Effect of ethanol on lipoprotein secretion in two human hepatoma cell lines, HepG2 and Hep3B.
The two human hepatoma cell lines, HepG2 and Hep3B, have been demonstrated to metabolize ethanol efficiently even in the absence of alcohol dehydrogenase. By using specific metabolic inhibitors, it was found that the microsomal ethanol-oxidizing system (MEOS) plays a significant role in ethanol metabolism in these two cell lines. There is a strong positive correlation between the rates of ethanol metabolism and the total cytochrome P-450 levels in the hepatoma cells. The involvement of the cytochrome P-450 system was further supported by the induction of aniline p-hydroxylase activity after ethanol treatment. However, the 3- to 4-fold elevation in aniline p-hydroxylase activity was not accompanied by an increase in cytochrome P450IIE1 mRNA level. Exposure of HepG2 and Hep3B cells to ethanol resulted in an increase of accumulation of apoA-I (15%-45% over control) in a dose-dependent manner (from 5 to 50 mM) of ethanol over a 24-hr period. All other major apolipoproteins which included apo CII, apo CIII and apoE, with the exception of apoB, were not affected by these treatments. At a concentration of ethanol of 25 mM or greater, accumulation of apoB, VLDL and LDL triglyceride were increased by 20% to 25% over the control level. Elevation of HDL cholesterol (40%-70% over control) was observed when the cells were exposed to an ethanol concentration of > or = 10 mM. Metyrapone, which inhibited the MEOS, was capable of blocking the induction of apoAI caused by ethanol treatment.
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Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
D000429:Alcohol Oxidoreductases / Q000502:physiology; D000815:Aniline Hydroxylase / Q000502:physiology; D016632:Apolipoprotein A-I / Q000378:metabolism; D001053:Apolipoproteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008113:Liver Neoplasms; D008657:Metabolic Clearance Rate / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C092153:microsomal ethanol-oxidizing system; D000815:Aniline Hydroxylase