Recessive dystrophic epidermolysis bullosa: evidence for an altered collagenase in fibroblast cultures.
Recessive dystrophic epidermolysis bullosa: evidence for an altered collagenase in fibroblast cultures.
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隐性营养不良性大疱性表皮松解症：成纤维细胞培养物中胶原酶改变的证据。
DOI：
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发表时间：
1977
影响因子：
11.1
通讯作者：
E. Bauer
中科院分区：
文献类型：
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作者：
E. Bauer
胶原酶与隐性营养不良性大疱性表皮病水疱形成的发病机制有关。为了检查这种酶中的畸变是否在疾病中是重要的，来自两个患者的成纤维细胞培养物被用于比较来自突变细胞的胶原酶的性质与来自对照成纤维细胞系的胶原酶的性质。从突变体成纤维细胞纯化的胶原原酶制剂在低Ca2+浓度下比对照酶显着更热不稳定。它们还表现出对Ca2+的亲和力降低，Ca2+是酶活性和热稳定性所需的辅因子。此外，来自每个突变系的胶原酶显示出比活性降低，表示为每单位免疫反应蛋白的活性，其中一名患者的酶平均值为对照的39%，另一名患者的酶平均值为对照的16%。这些数据支持这样的假设，即在这两个患者中，改变的胶原酶是结构基因突变、酶的翻译后修饰缺陷或调节胶原酶正常降解的基因突变的结果。
Collagenase has been implicated in the pathogenesis of blister formation in recessive dystrophic epidermolysis bullosa. In order to examine whether aberrations in this enzyme are important in the disease, fibroblast cultures from two patients were used to compare the properties of the collagenases from the mutant cells with those from control fibroblast lines. Purified procollagenase preparations from the mutant fibroblasts were significantly more thermolabile at low Ca2+ concentration than control enzymes. They also showed a decrease in affinity for Ca2+, a cofactor required both for enzyme activity and thermal stability. In addition, the collagenase from each mutant line displayed diminished specific activity, expressed as activity per unit of immunoreactive protein, with a mean value of 39% of control for one patient's enzyme and 16% for the other. The data support the postulate that, in these two patients, the altered collagenase is the result of a structural gene mutation, a defect in the post-translational modification of the enzyme, or a mutation in a gene regulating the normal degradation of collagenase.