In-vitro responses to ascorbate and manganese in fibroblasts from a patient with prolidase deficiency and iminodipeptiduria: cell growth, prolidase activity and collagen metabolism

Abstract

After successful ascorbate and manganese treatment of a female patient with prolidase deficiency and iminodipeptiduria, we attempted to explain the mechanism of action of these drugs in vitro, using them preferentially on skin fibroblasts. Since in vivo, ascorbate and manganese seemed to be responsible for both biochemical and clinical improvement, they were also expected to activate prolidase activity in vitro. Cell growth and prolidase activity were accordingly observed in fibroblast cultures supplemented with these compounds. It seemed that only ascorbate accounted for the successful in vivo response. To understand the mechanism involved, we studied collagen metabolism and found a decreased proline pool, a massive increase of rapidly degraded collagen and moderate enhancement of type III collagen and type I trimer in the patient's fibroblasts. We believe that ascorbate allowed the prolidase-deficient cells to maintain a normal collagen pool by increasing collagen synthesis. Both the massive increase in cell growth in response to ascorbate and the bad response as regards the quality of the collagen produced confirm the secondary nature of this mechanism. However, the relationship between accelerated collagen catabolism and prolidase deficiency remains unclear.