Protective Effect of Tetrahydrobiopterin Against Reactive Oxygen Species- and Nitric Oxide-induced Vascular Endothelial Cell Injury

Abstract

Vascular endothelial cells are one of the major biological targets of reactive oxygen species (ROS) in ischemiareperfusion, diabetes, hypercholesterolemia and inflammation. Accumulated evidence has shown that tetrahydrobiopterin (BH4), which is an essential cefactor for nitric oxide synthase (NOS) activity, protected the cells against ROS and nitric oxide (NO) toxicities. Although NOS releases NO, which regulates vascular tone and immune surveillance under normal conditions, NOS also produces superoxide anion and hydrogen peroxide when BH4 is decreased, suggesting the possibility that NOS is a source of ROS under pathological conditions. Since BH4 is easily oxidized by ROS, oxidative stress may induce ROS release from NOS by the decomposition of BH4. BH4 also has an antioxidative activity and scavenging activity for ROS. In this review, the r o l e of BH4 in the function of' NOS, and the mechanisms underlying the protective effect of BH4 against ROS- and/or NO-induced endothelial cell injury will be discussed.

Keywords

• nitric oxide synthase
• nitric oxide
• hydrogen peroxide
• tetrahydrobiopterin
• endothelial cells
• cell injury