Expression of peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase enzyme and its mRNA in peroxisome proliferator-induced liver tumors.
We have examined ciprofibrate and dehydroepiandrosterone (DHEA)-induced hepatic lesions for the peroxisomal beta-oxidation system enzyme peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) and its mRNA using SDS-polyacrylamide gel electrophoresis, antibodies and cDNA probe. All 12 neoplastic nodules and nine hepatocellular carcinomas (HCCs) that were analyzed for PBE mRNA by in situ hybridization showed an intense signal comparable to the adjacent non-neoplastic liver. SDS-polyacrylamide gel electrophoresis of postnuclear fractions of six HCC and adjacent liver tissue showed a marked increase in an 80 kDa polypeptide. Immunoblot and Northern blot analysis showed a marked increase in PBE enzyme and PBE mRNA respectively in HCC and adjacent non-neoplastic liver tissue. In control livers (animals not treated with peroxisome proliferators), the levels of PBE enzyme and mRNA were very low or undetectable. The results of this study clearly indicate that peroxisome proliferator (PP)-induced liver lesions express peroxisomal enzymes to the same extent as adjacent liver and that these enzymes are not useful markers for identification of PP-induced lesions.
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
M S
MS
Rao
H
H
Ide
A V
AV
Yeldandi
S
S
Kumar
J K
JK
Reddy
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000032:analysis* / Q000235:genetics; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D003687:Dehydroepiandrosterone / Q000633:toxicity*; D004746:Enoyl-CoA Hydratase / Q000032:analysis* / Q000235:genetics; D058607:Fibric Acids; D007535:Isomerases / Q000032:analysis* / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000032:analysis* / Q000235:genetics; D063994:Peroxisomal Bifunctional Enzyme; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344
D058607:Fibric Acids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D002995:Clofibric Acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases; C019304:ciprofibrate