REGULATION OF PROLYL HYDROXYLASE BY ASCORBIC-ACID IS MEDIATED BY POLYADP-RIBOSE SYNTHESIS

While it is well known that cellular prolyl hydroxylase activity is in creased in the presence of ascorbic acid, the mechanism of this modula tion is not fully understood. Ascorbic acid is known to generate react ive oxygen radicals which are involved in the regulation of gene expre ssion through mechanisms involving the synthesis of poly ADP-ribose in the nucleus. We examined a possible role for this mechanism in modula ting 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 presen ce of ascorbate. Ascorbate markedly increased the levels of poly ADP-r ibose synthetase. The increase in prolyl hydroxylase activity was abol ished or decreased by inhibitors of poly ADP-ribose synthesis. Our stu dies suggest that ascorbate may regulate the cellular activity of prol yl hydroxylase by activating epigenetic control mechanisms. involving poly ADP-ribose.