Qian J J, Duncan B, Adzick N S, Bhatnagar R S
Laboratory of Connective Tissue Biochemistry, School of Dentistry, University of California, San Francisco 94143-0424.
Cell Mol Biol Res. 1993;39(5):525-33.
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.
虽然众所周知，在抗坏血酸存在的情况下细胞脯氨酰羟化酶活性会增加，但这种调节机制尚未完全了解。已知抗坏血酸会产生活性氧自由基，这些自由基通过涉及细胞核中多聚ADP-核糖合成的机制参与基因表达的调控。我们研究了这种机制在调节人胎儿（20周）和新生儿（包皮）真皮成纤维细胞以及IMR-90成纤维细胞培养物中脯氨酰羟化酶活性方面的可能作用。在抗坏血酸盐存在的情况下，这些细胞中脯氨酰羟化酶的活性增加。抗坏血酸盐显著提高了多聚ADP-核糖合成酶的水平。多聚ADP-核糖合成抑制剂可消除或降低脯氨酰羟化酶活性的增加。我们的研究表明，抗坏血酸盐可能通过激活涉及多聚ADP-核糖的表观遗传控制机制来调节脯氨酰羟化酶的细胞活性。
