Molecular basis for the inhibition of hypoxia-induced apoptosis by thymidine phosphorylase

血小板源性内皮细胞生长因子/胸苷磷酸化酶（PD-ECGF/TP）是一种血管生成因子，可刺激内皮细胞的趋化性，并对缺氧诱导的细胞凋亡具有抵抗作用。TP和2-脱氧d -核糖（TP酶活性降解胸苷的产物）抑制缺氧诱导的缺氧诱导因子（HIF） 1α的上调。我们研究了TP和2-脱氧-d核糖抑制HIF-1α上调的分子基础。缺氧条件下2-脱氧核糖增强HIF-1α与pVHL的相互作用。2-脱氧核糖不影响HIF-1α、脯氨酸羟化酶（PHD）1/2/3和VHL mRNA的表达。在缺氧条件下，2-脱氧- d核糖也增强了HIF-1α与PHD2的相互作用。HIF-1α与pVHL和PHD2增强相互作用的机制有待进一步研究。

An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. TP and 2-deoxy-D-ribode, a degradation product of thymidine generated by TP enzymatic activity, inhibited the upregulation of hypoxia-inducible factor (HIF) 1α induced by hypoxia. We investigated the molecular basis for the suppressive effect of TP and 2-deoxy-D-ribose on the upregulation of HIF-1α. 2-Deoxy-D-ribose enhanced interaction of HIF-1α and pVHL under hypoxic condition. 2-Deoxy-D-ribose did not affect the expression of HIF-1α, prolyl hydroxylase (PHD)1/2/3 and VHL mRNA. 2-Deoxy-D-ribose also enhanced interaction of HIF-1α and PHD2 under hypoxic condition. Further study is needed to elucidate the mechanism about the augmented interaction of HIF-1α with pVHL and PHD2.