Rates of sterol synthesis from acetate and the levels of 3-hydroxy-3-methylglutaryl-CoA reductase activity (HMGCoA reductase, EC 1.1.1.3.4) in liver cell cultures and in L cells were strongly inhibited by highly purified preparations of 7a-hydroxycholesterol, 7/3-hydroxycholesterol, and ‘I-ketocholesterol. These steroids specifically diminished the activity of 3-hydroxy-3-methylglutaryl-CoA red...

The activity of acetoacetyl-CoA (AcAc-CoA) ligase (E.C.6.2.1.16) in hepatocytes from rats was shown to be the same as the activity in homogenates of their livers. In hepatocytes treated with 25-hydroxycholesterol, AcAc-CoA ligase, 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and rates of sterol synthesis were substantially decreased. Hepatocytes treated with high density lipoprotein (HDL...

In insects, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) synthesizes mevalonate for the production of nonsterol isoprenoids, which are essential for growth and differentiation. To understand the regulation and developmental role of HMG-CoA reductase, we have cloned a full-length HMG-CoA reductase cDNA from the cockroach Blattella germanica. This cDNA clone was isolated using as a p...

In this paper, we assess the relative degree of regulation of the rate-limiting enzyme of isoprenoid biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, by sterol and nonsterol products of mevalonate by utilizing cultured Chinese hamster ovary cells blocked in sterol synthesis. We also examine the two other enzymes of mevalonate biosynthesis, acetoacetyl-CoA thiolase and HM...

Healthy endothelium is essential for undisturbed functioning of the cardiovascular system, while endothelial dysfunction leads to its various pathologies. For example endothelial dysfunction precedes clinical symptoms of atherothrombosis, such as acute coronary syndrome, ischemic stroke, peripheral arterial disease or diabetic microangiopathies e.g. retinopathy and nephropathy. Accordingly, pha...

Renal proximal tubule cells are responsible for the reabsorption of proteins that are present in the tubular lumen. This occurs by receptor-mediated endocytosis, a process that has a requirement for some GTP-binding proteins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase used for the therapeutic reduction of cholesterol-containing plasma lipoproteins. However, the...

A patient developed direct renal tubular toxicity on high-dose HMG-CoA reductase inhibitor (statin) therapy. Considerable renal damage was present by the time the injury became apparent. Urine abnormalities regressed after stopping the drug and reappeared after about 2 weeks following re-challenge. Although tubular damage may be slight and relatively difficult to detect, it is possible that cum...

Background and Purpose—Statins reduce the risk of stroke recurrence, but the benefits of statins in improving outcome of acute stroke patients have not been well explored. Methods—We assessed potential effects of statins initiated before or within 4 weeks of stroke on 90-day outcome. Favorable outcomes were National Institutes of Health Stroke Scale (NIHSS) score 2 at 12 weeks and modified Rank...