Stait S E, Leake D S
School of Animal and Microbial Sciences, University of Reading, Whiteknights, Berks, U.K.
Biochem J. 1996 Dec 1;320 ( Pt 2)(Pt 2):373-81. doi: 10.1042/bj3200373.
Ascorbate at concentrations of 60-100 microM inhibits the modification of freshly prepared low-density lipoprotein (LDL) by macrophages. With 'moderately oxidized' LDL (produced by prolonged storage in a refrigerator), however, ascorbate does not inhibit LDL modification by macrophages and actually modifies the LDL itself in the absence of macrophages [Stait and Leake (1994) FEBS Lett. 341, 263-267]. We have now shown that dehydroascorbate can modify both 'fresh' LDL and moderately oxidized LDL in a dose-dependent manner to increase its uptake by macrophages. The modification of moderately oxidized LDL by ascorbate and dehydroascorbate or of 'fresh' LDL by dehydroascorbate is dependent on the presence of iron or copper. In 'fresh' LDL, ascorbate inhibited conjugated-diene formation by copper. In moderately oxidized LDL, the number of conjugated dienes present was decreased rapidly in the presence of copper and ascorbate. Dehydroascorbate decreased the lag phase and increased the rate of copper-induced conjugated-diene formation in 'fresh' LDL (although in some experiments it inhibited the formation of conjugated dienes). The ascorbate-modified moderately oxidized LDL was taken up by macrophages by their scavenger receptors, as the uptake was inhibited by polyinosinic acid or fucoidan. Ascorbate and dehydroascorbate therefore have the potential to increase LDL oxidation under certain conditions, but whether or not they do so in vivo is unknown.
浓度为60 - 100微摩尔的抗坏血酸盐可抑制巨噬细胞对新制备的低密度脂蛋白（LDL）的修饰。然而，对于“中度氧化”的LDL（通过在冰箱中长时间储存产生），抗坏血酸盐并不抑制巨噬细胞对LDL的修饰，实际上在没有巨噬细胞的情况下它本身就能修饰LDL [Stait和Leake（1994年）《欧洲生物化学学会联合会快报》341, 263 - 267]。我们现已表明，脱氢抗坏血酸盐能够以剂量依赖的方式修饰“新鲜”LDL和中度氧化的LDL，从而增加巨噬细胞对其的摄取。抗坏血酸盐和脱氢抗坏血酸盐对中度氧化LDL的修饰或脱氢抗坏血酸盐对“新鲜”LDL的修饰依赖于铁或铜的存在。在“新鲜”LDL中，抗坏血酸盐抑制铜诱导的共轭二烯形成。在中度氧化的LDL中，在铜和抗坏血酸盐存在的情况下，共轭二烯的数量迅速减少。脱氢抗坏血酸盐缩短了“新鲜”LDL中铜诱导的共轭二烯形成的延迟期并增加了其形成速率（尽管在某些实验中它抑制了共轭二烯的形成）。抗坏血酸盐修饰的中度氧化LDL通过巨噬细胞的清道夫受体被巨噬细胞摄取，因为这种摄取被聚肌苷酸或岩藻依聚糖抑制。因此，抗坏血酸盐和脱氢抗坏血酸盐在某些条件下有可能增加LDL的氧化，但它们在体内是否会这样做尚不清楚。
