDL) receptor. Only beta-VLDL, apo-E HDLc, and hypercholesterolaemic LDL were avidly taken up by this receptor and were able to suppress HMG-CoA reductase. Acetoacetylated LDL were internalized via the acetyl-LDL (scavenger) receptor. Thus, mouse macrophages differ from human fibroblasts and smooth muscle cells in their physiological regulation of cholesterogenesis.
已对培养的小鼠腹腔巨噬细胞中脂蛋白介导的3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的调节进行了研究。与其他细胞的报道相反，正常血清或人及犬的正常低密度脂蛋白（LDL）不会抑制HMG-CoA还原酶活性。当细胞在β-迁移极低密度脂蛋白（β-VLDL）、高胆固醇血症犬的LDL或经乙酰乙酸化修饰的LDL存在下培养时，还原酶活性受到抑制。来自非典型III型高脂蛋白血症患者的人β-VLDL也有效，胆固醇喂养犬的含载脂蛋白（apo）E的高密度脂蛋白（HDL）（apo-E HDLc）也有效。结果表明，小鼠腹腔巨噬细胞中的胆固醇生物合成受通过受体介导的内吞作用进入的脂蛋白胆固醇调节。正常LDL无效，因为这些脂蛋白与载脂蛋白B、E（LDL）受体的结合和摄取较差。只有β-VLDL、apo-E HDLc和高胆固醇血症LDL能被该受体大量摄取，并能够抑制HMG-CoA还原酶。乙酰乙酸化LDL通过乙酰-LDL（清道夫）受体被内化。因此，小鼠巨噬细胞在胆固醇生成的生理调节方面与人类成纤维细胞和平滑肌细胞不同。
