Ovine ceroid-lipofuscinosis. I: Lipopigment composition is indicative of a lysosomal proteinosis.
Ovine ceroid-lipofuscinosis. I: Lipopigment composition is indicative of a lysosomal proteinosis.
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绵羊蜡质脂褐质沉着症。
DOI：
10.1002/ajmg.1320310618
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Jolly,RD
中科院分区：
文献类型：
--
作者：
Palmer,DN;Martinus,RD;Barns,G;Reeves,RD;Jolly,RD
蜡样脂褐质沉积症是儿童和动物的遗传性溶酶体沉积病，其特征是荧光脂色素储存在各种组织中。脂质代谢缺陷或脂质过氧化控制已被假定来解释其发病机制，但潜在的生化缺陷仍然是未知的。在本研究中，脂色素是从患有蜡样脂肪褐质沉积症的绵羊的肝脏、肾脏、胰腺和脑中分离出来的。大约三分之二的脂肪色素质量是蛋白质。十二烷基硫酸钠聚丙烯酰胺凝胶电泳显示主要多肽带Mr为14，800，异质性多肽在5，000 - 9，000 Mrand主要多肽带Mr为3，500。这些不是正常的溶酶体蛋白。~（125）I标记研究表明，它们占胰腺脂肪色素质量的47%，其中3,500 M多肽单独占26%。脂色素多肽不是由二硫键连接在一起的较大蛋白质的亚基。在整个受影响组织匀浆中存在3，500个Mr蛋白，将其与正常组织匀浆区分开来。脂色素磷脂与正常溶酶体磷脂是相同的种类，包括双（单酰基甘油）磷酸，一种溶酶体标记物。同样，中性脂质，特别是长萜醇，泛醌和长萜酯是典型的溶酶体膜。脂色素含有1-1.7%的金属。对它们的分析表明脂肪色素的功能性溶酶体来源。得出的结论是，低Mr蛋白特异性储存在绵羊蜡样-脂褐质沉积症中，并且该疾病是溶酶体蛋白沉积症。
The ceroid‐lipofuscinoses are inherited lysosomal storage diseases of children and animals characterised by a fluorescent lipopigment stored in a variety of tissues. Defects in lipid metabolism or the control of lipid peroxidation have been postulated to explain their pathogenesis but the underlying biochemical defect is still unknown.In the present study lipopigment was isolated from liver, kidney, pancreas and brain of sheep affected with ceroid‐lipofuscinosis. Approximately two‐thirds of the lipopigment mass was protein. Sodium dodecyl sulphate polyacrylamide gel electrophoresis showed a major polypeptide band of Mr14,800, heterogeneous polypeptides between 5,000–9,000 Mrand a major band of Mr3,500. These were not normal lysosomal proteins. I125radiolabeling studies indicated that they were 47% of the pancreatic lipopigment mass, the 3,500 Mrpolypeptides alone accounting for 26%. Lipopigment polypeptides were not subunits of a larger protein held together by disulphide bonds. The presence of the 3,500 Mrproteins in whole affected tissue homogenates distinguished them from homogenates of normal tissues.Lipopigment phospholipids were the same species as normal lysosomal phospholipids, including bis (monoacylglycero) phosphate, a lysosomal marker. Similarly the neutral lipids, notably dolichol, ubiquinone and dolichyl esters were typical of those in lysosomal membranes. Lipopigments contained 1–1.7% metals. Analyses of them indicated a functional lysosomal origin for the lipopigment. It was concluded that low Mrproteins are specifically stored in ovine ceroid‐lipofuscinosis and that this disease is a lysosomal proteinosis.