Inhibition of lecithin: cholesterol acyltransferase activity in human blood plasma by cigarette smoke extract and reactive aldehydes.
Cigarette smoking is a risk factor for atherosclerosis. It is conceivable that reactive chemical components in cigarette smoke may adversely affect reverse cholesterol transport at the level of lecithin: cholesterol acyltransferase (LCAT) and promote atherogenesis. Hence, the effect of cigarette smoke extract (CSE) on the activity of LCAT in human plasma was studied. When incubated with plasma, CSE caused both concentration- and time-dependent losses of LCAT activity. Addition of glutathione, but not ascorbate, to plasma prevented loss of LCAT activity caused by CSE. Incubation of plasma with some reactive aldehydes known to be present in cigarette smoke also inhibited LCAT activity. Among five aldehydes tested, acrolein was the strongest inhibitor of LCAT, with complete enzyme inhibition occurring at 1 mM. Acetaldehyde was the weakest inhibitor of LCAT, with 85% enzyme inhibition at 50 mM. Hexanal, formaldehyde, and malondialdehyde completely inhibited LCAT activity at 10, 50, and 50 mM, respectively. When plasma was incubated with 1 mM acrolein in the presence of 2.5 mM glutathione or dihydrolipoic acid, 100 and 57% of LCAT activity, respectively, remained after incubation. This finding suggest that reactive aldehydes may form adducts with certain free sulfhydryl groups functioning in the active site of LCAT to inhibit enzyme activity. It is concluded that reactive aldehydes are at least partially responsible for the reduction in LCAT activity in plasma treated with CSE.
D000328:Adult; D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000209:etiology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000097:blood; D010947:Plants, Toxic; D012906:Smoke; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014026:Nicotiana
D000447:Aldehydes; D012906:Smoke; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D005978:Glutathione