Hall N A, Lake B D, Palmer D N, Jolly R D, Patrick A D
Department of Clinical Biochemistry, Institute of Child Health, London, England.
Adv Exp Med Biol. 1989;266:225-41; discussion 242. doi: 10.1007/978-1-4899-5339-1_16.
The ceroid-lipofuscinoses (CL) are a group of inherited diseases characterised by the accumulation, in brain, of autofluorescent storage cytosomes which have similar histochemical staining properties to lipofuscin, the neuronal wear and tear pigment of old-age brain. The storage cytosomes stain strongly with periodic acid-Schiff reagent (PAS), indicating the presence of carbohydrate. In brain from each childhood form of CL, concentrations of phosphorylated dolichol (Dol-P) are 10- to 20- fold higher than in age-matched controls. Brain Dol-P concentrations are also increased between 2 and 5- fold in several different lipidoses and in elderly subjects. Much of the Dol-P which accumulates is located within the storage cytosomes. Dol-P constitutes 2-3% of the dry weight of storage cytosomes from juvenile and late-infantile CL, and 0.3-0.7% of storage cytosomes from infantile CL, ovine CL and of lipofuscin isolated from old age brain. The bulk of the Dol-P in CL brain and in isolated storage cytosomes is present as dolichyl pyrophosphoryl oligosaccharides (Dol-PP-OS). The constitutions of the oligosaccharide moieties differ in the various forms of the disease. Histochemical analysis of frozen sections of unfixed brain after extraction by various lipid solvents indicates that the major part of the PAS positive intraneuronal material in CL brain and in old-age brain has the extraction properties of Dol-PP-OS. Carbohydrate represents 4-7% of the dry weight of CL storage cytosomes and of lipofuscin. The major monosaccharide components are mannose, N-acetyl glucosamine, glucose and galactose. Depending on the form of the disease studied, up to 40% of this material can be accounted for by Dol-PP-OS. Polyacrylamide gel electrophoresis of storage cytosomes followed by lectin blotting demonstrates several low molecular weight components which bind concanavalin A. These do not coelute with the major protein components and may well be Dol-PP-OS. We conclude that Dol-PP-OS are concentrated in storage cytosomes in CL and are one of their major glycoconjugate components.
蜡样脂褐质沉积症（CL）是一组遗传性疾病，其特征是大脑中出现自发荧光储存细胞体的积累，这些细胞体具有与脂褐质相似的组织化学染色特性，脂褐质是老年大脑中的神经元磨损色素。储存细胞体对过碘酸希夫试剂（PAS）染色强烈，表明存在碳水化合物。在CL的每种儿童期形式的大脑中，磷酸化多萜醇（Dol-P）的浓度比年龄匹配的对照组高10至20倍。在几种不同的脂质沉积症和老年受试者中，大脑Dol-P浓度也增加了2至5倍。积累的大部分Dol-P位于储存细胞体内。Dol-P占青少年和晚婴儿期CL储存细胞体干重的2-3%，占婴儿期CL、绵羊CL和从老年大脑中分离出的脂褐质储存细胞体干重的0.3-0.7%。CL大脑和分离出的储存细胞体中的大部分Dol-P以多萜醇焦磷酸寡糖（Dol-PP-OS）的形式存在。在疾病的各种形式中，寡糖部分的组成不同。用各种脂质溶剂提取后对未固定大脑的冰冻切片进行组织化学分析表明，CL大脑和老年大脑中PAS阳性神经元内物质的主要部分具有Dol-PP-OS的提取特性。碳水化合物占CL储存细胞体和脂褐质干重的4-7%。主要的单糖成分是甘露糖、N-乙酰葡糖胺、葡萄糖和半乳糖。根据所研究疾病的形式，这种物质的高达40%可由Dol-PP-OS解释。对储存细胞体进行聚丙烯酰胺凝胶电泳，然后进行凝集素印迹分析，显示出几种与伴刀豆球蛋白A结合的低分子量成分。这些成分与主要蛋白质成分不同时洗脱，很可能是Dol-PP-OS。我们得出结论，Dol-PP-OS集中在CL的储存细胞体中，是其主要糖缀合物成分之一。
