Defective processing of keratan sulfate in macular corneal dystrophy.
Defective processing of keratan sulfate in macular corneal dystrophy.
复制标题
黄斑角膜营养不良中硫酸角质素的加工缺陷。
DOI：
10.1016/s0021-9258(18)89809-x
复制
发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Jay H. Krachmer
中科院分区：
文献类型：
--
作者：
K. Nakazawa;John R. Hassell;V. C. Hascall;L. S. Lohmander;D. A. Newsome;Jay H. Krachmer
黄斑角膜营养不良是一种人类遗传性疾病，其特征在于角膜混浊，部分原因是未能合成成熟的硫酸角质素蛋白聚糖。在黄斑角膜和圆锥角膜，不涉及蛋白聚糖的异常，生物合成标记的大分子与[3 H]甘露糖和[14 C]葡糖胺在器官培养，和硫酸角质素蛋白聚糖免疫沉淀的抗体对猴硫酸角质素蛋白聚糖的蛋白质核心。硫酸软骨素蛋白聚糖，不与抗体反应，在患有黄斑角膜营养不良的患者的角膜中过度硫酸化。免疫沉淀物的表征表明，黄斑角膜不使硫酸角质素蛋白聚糖，但合成了免疫反应性糖蛋白，其量与圆锥角膜合成的硫酸角质素蛋白聚糖几乎相等。免疫沉淀的黄斑糖蛋白上的寡糖似乎是正常的。然而，大分子含有未硫酸化的糖缀合物，其几乎与从圆锥角膜硫酸角质素-蛋白聚糖分离的正常硫酸角质素链一样大，并且含有相同相对比例的标记葡萄糖胺、甘露糖和岩藻糖。这种糖缀合物对角蛋白酶的消化具有抗性。这些观察结果表明，黄斑角膜营养不良是由硫酸角质素合成错误引起的，可能涉及参与链的乳糖胺聚糖主链硫酸化的特定磺基转移酶。
Macular corneal dystrophy is a human genetic disorder characterized by corneal opacities that arise, in part, from a failure to synthesize mature keratan sulfate proteoglycans. The macromolecules in macular corneas and in keratoconus corneas, an abnormality not involving proteoglycans, were biosynthetically labeled with [3H]mannose and [14C]glucosamine in organ culture, and the keratan sulfate proteoglycans were immunoprecipitated with antibodies against the protein core of monkey keratan sulfate proteoglycan. The chondroitin sulfate proteoglycans, which did not react with the antibody, were oversulfated in corneas from patients with macular corneal dystrophy. Characterization of the immunoprecipitates showed that macular corneas did not make keratan sulfate proteoglycan but did synthesize an immunoreactive glycoprotein in nearly equal amounts as keratan sulfate proteoglycan was synthesized by the keratoconus cornea. The oligosaccharides on the immunoprecipitated macular glycoprotein appeared to be normal. However, the macromolecules contained an unsulfated glycoconjugate that was nearly as large as the normal keratan sulfate chains isolated from the keratoconus keratan sulfate-proteoglycan and contained the same relative proportions of labeled glucosamine, mannose, and fucose. This glycoconjugate was resistant to digestion with keratanase. These observations indicate that macular corneal dystrophy is caused by an error in the synthesis of keratan sulfate, possibly involving the specific sulfotransferases involved in sulfation of the lactosaminoglycan backbone of the chains.