四氢生物蝶呤合成抑制剂对小鼠骨髓基质细胞增殖分化的影响

BH4 belongs to the aromatic amino acid hydroxylase coenzyme, and is an important cofactor for nitric oxide synthase. GTP cyclohydrolase I (GTPCH) is the rate-limiting enzyme of BH4 synthesis. DAHP is the inhibitor of GTPCH. The effect and mechanism of DAHP on proliferation and differentiation of op9 cells were explored by methyl thiazolyl tetrazolium (MTT) method. Oil red O staining and spectrophotography were applied to analyze the degree of differentiation. DAHP inhibited proliferation of op9 cells in a dose-dependent manner. Oil red O staining results showed that DAHP inhibited differentiation of op9 cells iEffect of BH4 synthesis inhibitors on the proliferation and differentiation of op9 cellsn the range of 500 μmol/L to 900 μmol/L. Real-time PCR was applied to detect the mRNA expression of related genes. The transcription level of GTPCH was decreased. Glycolysis, pentose phosphate pathway, phenylalanine metabolism, TCA cycle, and one carbon pool by folate were down-regulated through NADPH requlation, and all of which may explain why the differentiation of op9 cells was inhibited by DAHP. ?????