Lund E, Andersson O, Zhang J, Babiker A, Ahlborg G, Diczfalusy U, Einarsson K, Sjövall J, Björkhem I
Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge Hospital Sweden, Stockholm, Sweden.
Arterioscler Thromb Vasc Biol. 1996 Feb;16(2):208-12. doi: 10.1161/01.atv.16.2.208.
We have recently demonstrated that cultured human alveolar macrophages efficiently convert cholesterol into excretable 27-oxygenated products. We show here that increasing the intracellular concentration of cholesterol by a factor of 10 leads to about a twofold increase in the excretion of 27-oxygenated products from cultured macrophages. Inhibition of the sterol 27-hydroxylase caused a significant intracellular accumulation of cholesterol. A direct comparison was made between flux of cholesterol and 27-oxygenated products from macrophages preloaded with [4-14C]cholesterol. Under the specific conditions employed with fetal calf serum in the culture medium, the flux of 27-oxygenated products was about 10% of that of cholesterol. Since the sterol 27-hydroxylase, which converts cholesterol to 27-oxygenated products, is present in many cell types, we suggest that 27-oxygenation is a general mechanism for removal of intracellular cholesterol. To evaluate this hypothesis, we measured the net uptake by the human liver of circulating 27-oxygenated products, which was found to be about 20 mg/24 h. This uptake corresponds to approximately 4% of the bile acid production, assuming quantitative conversion into bile acids. It is concluded that the 27-hydroxylase pathway is of significance for elimination of extrahepatic cholesterol.
我们最近证明，培养的人肺泡巨噬细胞能有效地将胆固醇转化为可排泄的27-氧化产物。我们在此表明，将细胞内胆固醇浓度提高10倍会导致培养的巨噬细胞中27-氧化产物的排泄量增加约两倍。抑制甾醇27-羟化酶会导致胆固醇在细胞内大量积累。对预先加载了[4-¹⁴C]胆固醇的巨噬细胞中胆固醇和27-氧化产物的通量进行了直接比较。在培养基中使用胎牛血清的特定条件下，27-氧化产物的通量约为胆固醇通量的10%。由于将胆固醇转化为27-氧化产物的甾醇27-羟化酶存在于许多细胞类型中，我们认为27-氧化是细胞内胆固醇清除的一种普遍机制。为了评估这一假设，我们测量了人肝脏对循环中27-氧化产物的净摄取量，发现约为20 mg/24 h。假设定量转化为胆汁酸，这种摄取量约占胆汁酸产生量的4%。结论是，27-羟化酶途径对肝外胆固醇的清除具有重要意义。
