Decreased procollagen production in cultured fibroblasts from patients with Lowe's syndrome.
The oculo-cerebro-renal syndrome described by Lowe is a catastrophic disease in children characterized by progressive eye, central nervous system and kidney degeneration. We determined procollagen production in cultured skin fibroblasts originating from patients with Lowe's syndrome as well as normal individuals after incubation of cells with [14C]proline for 1,4 and 20 h. Using [14C]hydroxyproline formation, in relation to cell protein or DNA, as an index of procollagen production, we found that cultured cells from patients synthesized collagenous protein at a substantially reduced level. This decrease in synthesis in cultured fibroblasts from patients could not be accounted for by differences in the specific radioactivity of the free intracellular proline; moreover, it could not be attributed to differences in the kinetics of growth between normal and affected cell lines. The degree of hydroxylation of proline residues in collagen was the same in both normal and affected cells.
D002478:Cells, Cultured; D005347:Fibroblasts; D006801:Humans; D006909:Hydroxyproline / Q000096:biosynthesis; D009800:Oculocerebrorenal Syndrome / Q000378:metabolism*; D011347:Procollagen / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D015499:Renal Tubular Transport, Inborn Errors / Q000378:metabolism*
D011347:Procollagen; D006909:Hydroxyproline