Coetzee G A, Stein O, Stein Y
Atherosclerosis. 1979 Mar;32(3):277-87. doi: 10.1016/0021-9150(79)90171-0.
Human skin fibroblasts in culture were incubated for 48 h with 125I-labelled low density lipoprotein and chloroquine in the presence and absence of sodium ascorbate. Pretreatment of the cells for 3 days with sodium ascorbate and addition of the vitamin during incubation resulted in a decrease in cellular retention and an increase in degradation of the labelled low density lipoprotein. Similar results were obtained when the cells were pretreated for 3 days but the vitamin was not added during the final 48 h of incubation. Pretreatment of the cells with dithiothreitol, butylated hydroxy-toluene, beta-mercaptoethanol and D-alpha-tocopherol had a similar effect to that of ascorbate, i.e. reduction in low density lipoprotein retention and increase in degradation. Neither ascorbate nor the other reducing agents affected low density lipoprotein catabolism in control cells not treated with chloroquine. Sodium ascorbate pretreatment resulted also in a slight but significant alleviation of the chloroquine-induced inhibition of hydrolysis of cholesterol linoleate. It is proposed that sodium ascorbate by virtue of its reducing properties provides some protection to the intralysosomal hydrolases against the inhibitory action of chloroquine. If cholesterol accumulation in human and experimental atheroma is caused by partial inhibition of lysosomal enzymes, sodium ascorbate could play a role in the alleviation of such an inhibition.
将培养的人皮肤成纤维细胞在存在和不存在抗坏血酸钠的情况下,与125I标记的低密度脂蛋白和氯喹一起孵育48小时。用抗坏血酸钠对细胞进行3天预处理并在孵育期间添加该维生素,导致细胞对标记的低密度脂蛋白的摄取减少,降解增加。当细胞预处理3天但在孵育的最后48小时不添加该维生素时,获得了类似的结果。用二硫苏糖醇、丁基化羟基甲苯、β-巯基乙醇和D-α-生育酚对细胞进行预处理,其效果与抗坏血酸类似,即低密度脂蛋白摄取减少,降解增加。抗坏血酸和其他还原剂均不影响未用氯喹处理的对照细胞中的低密度脂蛋白分解代谢。抗坏血酸钠预处理还导致氯喹诱导的胆固醇亚油酸酯水解抑制作用略有但显著减轻。有人提出,抗坏血酸钠凭借其还原特性为溶酶体内水解酶提供了一定保护,使其免受氯喹的抑制作用。如果人和实验性动脉粥样硬化中的胆固醇积累是由溶酶体酶的部分抑制引起的,抗坏血酸钠可能在减轻这种抑制方面发挥作用。