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Journal of Lipid Research, Vol 36, 1474-1482, Copyright © 1995 by Lipid Research, Inc.
KR Feingold, AS Pollock, AH Moser, JK Shigenaga and C Grunfeld
Recent studies have shown that the administration of endotoxin (LPS) and
cytokines to Syrian hamsters increases serum cholesterol levels, hepatic
cholesterol synthesis, and the activity, protein levels, and mRNA levels of
hepatic HMG-CoA reductase. Despite the greater than 10- fold increase in
HMG-CoA reductase mRNA levels, LPS had only minimal effects on hepatic LDL
receptor mRNA levels. In the present study, we demonstrate that LPS
increases the transcription rate in the liver of HMG-CoA reductase mRNA
approximately 4- to 5-fold without affecting LDL receptor mRNA
transcription. Most stimuli that regulate HMG-CoA reductase and LDL
receptor mRNA levels also regulate, in parallel, HMG- CoA synthase and
farnesyl pyrophosphate (FPP) synthetase. However, in chow-fed animals, LPS
and cytokines (TNF, IL-1, TNF + IL-1) increased hepatic HMG-CoA reductase
mRNA levels without increasing LDL receptor, HMG-CoA synthase, or FPP
synthetase mRNA levels. The feeding of cholesterol or bile resin binders
regulates the mRNA levels of HMG-CoA reductase, LDL receptor, HMG-CoA
synthase, and FPP synthetase. In both cholesterol- and colestipol-fed
animals, LPS increased HMG-CoA reductase mRNA levels while either
decreasing or causing minimal increases in the mRNA levels of the other
proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Discordant regulation of proteins of cholesterol metabolism during the acute phase response
Department of Medicine, University of California, San Francisco, USA.
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