脯氨酸羟化酶抑制剂

Research progress of proline hydroxylase inhibitors

缺氧诱导因子(hypoxia inducible factor,HIF)是缺氧反应的关键调节因子,其特定脯氨酸残基被脯氨酸羟化酶(proline hydroxylase,PHD)羟基化后即通过泛素途径降解。PHD抑制剂(proline hydroxylase inhibitor,PHI)通过抑制泛素降解途径使HIF免受降解,从而稳定HIF蛋白。因此,PHI可以参与调控HIF介导的下游基因表达,如促红细胞生成素及血管内皮生长因子表达,继而发挥重要的生物学效应,在科研和临床上显示出极大的应用价值。

Hypoxia inducible factor （HIF） is a key modulator in hypoxia. The hydroxylation of specific proline residues of HIF by proline hydroxylase （PHD） plays a critical role in degrading HIF through the ubiquitin-proteasome pathway. PHD inhibitors （PHI） can stabilize HIF by inhibiting the degradation reaction of HIF protein. Therefore, PHI takes part in the regulation of the expression of down-stream targeted genes of HIF, such as EPO and VEGF, thus exerting important biological functions and showing great application value both in research and clinical fields. Here in the paper we review the research progress of proline hydroxylase inhibitors.