An in vitro demonstration of peroxisome proliferation and increase in peroxisomal beta-oxidation system mRNAs in cultured rat hepatocytes treated with ciprofibrate.
Using the normal adult rat hepatocytes, plated on rat tail collagen-coated dishes and fed a chemically defined medium, we demonstrate here that ciprofibrate at 0.1 mM concentration, increases significantly the mRNA levels of fatty acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein, and thiolase (the three enzymes of the beta-oxidation system), and causes peroxisome proliferation. Increase in mRNA levels of these genes was evident within 1 h and was maximal 24 h after the addition of ciprofibrate. In hepatocytes with the basal levels of these enzymes were low and further declined with time. Concomitant treatment of hepatocytes with cycloheximide did not inhibit or superinduce the mRNA levels, indicating that this induction may represent a primary (direct) effect of this compound on the expression of these genes and does not apparently involve short-lived repressor protein(s).
Thangada
S
S
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
Alvares
K
K
Mangino
M
M
Usman
M I
MI
Rao
M S
MS
Reddy
J K
JK
D000818:Animals; D015152:Blotting, Northern; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D058607:Fibric Acids; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D011506:Proteins; D012333:RNA, Messenger; D002995:Clofibric Acid; D003513:Cycloheximide; D002374:Catalase; C019304:ciprofibrate; D002994:Clofibrate