Inhibitory effect of 6-formylpterin on HIF-1α protein accumulation

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a main regulator of metabolic adaptation to hypoxia. HIF-1α is induced by hypoxia, or by hypoxia-mimicking reagents, such as desferrioxamine (DFX), under a normoxic condition. A xanthine oxidase inhibitor, 6-formylpterin (6FP), is reported to exert its functions on reactive oxygen species (ROS) modulation. In this study, we investigated the effect of 6FP on HIF-1α expression under a DFX-treated or hypoxic condition. 6FP decreased HIF-1α expression at the protein level, but not at the mRNA level, in a dose-dependent manner, and this suppressive effect was reversed by the antioxidant, N-acetyl-L-cysteine (NAC). Furthermore, the ROS generated by 6FP was reversed with NAC coincubation. These findings suggest that intracellular ROS generated by 6FP decreased the HIF-1α protein accumulation under a DFX-treated or hypoxic condition. © 2007 Pharmaceutical Society of Japan.