The acylation of proteins by xenobiotic amphipathic carboxylic acids in cultured rat hepatocytes.
Three xenobiotic amphipathic carboxylates, namely MEDICA 16, nafenopin and bezafibrate, which differ remarkably in their hydrophobic backbones, were found to acylate membrane and cytosolic liver proteins in cultured rat hepatocytes. The acylation patterns observed were time- and dose-dependent, and the acylated residue consisted of the original xenobiotic. The acylation patterns generated by the three xenobiotic carboxylates included common proteins which were acylated by the three xenobiotics (e.g. proteins of 32, 52, 56 and 72 kDa) as well as unique proteins which were specifically acylated by the respective xenobiotics. The acylation of liver proteins by either MEDICA 16 or nafenopin remained unaffected under conditions where protein synthesis was completely inhibited by cycloheximide. Protein acylation thus offers a common mode of action of xenobiotic amphipathic carboxylates, which may, however, result in diverse xenobiotyl-protein adducts. The xenobiotyl-acylated proteins might be involved in triggering some of the biological effects exerted by xenobiotic amphipathic carboxylates employed as hypolipidaemic effectors, peroxisomal proliferators or preadipocyte convertors.
Hertz
R
R
Department of Biochemistry, Hewbrew University-Hadassah Medical School, Jerusalem, Israel.
Bar-Tana
J
J
D000215:Acylation; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D019814:Myristic Acid; D009227:Myristic Acids / Q000494:pharmacology; D009255:Nafenopin / Q000494:pharmacology*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D009227:Myristic Acids; D010169:Palmitic Acids; D011422:Propionates; D011506:Proteins; D009255:Nafenopin; D019814:Myristic Acid; D019308:Palmitic Acid; C056166:MEDICA 16; D003513:Cycloheximide; D001629:Bezafibrate