Ethanol stimulates apolipoprotein A-I secretion by human hepatocytes: implications for a mechanism for atherosclerosis protection.
Ethanol intake in humans has been shown to have a protective effect against coronary heart disease. The specific mechanism by which ethanol is cardioprotective has not been elucidated. Apolipoprotein (apo) A-I, the major protein of high-density lipoprotein (HDL), takes up cellular cholesterol, thus initiating reverse cholesterol transport whereby excess tissue cholesterol is eliminated. Using highly specific antibodies, we have found that ethanol increases apo A-I secretion and the incorporation of radiolabeled leucine into apo A-I by human hepatocytes (Hep-G2 cells). In addition, we have found that apo A-I molecules induced by ethanol have the ability to efflux cholesterol from human fibroblasts in vitro, and that apo A-I mass directly correlates with cholesterol efflux levels. At 10, 20, and 100 mmol/L, ethanol stimulated apo A-I secretion by 130%, 136%, and 162% of control, respectively (control, 3.71 micrograms apo A-I/micrograms DNA), also stimulating the incorporation of 3H-leucine into newly synthesized apo A-I by 115%, 131%, and 159% of control (control, 111 cpm/micrograms DNA/h). The ethanol-induced apo A-I from Hep-G2 cells (incubated with 0, 10, 20, and 100 mmol/L ethanol) effluxed 2%, 14%, 16%, and 32% label (per h/mL incubation medium), respectively. Apo A-I mass correlated linearly with cholesterol efflux (r = .99, P less than .01). This data indicates that the cardioprotective role of moderate ethanol intake in humans is mediated by its stimulatory action on hepatic apo A-I secretion, thus defining the physiological basis for increased plasma apo A-I levels in vivo.
Amarasuriya
R N
RN
Cholesterol Center, School of Medicine, University of California, Irvine 90822.
Gupta
A K
AK
Civen
M
M
Horng
Y C
YC
Maeda
T
T
Kashyap
M L
ML
D016632:Apolipoprotein A-I / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism / Q000517:prevention & control*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007120:Immunochemistry; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism
D016632:Apolipoprotein A-I; D012709:Serum Albumin; D000431:Ethanol; D002784:Cholesterol; D007930:Leucine