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Polychlorinated biphenyls interfere with the regulation of hydroxymethylglutaryl-coenzyme A reductase activity in rat liver via enzyme-lipid interaction and at the transcriptional level.
Biochim. Biophys. Acta 837, 85-93 (1985)
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-methylglutaryl coenzyme A reductase activity by enzyme-lipid interaction and at the transcriptional level.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0006-3002
Journal Biochimica et Biophysica Acta
Quellenangaben Volume: 837, Issue: 1, Pages: 85-93
Institute(s) Institut für Toxikologie und Biochemie