scholarly journals Sphingolipids and cellular cholesterol homeostasis. Effect of ceramide on cholesterol trafficking and HMG CoA reductase activity

2008 ◽  
Vol 474 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Papasani V. Subbaiah ◽  
Jennifer M. Sowa ◽  
Dev K. Singh
Keyword(s):  
Reductase Activity ◽  
Cholesterol Homeostasis ◽  
Cholesterol Trafficking ◽  
Hmg Coa Reductase ◽  
Cellular Cholesterol ◽  
Coa Reductase

Regulation of hepatic cholesterol biosynthesis by berberine during hyperhomocysteinemia

2011 ◽  
Vol 300 (3) ◽  
pp. R635-R643 ◽  
Author(s):  
Nan Wu ◽  
Lindsei K. Sarna ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Lipid Accumulation ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Homeostasis ◽  
Enzyme Treatment ◽  
Hepatic Cholesterol ◽  
Hmg Coa Reductase ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Coa Reductase

Hyperhomocysteinemia, an elevation of blood homocysteine levels, is a metabolic disorder associated with dysfunction of multiple organs. We previously demonstrated that hyperhomocysteinemia stimulated hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase leading to hepatic lipid accumulation and liver injury. The liver plays an important role in cholesterol biosynthesis and overall homeostasis. HMG-CoA reductase catalyzes the rate-limiting step in cholesterol biosynthesis. Hepatic HMG-CoA reductase is a major target for lowering cholesterol levels in patients with hypercholesterolemia. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on hepatic cholesterol biosynthesis in hyperhomocysteinemic rats and to identify the underlying mechanism. Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 4 wk. HMG-CoA reductase activity was markedly elevated in the liver of hyperhomocysteinemic rats, which was accompanied by hepatic lipid accumulation. Activation of HMG-CoA reductase was caused by an increase in its gene expression and a reduction in its phophorylation (an inactive form of the enzyme). Treatment of hyperhomocysteinemic rats with berberine for 5 days inhibited HMG-CoA reductase activity and reduced hepatic cholesterol content. Such an inhibitory effect was mediated by increased phosphorylation of HMG-CoA reductase. Berberine treatment also improved liver function. These results suggest that berberine regulates hepatic cholesterol biosynthesis via increased phosphorylation of HMG-CoA reductase. Berberine may be therapeutically useful for the management of cholesterol homeostasis.

Cholesterol homeostasis in cultures of rat heart myocytes: relationship to cellular hypertrophy

1994 ◽  
Vol 267 (5) ◽  
pp. H1689-H1697 ◽  
Author(s):  
H. Shmeeda ◽  
D. Petkova ◽  
Y. Barenholz
Keyword(s):  
Rat Heart ◽  
Molecular Mechanisms ◽  
Reductase Activity ◽  
Feedback Regulation ◽  
Cholesterol Homeostasis ◽  
Neonatal Rat ◽  
Hmg Coa Reductase ◽  
Relative Contribution ◽  
Rat Heart Myocytes ◽  
Coa Reductase

The mechanism leading to accumulation of cholesterol in hypertrophic cultures of neonatal rat heart myocytes was investigated in light of its relevance to aging-related hypertrophy of myocardial tissue. Lipoprotein turnover was low in young cells (days 4–6) and further depressed in older cells (days 12–14), and therefore could not account for the increase in cholesterol levels. 3H2O incorporation into cell monolayers and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity in cell-free extracts demonstrated a substantial increase in cholesterogenesis during culture aging. Cholesteryl ester (CE) synthesis, cellular levels, and acyl-CoA:cholesterol O-acyltransferase (ACAT) activity decreased. The rate of CE hydrolysis did not change. Although cholesterol efflux from cells decreased 50%, its relative contribution to cholesterol accumulation was small. Our results indicate that accumulation of cholesterol in aging rat myocyte cultures is primarily due to changes in the endogenous metabolism of cholesterol and not due to a lipoprotein-mediated pathway. This implicates an impairment of the feedback regulation of HMG-CoA reductase and ACAT. These findings have important implications for understanding the molecular mechanisms underlying aging-related myocardial hypertrophy.

scholarly journals The absolute rate of cholesterol biosynthesis in monocyte-macrophages from normal and familial hypercholesterolaemic subjects

