DISTRIBUTION OF SAPOSIN PROTEINS (SPHINGOLIPID ACTIVATOR PROTEINS) IN LYSOSOMAL STORAGE AND OTHER DISEASES
DISTRIBUTION OF SAPOSIN PROTEINS (SPHINGOLIPID ACTIVATOR PROTEINS) IN LYSOSOMAL STORAGE AND OTHER DISEASES
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DOI：
10.1073/pnas.87.9.3493
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
KISHIMOTO, Y
中科院分区：
文献类型：
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作者：
MORIMOTO, S;YAMAMOTO, Y;KISHIMOTO, Y
鞘脂激活蛋白（A、B、C和D）是通过特异性溶酶体水解酶水解鞘脂所需的小的糖蛋白。这些saposins在脑，肝，脾从正常人以及患者与溶酶体贮积症的浓度进行了测定。对鞘脂激活蛋白A、C和D使用定量HPLC方法，对鞘脂激活蛋白B使用刺激测定。在正常组织中，saposin D是四种saposins中最丰富的。在Tay-Sachs病和婴儿Sandhoff病患者的脑中发现大量的saposins，尤其是saposin A（约为正常值的80倍）。在成年戈谢病患者的脾脏中，saposin A和D的积累（分别为正常的60倍和170倍）高于saposin C（约为正常的16倍）。在岩藻糖苷沉积症患者的肝脏中发现了类似的saposins A和D的大量积累（分别是正常的70倍和20倍）。鞘脂激活蛋白D是尼曼-皮克病患者肝脏中储存的主要鞘脂激活蛋白（约为正常值的30倍）。鞘脂激活素B和D的中度增加，发现在与GM 1神经节苷脂沉积症的患者。在Krabbe病、异染性脑白质营养不良、Fabry病、肾上腺脑白质营养不良、I细胞病、2型和3B型粘多糖样变性或Jansky-Bielschowsky病患者中发现所有saposins的正常或接近正常水平。在这些疾病的saposins的存储的影响进行了讨论。
Saposins (A, B, C, and D) are small glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Concentrations of these saposins in brain, liver, and spleen from normal humans as well as patients with lysosomal storage disease were determined. A quantitative HPLC method was used for saposin A, C, and D and a stimulation assay was used for saposin B. In normal tissues, saposin D was the most abundant of the four saposins. Massive accumulations of saposins, especially saposin A (about 80-fold increase over normal), were found in brain of patients with Tay-Sachs disease or infantile Sandhoff disease. In spleen of adult patients with Gaucher disease, saposin A and D accumulations (60- and 170-fold, respectively over normal) were higher than that of saposin C (about 16-fold over normal). Similar massive accumulations of saposins A and D were found in liver of patients with fucosidosis (about 70- and 20-fold, respectively, over normal). Saposin D was the primary saposin stored in the liver of a patient with Niemann-Pick disease (about 30-fold over normal). Moderate increases of saposins B and D were found in a patient with GM1 gangliosidosis. Normal or near normal levels of all saposins were found in patients with Krabbe disease, metachromatic leukodystrophy, Fabry disease, adrenoleukodystrophy, I-cell disease, mucopolysaccharidosis types 2 and 3B, or Jansky-Bielschowsky disease. The implications of the storage of saposins in these diseases are discussed.