UNLABELLED The effects of lovastatin therapy on the parameters of body cholesterol metabolism were explored in nine hypercholesterolemic patients. Long-term cholesterol turnover studies were performed before therapy, and were repeated after 15 mo of lovastatin therapy (40 mg/d) while continuing on therapy. The major question addressed was whether a reduction in plasma cholesterol level with lov...

Dichloroacetate (DCA) markedly reduces circulating cholesterol levels in animals and in patients with combined hyperlipoproteinemia or homozygous familial hypercholesterolemia (FH). To investigate the mechanism of its cholesterol-lowering action, we studied the effects of DCA and its hepatic metabolites, glyoxylate and oxalate, on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase ...

The effects of tunicamycin on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and cholesterol biosynthesis have been studied in cultured C-6 glial cells. Depending on culture conditions, exposure to tunicamycin caused either a marked inhibition of induction of HMG-CoA reductase activity or, under steady state conditions, a marked reduction in enzymatic activity. Incorporation...

coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons. Am J Cardiol 2001;88:693–5. 12. Novaro GM, Tiong IY, Pearce GL, Lauer MS, Sprecher DL, Griffin BP. Effect of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of calcific aortic stenosis. Circulation 2001;104: 2205–9. 13. Bellamy MF, Pellikka PA, Klarich KW, Tajik ...

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...

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are a breakthrough in the treatment of high serum cholesterol. Several recent clinical trials demonstrate that statins can substantially reduce both morbidity and mortality from CHD. They are becoming a mainstay in management of patients with established CHD (secondary prevention), and they hold promise for high-risk patients witho...

Large-scale phenotypic screening presents challenges and opportunities not encountered in typical forward or reverse genetics projects. We describe a modular database and laboratory information management system that was implemented in support of the Chloroplast 2010 Project, an Arabidopsis (Arabidopsis thaliana) reverse genetics phenotypic screen of more than 5,000 mutants (http://bioinfo.bch....

1) In kinetic studies, mevinolin proved to be a highly specific inhibitor of partially purified yeast HMG-CoA reductase (Ki = 3.5 nM towards HMG-CoA) and of microsomal HMG-CoA reductase from etiolated radish seedlings (Ki = 2.2 nM). At low concentrations of NADPH, the inhibitor counteracts the sigmoidal response of plant HMG-CoA reductase activity towards the cosubstrate. At higher concentratio...