1984 ◽  
Vol 219 (2) ◽  
pp. 461-470 ◽  
Author(s):  
D D Patel ◽  
C R Pullinger ◽  
B L Knight
Keyword(s):  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Specific Radioactivity ◽  
Density Lipoprotein ◽  
Cellular Protein ◽  
True Rate ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
In Cells

The true rate of cholesterogenesis in cultured monocyte-macrophages was determined from the incorporation of [2-14C]acetate into cholesterol, using the desmosterol (cholesta-5,24-dien-3 beta-ol) that accumulated in the presence of the drug triparanol to estimate the specific radioactivity of the newly formed sterols. It was shown that this procedure could be successfully adapted for use with cultured monocytes despite the accumulation of other unidentified biosynthetic intermediates. In cells maintained in 20% (v/v) whole serum approx. 25% of the sterol carbon was derived from exogenous acetate. Cholesterol synthesis was as high in normal cells as in cells from homozygous familial hypercholesterolaemic (FH) subjects and accounted for 50% of the increase in cellular cholesterol. The addition of extra low-density lipoprotein (LDL) reduced cholesterol synthesis, apparently through a decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). When incubated in lipoprotein-deficient serum some cells did not survive, but those that remained showed a normal increase in protein content; the amount of cellular protein and cholesterol in each well did not increase and cholesterol synthesis was reduced by over 80%. HMG-CoA reductase activity fell less dramatically and the proportion of sterol carbon derived from exogenous acetate increased, suggesting that the low rate of cholesterogenesis with lipoprotein-deficient serum was due to a shortage of substrate. The results indicate that under normal conditions monocyte-macrophages obtain cholesterol from endogenous synthesis rather than through receptor-mediated uptake of LDL, and that synthesis together with non-saturable uptake of LDL provides the majority of the cholesterol required to support growth.

scholarly journals The roles of different protein kinases and of calmodulin in the effects of Ca2+ mobilization on 3-hydroxy-3-methylglutaryl-CoA reductase activity in isolated rat hepatocytes

1991 ◽  
Vol 273 (2) ◽  
pp. 485-488 ◽  
Author(s):  
V A Zammit ◽  
A M Caldwell
Keyword(s):  
Protein Kinase ◽  
Reductase Activity ◽  
Rat Hepatocytes ◽  
Total Activity ◽  
Isolated Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Hmg Coa Reductase ◽  
Lysosomal Proteolysis ◽  
Dependent Protein ◽  
Coa Reductase

The roles of protein kinase C, Ca2+/calmodulin-dependent protein kinase and AMP-activated protein kinase in the phosphorylation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase induced by Ca2(+)-mobilizing conditions in isolated hepatocytes were investigated. Only partial evidence for the involvement of AMP-activated kinase was found. Antagonism of calmodulin action prolonged the decrease in expressed/total activity ratio induced by vasopressin plus glucagon. Protease inhibitors active against Ca2(+)-dependent cytosolic proteases or lysosomal proteolysis did not attenuate the loss of total HMG-CoA reductase induced by glucagon plus vasopressin, but calmodulin antagonists largely prevented this effect.

Differential effects of dietary fat on chick plasma and liver composition and HMG-CoA reductase activity

1999 ◽  
Vol 10 (4) ◽  
pp. 198-204 ◽  
Author(s):  
Mercedes Castillo ◽  
José H Hortal ◽  
Almudena Gil-Villarino ◽  
Purificación Luque ◽  
José Iglesias ◽  
...  
Keyword(s):  
Dietary Fat ◽  
Reductase Activity ◽  
Hmg Coa Reductase ◽  
Differential Effects ◽  
Coa Reductase

scholarly journals Effect of portacaval anastomosis on hepatic HMG-CoA-reductase activity in normal rats

FEBS Letters ◽  
1977 ◽  
Vol 75 (1-2) ◽  
pp. 101-104 ◽  
Author(s):  
G.H. Bützow ◽  
F.W. Ossenberg ◽  
K. Becker ◽  
Chr. Schudt ◽  
U. Gaertner
Keyword(s):  
Reductase Activity ◽  
Portacaval Anastomosis ◽  
Hmg Coa Reductase ◽  
Coa Reductase
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