In Vivo LDL Receptor and HMG-CoA Reductase Regulation in Human Lymphocytes and Its Alterations During Aging

Asian plantain (Plantago asiatica) essential oil (PAEO) contains multiple bioactive compounds, but its potential effects on lipid metabolism have not been examined. PAEO was found to be mostly composed of oxygenated monoterpenes, with linalool as the major component (82·5 %, w/w), measured using GC–MS. Incubation of 0–200 μg PAEO/ml with HepG2 cells for 24 h resulted in no significant toxicity. Incubation with 0·2 mg PAEO/ml altered the expression of LDL receptor (+83 %; P < 0·05) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase ( − 37 %; P < 0·05), as assessed using RT-PCR. LDL oxidation was markedly inhibited by PAEO treatment due to the prevalence of linalool compounds in PAEO. Oral administration of PAEO for 3 weeks in C57BL/6 mice significantly reduced plasma total cholesterol and TAG concentrations by 29 and 46 %, respectively. The mRNA (+58 %; P < 0·05), but not protein, levels of the LDL receptor were significantly higher, whereas both mRNA and protein levels of HMG-CoA reductase were significantly lower ( − 46 and − 11 %, respectively; P < 0·05) in the liver of PAEO-fed than of control mice. The mRNA levels of CYP7A1 were marginally reduced in HepG2 cells, but not in mouse liver after PAEO treatment. Thus, PAEO may have hypocholesterolaemic effects by altering the expression of HMG-CoA reductase. Reduced TAG and oxidised LDL may provide additional cardiovascular protective benefits.

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Glycation and HMG-CoA Reductase Inhibitors: Implication in Diabetes and Associated Complications

Current Diabetes Reviews ◽

10.2174/1573399814666180924113442 ◽

2019 ◽

Vol 15 (3) ◽

pp. 213-223 ◽

Cited By ~ 3

Author(s):

Rabia Nabi ◽

Sahir Sultan Alvi ◽

Mohd. Saeed ◽

Saheem Ahmad ◽

Mohammad Salman Khan

Keyword(s):

Oxidized Ldl ◽

Advanced Glycation Endproducts ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Protective Role ◽

Therapeutic Effects ◽

Hmg Coa Reductase ◽

Toxicological Effects ◽

Coa Reductase

Introduction: Diabetes Mellitus (DM) acts as an absolute mediator of cardiovascular risk, prompting the prolonged occurrence, size and intricacy of atherosclerotic plaques via enhanced Advanced Glycation Endproducts (AGEs) formation. Moreover, hyperglycemia is associated with enhanced glyco-oxidized and oxidized Low-Density Lipoprotein (LDL) possessing greater atherogenicity and decreased the ability to regulate HMG-CoA reductase (HMG-R). Although aminoguanidine (AG) prevents the AGE-induced protein cross-linking due to its anti-glycation potential, it exerts several unusual pharmaco-toxicological effects thus restraining its desirable therapeutic effects. HMG-R inhibitors/statins exhibit a variety of beneficial impacts in addition to the cholesterol-lowering effects. Objective: Inhibition of AGEs interaction with receptor for AGEs (RAGE) and glyco-oxidized-LDL by HMG-R inhibitors could decrease LDL uptake by LDL-receptor (LDL-R), regulate cholesterol synthesis via HMG-R, decrease oxidative and inflammatory stress to improve the diabetes-associated complications. Conclusion: Current article appraises the pathological AGE-RAGE concerns in diabetes and its associated complications, mainly focusing on the phenomenon of both circulatory AGEs and those accumulating in tissues in diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy, discussing the potential protective role of HMG-R inhibitors against diabetic complications.

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The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-β1–42 in the rat hippocampus in vivo

Neuropharmacology ◽

10.1016/j.neuropharm.2006.07.031 ◽

2007 ◽

Vol 52 (1) ◽

pp. 136-145 ◽

Cited By ~ 50

Author(s):

Rachael M. Clarke ◽

Florence O'Connell ◽

Anthony Lyons ◽

Marina A. Lynch

Keyword(s):

Reductase Inhibitor ◽

Rat Hippocampus ◽

Acute Administration ◽

Hmg Coa Reductase ◽

Hmg Coa Reductase Inhibitor ◽

Coa Reductase

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Regulation of HMG-CoA reductase, apoprotein-B and LDL receptor gene expression by the hypocholesterolemic drugs simvastatin and ciprofibrate in Hep G2, human and rat hepatocytes

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(92)90201-6 ◽

1992 ◽

Vol 1127 (1) ◽

pp. 57-66 ◽

Cited By ~ 33

Author(s):

Wen Qin ◽

Jacqueline Infante ◽

Shu-Ren Wang ◽

Recaredo Infante

Keyword(s):

Gene Expression ◽

Receptor Gene ◽

Ldl Receptor ◽

Rat Hepatocytes ◽

Hep G2 ◽

Hmg Coa Reductase ◽

Apoprotein B ◽

Coa Reductase ◽

Receptor Gene Expression ◽

Hypocholesterolemic Drugs

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The LDL Receptor and HMG-CoA Reductase — Two Membrane Molecules That Regulate Cholesterol Homeostasis

Modulation by Molecular Interactions - Current Topics in Cellular Regulation - Current Topics in Cellular Regulation ◽

10.1016/b978-0-12-152826-3.50008-5 ◽

1985 ◽

pp. 3-15 ◽

Cited By ~ 23

Author(s):

Michael S. Brown ