Nitrone spin trap lipophilicity as a determinant for inhibition of low density lipoprotein oxidation and activation of interleukin-1 beta release from human monocytes.

摘要: One means by which oxidation of low density lipoproteins (LDL) may contribute to atherogenesis is their ability induce the release interleukin-1 beta from monocytes. In present study, effect lipophilic nitrone spin trap alpha-phenyl-tert-butylnitrone (PBN) on lipoprotein and subsequent was examined. The hydrophilic alpha-(4-pyridyl 1-oxide)-N-tert butylnitrone (POBN) also studied evaluate importance localization within lipoprotein. PBN inhibited copper-induced modification in a dose-dependent fashion as judged measurement thiobarbituric acid reactive substances, electrophoretic mobility, fluorescence changes, while POBN relatively ineffective. As demonstrated electron resonance spectrometry, spectra adducts were highly immobilized, reflects presence LDL matrix. Experiments using chromium oxalate, paramagnetic relaxing agent, revealed that adduct composed mobile component (exposed aqueous phase) an immobilized component, localized lipid-protein interface or bulk lipid. Cholesteryl ester phospholipid dispersions only core cholesteryl esters are subject used compare POBN. Again, prevented lipids had little effect, further suggesting capable LDL. agreement, attenuation decreased human Conversely, cells incubated with copper-oxidized lipoproteins. These results suggest prevent its biologic effect(s) requires incorporation into particle.