Regulation of prolyl hydroxylase by ascorbic acid is mediated by polyADP-ribose synthesis

While it is well known that cellular prolyl hydroxylase activity is increased in the presence of ascorbic acid, the mechanism of this modulation is not fully understood. Ascorbic acid is known to generate reactive oxygen radicals which are involved in the regulation of gene expression through mechanisms involving the synthesis of polyADP-ribose in the nucleus. We examined a possible role for this mechanism in modulating prolyl hydroxylase activity in cultures of human fetal (20 week) and neonatal (foreskin) dermal fibroblasts and IMR-90 fibroblasts. The activity of prolyl hydroxylase in these cells increased in the presence of ascorbate. Ascorbate markedly increased the levels of polyADP-ribose synthetase. The increase in prolyl hydroxylase activity was abolished or decreased by inhibitors of polyADP-ribose synthesis. Our studies suggest that ascorbate may regulate the cellular activity of prolyl hydroxylase by activating epigenetic control mechanisms involving polyADP-ribose.