Ethanol increases apolipoprotein B mRNA editing in rat primary hepatocytes and McArdle cells.
Apolipoprotein B (apoB) mRNA editing involves a site-specific cytidine to uridine transition catalyzed by the cytidine deaminase, APOBEC-1, in the context of and regulated by a multi-protein-containing editosome. ApoB mRNA editing in vivo is subject to tissue specific, developmental and metabolic regulation. We demonstrate for the first time that the amount of edited apoB mRNA in rat primary hepatocytes is markedly increased subsequent to transient treatment with ethanol in vitro. The apparent change in editing efficiency was dose-dependent (from 0.1%-2.4% initial ethanol dose) and occurred with rapid onset. The proportion of edited apoB mRNA was also markedly enhanced in a rat hepatoma cell line, McArdle RH7777 cells and in a stable McArdle cell line over-expressing APOBEC-1 by transient treatment with 2.5 % ethanol. In contrast, the apoB mRNA editing in a human hepatoma cell line, HepG2 cells and a stable HepG2 cell line over-expressing APOBEC-1 did not respond to ethanol treatment. The data support the possibility that editing activity is ethanol-responsive but suggest that this change is cell type-specific.
Van Mater
D
D
Departments of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642, USA.
Sowden
M P
MP
Cianci
J
J
Sparks
J D
JD
Sparks
C E
CE
Ballatori
N
N
Smith
H C
HC
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D017393:RNA Editing / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D001055:Apolipoproteins B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D000431:Ethanol