6-formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation

The chemical property of 6-formylpterin and its biological functions were e xamined. Polarographic studies revealed that 6-formylpterin reacted with NA D(P)H and consumed oxygen. In contrast, other conjugated pterins, such as b iopterin and neopterin, showed no consumption of oxygen. The production ana lysis using high-performance liquid chromatography documented that 6-formyl pterin catalyzes the conversion from NADH to NAD. Electroparamagnetic reson ance spin trapping experiments demonstrated that this reaction is accompani ed with the generation of reactive oxygen species (ROS), superoxide anion a nd hydrogen peroxide, When 6-formylpterin was administered to HL-60 cells, intracellular ROS generation was observed and apoptosis was induced. In con trast, other conjugated pterins induced neither intracellular ROS generatio n nor apoptosis in HL-60 cells. The intracellular ROS generation by 6-formy lpterin was observed in other cells, such as PanC-1 cells and Jurkat cells. 6-formylpterin suppressed cell proliferation in PanC-1 cells and inhibited Fas-mediated apoptosis in Jurkat cells. These findings indicate that, amon g conjugated pterins, 6-formylpterin has the unique property to transfer el ectron from NAD(P)H to oxygen and that the property brings about intracellu lar ROS generation, which exerts various biological functions such as induc tion of apoptosis, suppression of cell proliferation, and inhibition of Fas -mediated apoptosis. (C) 2001 Elsevier Science Inc.