35] Using peroxynitrite as oxidant with low-density lipoprotein

Abstract

This chapter focuses on the product of the reaction between the radical's nitric oxide (NO . ) and superoxide (O 2 - ), peroxynitrite, by which it modify low-density lipoprotein (LDL). The development of atherosclerosis is associated with the oxidative modification of LDL, the major cholesterol transport protein in humans. The most likely mechanism involves reaction with preformed lipid hydroperoxides (LOOH), producing radicals in the lipid phase that decompose to produce reactive aldehydes that modify the protein. Peroxynitrite rapidly decays under physiological conditions through its protonated form, peroxynitrous acid (HOONO), with a half-life of less than 1 sec. The peroxynitrite anion (ONOO – ) is relatively stable particularly under basic conditions; however is itself a reactive species. The production of reactive free radicals by peroxynitrite is the route through which it can oxidize LDL, because it oxidizes the lipophilic antioxidant α-tocopherol directly, thereby reducing the antioxidant defenses of the lipoprotein. To oxidize LDL in vitro either preformed peroxynitrite (ONOO-) can be added directly, or produced in situ by the simultaneous generation of NO . and O 2 – .