Cigarette smoke extract inhibits plasma paraoxonase activity by modification of the enzyme's free thiols

Cigarette smoking is associated with an increased incidence of premature atherosclerosis. Minimal information is available at the molecular level concerning the mechanism of action of cigarette smoke. Recent work has shown that paraoxonase (PON) protects low density lipoprotein against oxidation by Cu2+. The goal of the present study was to investigate the effect of cigarette smoke extract (CSE) on human plasma paraoxonase activity. The activity of paraoxonase was inhibited by the CSE in a dose- and time-dependent manner. The inhibition of PON activity by the CSE was reversed by the addition of glutathione or N-acetyl cysteine. Furthermore, we tested to see whether sulfhydryl compounds prevented the inhibition of PON activity caused by CSE. Sulfhydryl compounds prevented the inhibition of PON activity caused by CSE. But any amino compounds, such as N-acetyl lysine, N-acetyl arginine and aminoguanidine, failed to protect PON activity, indicating a specificity with regard to the ability of free thiols to buffer the deleterious components of CSE which inhibited PON activity. The observed inhibition of PON activity by CSE may account for the increased incidence of cardiovascular disease known to be present in smokers through the oxidative process of low density lipoprotein and its subsequent uptake by macrophage.