Ethanol inhibits asialoglycoprotein receptor synthesis but augments its mRNA expression in a human hepatoma cell line.
The effect of ethanol on the expression of asialoglycoprotein receptor protein and its mRNA was studied in a human hepatoma cell line, HepG2. The number of asialoglycoprotein receptors on the cell surface was decreased to 60% of the control level, without a loss in affinity, by incubating the cells with 100 mM ethanol. The decrease in cell surface asialoglycoprotein receptors was paralleled by a decrease in total receptor numbers, including intracellular and surface receptors. The internalization of asialoglycoprotein was also diminished, to 44% of that in control cells. The decreases in cell surface receptors and total receptor numbers were partially restored by 2 mM 4-methylpyrazole, suggesting that ethanol metabolites participated in the diminution of asialoglycoprotein receptor expression. However, the steady-state expression of asialoglycoprotein receptor mRNA was increased in ethanol-treated cells and further augmented by a longer ethanol exposure. These paradoxical results, i.e., the decrease of asialoglycoprotein receptor protein and the increase of its mRNA expression, suggest that the reduction in the asialoglycoprotein receptor protein is a post-transcriptional event and that a possible feedback regulatory mechanism may control asialoglycoprotein receptor gene transcription and/or impair the degradation of its mRNA.
Kohgo
Y
Y
Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Mogi
Y
Y
Kato
J
J
Nakaya
R
R
Nakajima
M
M
Katsuki
S
S
Niitsu
Y
Y
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D000431:Ethanol / Q000494:pharmacology*; D000077604:Fomepizole; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D014407:Tumor Cells, Cultured
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D015345:Oligonucleotide Probes; D011720:Pyrazoles; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000431:Ethanol; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase