Polychlorinated biphenyls interfere with the regulation of hydroxymethylglutaryl-coenzyme A reductase activity in rat liver via enzyme-lipid interaction and at the transcriptional level.
Feeding a 0.05% polychlorinated biphenyl-supplemented diet to rats resulted in an increase of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase activity within 9 days, followed by a decrease towards normal levels. Polychlorinated biphenyls were incorporated into the microsomal membrane. There was a concomitant decrease in the cholesterol/phospholipid ratio in the microsomal fraction. Immunotitration studies strongly suggested that polychlorinated biphenyls modulate preexisting 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by changing the lipid environment of the enzyme. 32P-labeled cDNA probes were used to study the levels of mRNA coding for 3-hydroxy-3-methylglutaryl coenzyme A reductase during polychlorinated biphenyl feeding. Northern dot hybridization experiments showed an increase in the amount of this mRNA. This stimulation correlated with the increase in the activity of the enzyme but was more pronounced. The data suggest that polychlorinated biphenyls act on the regulation of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity by enzyme-lipid interaction and at the transcriptional level.
D000284:Administration, Oral; D000818:Animals; D002784:Cholesterol / Q000032:analysis; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D008862:Microsomes, Liver / Q000032:analysis / Q000187:drug effects / Q000201:enzymology*; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects
D008055:Lipids; D012333:RNA, Messenger; D002784:Cholesterol; D011078:Polychlorinated Biphenyls; D006903:Hydroxymethylglutaryl CoA Reductases