Juvenile and adult metachromatic leukodystrophy: partial restoration of arylsulfatase A (cerebroside sulfatase) activity by inhibitors of thiol proteinases.
Juvenile and adult metachromatic leukodystrophy: partial restoration of arylsulfatase A (cerebroside sulfatase) activity by inhibitors of thiol proteinases.
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青少年和成人异染性脑白质营养不良：硫醇蛋白酶抑制剂部分恢复芳基硫酸酯酶 A（脑苷脂硫酸酯酶）活性。
DOI：
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发表时间：
1983
影响因子：
11.1
通讯作者：
Andrej Hasilik
中科院分区：
文献类型：
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作者：
K. Figura;F. Steckel;Andrej Hasilik
用代谢标记法和免疫沉淀法对1例幼年异色性脑白质营养不良和3例成人脑白质营养不良患者的成纤维细胞培养的芳基硫酸酯酶A多肽进行了检测。突变细胞中的芳基硫酸酯酶多肽严重缺乏。然而，根据在10 mM NH4Cl存在下孵育的细胞的多肽分泌或活性估计的表观合成速度是对照组的20%-50%。在没有NH4Cl的情况下，突变酶在转运到溶酶体内后迅速降解。在硫醇蛋白水解酶抑制剂的存在下，芳基硫酸酯酶A多肽的降解得到部分保护，催化活性增强。此外，治疗部分纠正了细胞降解脑苷硫酸盐的能力。在异色性脑白质营养不良的变种中，硫醇蛋白水解酶的抑制剂可能具有治疗价值，在这种异色性脑白质营养不良中合成了不稳定的芳基硫酸酯酶A。
Arylsulfatase A polypeptides were examined in cultured fibroblasts from a patient with juvenile metachromatic leukodystrophy and three patients with the adult form of the disease, with the aid of metabolic labeling and immunoprecipitation. The mutant cells were severely deficient in the arylsulfatase polypeptides. The apparent rate of synthesis, however, as estimated from the secretion of polypeptides or activity by cells incubated in the presence of 10 mM NH4Cl was 20-50% of control. In the absence of NH4Cl, the mutant enzyme was rapidly degraded upon transport into lysosomes. In the presence of inhibitors of thiol proteinases arylsulfatase A polypeptides were partially protected from degradation, and the catalytic activity of arylsulfatase A was increased. In addition, the treatment partially corrected the capacity of the cells to degrade cerebroside sulfates. Inhibitors of thiol proteinases may be of therapeutic value in variants of metachromatic leukodystrophy, in which an unstable arylsulfatase A is synthesized.