Lipid hydroperoxides as a source of singlet molecular oxygen

Abstract

Lipid hydroperoxides (LOOH) are formed in biological system by enzymatic and non-enzymatic pathways. These hydroperoxides exerts multiple damaging effects on cellular macromolecules and are also important regulators of cellular processes. Several classes of hydroperoxides including fatty acid, phospholipid, cholesterol and cholesteryl ester hydroperoxides have been detected and characterized both in vitro and in vivo. Although cells are normally endowed with enzymatic defenses capable to reduce LOOH to less reactive hydroxides, LOOH may accumulate in several pathological conditions and attention has been focused on elucidating their pathophysiological role. In the last years we have demonstrated the generation of singlet molecular oxygen (O 2 1 Δ g or 1 O 2) in several reactions involving LOOH. The generation of 1 O 2 was directly evidenced by spectroscopic detection and characterization of its light emission at 1,270 nm. Moreover, using 18-oxygen labeled hydroperoxides (L 18 O 18 OH) we could detect the formation of 18 O-labeled 1 O 2 by chemical trapping with anthracene derivatives followed by detection of the corresponding labeled endoperoxides by HPLC coupled to tandem mass spectrometry. The experimental evidences indicate that 1 O 2 is generated at a yield close to 10% by the Russell mechanism from LOOH, either free or in membranes, in the presence of biologically relevant oxidants, such as metal ions, peroxynitrite, HOCl and cytochrome c.