Recessive dystrophic epidermolysis bullosa: evidence for an altered collagenase in fibroblast cultures.
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.
D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004820:Epidermolysis Bullosa / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D003012:Microbial Collagenase / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000201:enzymology*
D003012:Microbial Collagenase; D002118:Calcium