title: Degradation of HMG-CoA reductase in rat liver is cholesterol and ubiquitin independent.
abstract: In contrast with the accelerated degradation observed in tumor cells in response to sterols, hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase turnover in whole animals was not increased by dietary cholesterol. Furthermore, treating rats with lovastatin to lower hepatic cholesterol levels did not decrease the rate of degradation. The half-life remained in the 6 h range. Co-immunoprecipitation studies revealed that the amount of ubiquitin associated with the reductase was entirely dependent upon the amount of microsomal protein subjected to immunoprecipitation. The results indicate that in liver, neither the rate of reductase protein degradation nor the ubiquitin-proteasome system appear to play roles in mediating changes in HMG-CoA reductase protein levels in response to dietary cholesterol.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, United States. gness@hsc.usf.edu
authors.forename: Gene C
authors.initials: GC
authors.lastname: Ness
authors.forename: Reed C
authors.initials: RC
authors.lastname: Holland
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000821:Animal Feed; D000818:Animals; D002784:Cholesterol / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D025801:Ubiquitin; C067713:lactacystin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine