The effect of nitric oxide on the lysosomal oxidation of low-density lipoprotein

Abstract

Oxidation of low density lipoprotein (LDL) in lysosome might play a key role in the development of atherosclerosis. Nitric oxide donors have been shown to inhibit iron or copper induced LDL oxidation. Through the use of spectrophotometry, HPLC and in THP-1 cell culture, we investigated the effect of nitric oxide on LDL oxidation at pH 4.5. Our findings indicate that NO released from S-nitroso-n-acetyl penicillamine (SNAP) (10μM) was able to inhibit the oxidation of LDL. Moreover, nitric oxide produced from SNAP was able to scavenger the lipid radicals thus, little ceroid resulting from lysosomal LDL oxidation was detected in human macrophages. This finding suggests that the antioxidant SNAP could be a potential tool to assess the LDL oxidation hypothesis and could be a novel therapeutic approach to treat atherosclerosis. However, nitric oxide might be pro-oxidant in human macrophages as shown by the results with the iNOS inhibitor 1400W