Reduction of GTP Cyclohydrolase I Feedback Regulating Protein Expression by Hydrogen Peroxide in Vascular Endothelial Cells

Abstract

We examined the effect of H₂O₂ on the expression of GTP cyclohydrolase I (GTPCH) feedback regulating protein (GFRP). Addition of H₂O₂ to endothelial cells decreased GFRP mRNA levels, in contrast to the increase of tetrahydrobiopterin (BH₄) content and GTPCH mRNA levels. The inhibitors of nitric oxide (NO) synthase and GTPCH had no influence on the decrease of GFRP mRNA levels in H₂O₂-treated cells. It is suggested that H₂O₂ induces BH₄ synthesis through not only induction of GTPCH but also reduction of GFRP. The decrease of GFRP mRNA level appears to be independent of the produced NO and BH₄.