Results from large-scale clinical trials of lipid lowering with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have led to a revolution in the management of atherosclerosis. In addition to their potent effect on serum lipid levels, statins influence several other cellular pathways, including those involving inflammatory, oxidative, and thrombotic processes. These...

OBJECTIVE A recent study identified a new class of compounds designated as the sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) ligands that putatively bind to SCAP, leading to increased LDL receptor (LDLR) expression. In this study, we examined the effects of SCAP ligand GW707 in comparison with lovastatin and cytokine oncostatin M (OM) on the regulation of ...

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the ileum of rats was inactivated by Mg2+-ATP and reversibly reactivated by cytoplasmic activator from the liver. The mevalonate kinase reaction was presumably not involved in this inactivation. Studies of nucleotide specificity for the inactivation revealed that ATP was most effective in the reaction among the nucleotides tested. In ...

We have suggested previously, measuring 14C-acetate incorporation into free cholesterol, that oral administration of policosanol inhibits hepatic cholesterol biosynthesis in rats. Nevertheless, since acetate has limitations to study cholesterol synthesis in vivo, we now investigate rates of incorporation of labeled water into hepatic sterol after policosanol treatment. Absolute rates of incorpo...

By taking advantage of the crystallographic data of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) complexed with statins, a quantum biochemistry study based on the density functional theory is performed to estimate the interaction energy for each statin when one considers binding pockets of different sizes. Assuming a correlation between statin potency and the strength of the total HMG...

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on coronary events have generally been attributed to their hypocholesterolaemic properties. However, as mevalonate and other intermediates of cholesterol synthesis (isoprenoids) are necessary for cell proliferation and other important cell functions, effects other than cholesterol reduction ...

A heat-stable protein inhibitor of the hydroxymethylglutaryl-CoA reductase phosphatase 2A activity has been identified and purified to homogeneity, as judged by polyacrylamide gel electrophoresis. The apparent molecular mass was 20,000 Da. The protein lost its inhibitory properties when incubated with trypsin or treated with ethanol. The inhibitor protein does not inhibit type 1 phosphatase whe...

In addition to lowering low-density lipoprotein cholesterol, statins improve vascular function by cholesterol-independent effects in experimental models. These extrahepatic effects are often called “pleiotropic”; however, specific underlying molecular mechanisms have been identified in animal and cell culture studies. They relate to the inhibition of isoprenylation of small G proteins. Inhibiti...

Statin inhibitors, used to control hypercholesterolemia, trigger apoptosis of hematologic tumor cells and therefore have immediate potential as anticancer agents. Evaluations of statins in acute myelogenous leukemia and multiple myeloma have shown that statin efficacy is mixed, with only a subset of tumor cells being highly responsive. Our goal was to distinguish molecular features of statin-se...