Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.

Patrick, T. S.; Gil, Gregorio; Südhof, Thomas C.; Bilheimer, David W.; Goldstein, Joseph L.; Brown, Michael S.

doi:10.1073/pnas.83.21.8370

Cited by 292 publications

(134 citation statements)

References 28 publications

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“…Oxysterols stimulate expression of CYP7A1, thereby increasing conversion of cholesterol to bile acids (Lehmann et al, 1997) Observed decrease in HMG Co A reductase activity in HFD+FECG rats, indicates diminished de novo cholesterol synthesis. Decreased hepatic cholesterol levels are known to induce LDL receptor expression to promote LDL clearance from circulation in order to maintain hepatic cholesterol homeostasis (Ma et al, 1986). Thus it can be speculated that FECG decreases circulating LDL via increased LDL-R expression.…”

Section: Discussionmentioning

confidence: 99%

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

Jadeja¹,

Thounaojam²,

Ansarullah³

et al. 2010

Rev. bras. farmacogn.

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RESUMO: "Clerodendron glandulosum Coleb., Verbenaceae, melhora a dieta rica em gordura induzida por alteração no metabolismo de lipídios e colesterol em ratos." Este estudo foi realizado para avaliar a eficácia do extrato liofilizado das folhas de Clerodendron glandulosum Coleb., Verbenaceae (FECG), em alterar o metabolismo de lipídios e colesterol em ratos hiperlipidêmicos alimentados em uma dieta rica em gordura. Plasma e perfil lipídico hepático, lipídeos e enzimas que metabolizam o colesterol em tecidos-alvo e o conteúdo de lipídeos fecais totais e ácidos biliares foram avaliados em ratos normolipidêmicos e hiperlipidêmicos tratados com FECG. Os resultados foram comparados com a droga sintética hipolipemiante Lovastatina (LVS). Os resultados indicam que FECG foi capaz de regular positivamente a hiperlipidemia induzida experimentalmente por alteração significativa no perfil lipídico do plasma e tecidos. Estes resultados podem ser atribuídos à absorção reduzida, a eliminação efetiva e catabolismo aumentado de lipídeos e colesterol, possivelmente devido ao alto teor de saponina e fitoesteróis em C. glandulosum Coleb. Uso de extrato de C. glandulosum como um possível agente terapêutico contra a hipercolesterolemia e hipertrigliceridemia é indicado. Unitermos:Clerodendron glandulosum, Verbenaceae, hiperlipidemia, hipercolesterolemia. ABSTRACT:The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG) on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS). Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

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Section: Discussionmentioning

confidence: 99%

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

Jadeja¹,

Thounaojam²,

Ansarullah³

et al. 2010

Rev. bras. farmacogn.

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“…This molecule is absorbed and taken to the liver where it has an inhibitory effect on the enzyme HMG-CoA reductase, thus reducing de n o w cholesterol synthesis. According to reports of the effects of proprietary HMG-CoA reductase inhibitors, reducing cholesterol synthesis results in a compensatory increase in LDL-receptor activity and, hence, a reduction in plasma cholesterol (Ma et al 1986).…”

Section: E F F E C T S O N L I P O P R O T E I N M E T a B O L I S Mmentioning

confidence: 99%

The Influence of Legume Seeds on Human Plasma Lipid Concentrations

Kingman

1991

Nutr. Res. Rev.

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“…As a result of the reduction of cellular sterol pools, there is compensatory upregulation of cell-surface receptors for cholesterol-containing low density lipoproteins (LDL), an effect which takes place mainly in the liver (2)(3)(4). This mechanism underlies the therapeutic use of the statins to lower plasma cholesterol and particularly the levels of LDL.…”

mentioning

confidence: 99%

Inhibitors of HMG-CoA Reductase Reduce Receptor-mediated Endocytosis in Human Kidney Proximal Tubular Cells

Verhulst¹,

D’Haese²,

Broe³

2004

Journal of the American Society of Nephrology

123

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Abstract. The proximal tubular cells of the kidney are responsible for reabsorption of proteins from the tubular lumen. In a study using Opossum kidney (OK) cells, receptor-mediated protein endocytosis was reduced by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which are widely used for therapeutic reduction of plasma cholesterol levels. To explore the possible clinical relevance of the observations in OK cells, protein endocytosis in human kidney tubular cells was investigated in the presence and absence of statins.The uptake of FITC-labeled albumin in these cultures of human kidney tubular cells was investigated by microscopy, flow cytometry and spectrofluorometry. Protein uptake occurred selectively into proximal tubular cells while it was absent in distal tubular/collecting duct cells. Three statins (simvastatin, pravastatin, and rosuvastatin) significantly inhibited the uptake of protein in a concentration-dependent way. This inhibitory effect of statins could be prevented by the co-addition of mevalonate, the product of HMG-CoA reductase. This effect was not the result of a statin-induced cytotoxicity since cell-viability was unaffected. Finally, it was demonstrated that statins strongly inhibited cholesterol synthesis in the human kidney tubular cells.These data suggest that statins have the potential to inhibit albumin uptake by the human proximal nephron as a result of inhibition of HMG-CoA reductase in the proximal tubule cells. Taken into account the data of the accompanying manuscript this inhibitory effect most probably results from a reduced prenylation of some proteins critically involved in endocytosis. It is suggested that these data help to explain the occurrence of proteinuria in some patients treated with high statin doses.Statins, by their ability to inhibit 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, the rate-limiting enzyme of the sterol pathway, are potent inhibitors of sterol biosynthesis (1). As a result of the reduction of cellular sterol pools, there is compensatory upregulation of cell-surface receptors for cholesterol-containing low density lipoproteins (LDL), an effect which takes place mainly in the liver (2-4). This mechanism underlies the therapeutic use of the statins to lower plasma cholesterol and particularly the levels of LDL. However, many additional effects of statins on cell function have been described in the literature (5). These appear to be independent of cellular cholesterol homeostasis and are collectively termed "pleiotropic effects". Many of these have been shown to result from the depletion of mevalonate (the HMG-CoA conversion product)-derived intermediates of the sterol pathway, particularly the isoprenoid pyrophosphates such as geranylgeranyl pyrophosphate (GGPP). Isoprenoid pyrophosphates are required by the cells for the post-translational modification of a range of proteins, especially GTP-binding proteins. In the accompanying publication (6), it has been shown that receptormediated endocytosis by opossum kidney (OK) c...

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Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.

Cited by 292 publications

References 28 publications

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

The Influence of Legume Seeds on Human Plasma Lipid Concentrations

Inhibitors of HMG-CoA Reductase Reduce Receptor-mediated Endocytosis in Human Kidney Proximal Tubular Cells

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