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

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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.