Expression of liver peroxisomal proteins as compared to other organelle marker enzymes in rats treated with hypolipidemic agents.
Peroxisome proliferation induced by 2 hypolipidemic agents (clofibrate and ciprofibrate) was studied in rats by complementary approaches, ie cell fractionation, electron microscopy, marker enzyme activities, immunoblotting and nucleic acid hybridization techniques. Administration of clofibrates for 2 and 52 weeks in doses of 500 ppm and 50 ppm respectively, or ciprofibrate for 2,28 and 52 weeks in doses of 250, 25 and 25 ppm respectively, did not alter the behavior of the peroxisomes after induction as shown by ultracentrifugation profiles. The peroxisome mass was increased as shown by the purification procedure. Specific enzymes (catalase and mostly cyanide insensitive palmitoyl CoA oxidase) were induced. A mechanism of peroxisome biogenesis might have been initiated ie cytosolic factor, ligand-receptor interaction and/or post-translational modification of the import. Increase in marker enzyme activities showed that the peroxisomes are the most responsive organelles in comparison to lysosomes, mitochondria and smooth endoplasmic reticulum (except for cytochrome P-450 LA omega-hydroxylase). Peroxisomal integral membrane proteins appeared to be differently induced: some of them were virtually absent in untreated rat liver but were strongly expressed in treated liver. Induction was sustained for 52 weeks, indicating that there was no compensatory mechanism.
Cherkaoui Malki
M
M
Laboratoire de Biochimie et Biologie Moléculaire (URA CNRS 531) Université de Franche-Comté, Besançon.
Bardot
O
O
Lhuguenot
J C
JC
Latruffe
N
N
D000818:Animals; D001483:Base Sequence; D002458:Cell Fractionation; D002994:Clofibrate / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015342:DNA Probes; D058607:Fibric Acids; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D015388:Organelles / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D015342:DNA Probes; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D002995:Clofibric Acid; C019304:ciprofibrate; D002994:Clofibrate