Stimulation of Tetrahydrobiopterin Synthesis by Basic Fibroblast Growth Factor in Vascular Endothelial Cells

The purpose of this study was to examine whether basic fibroblast growth factor (bFGF) stimulates tetrahydrobiopterin (BH 4 ) synthesis in mouse brain microvascular endothelial cells. BH 4 content was determined by oxidation under acidic conditions as biopterin and analysed with reversed-phase high Performance liquid chromatography. Measurement of the mRNA level of QTP-cyclohydrolase I (GTPCH), which is the rate-limiting enzyme of the de novo pathway of BH 4 synthesis. The addition of bFGF to endothelial cells increased the BH 4 content and GTPCH mRNA levels in an incubation period- and a concentration-dependent manner. 2,4-Diamino-6- hydroxypyrimidine, an inhibitor of GTPCH, strongly reduced the bFGF-induced increase in BH 4 content. These findings suggest that bFGF stimulates BH 4 synthesis via a de novo pathway with the induction of GTPCH.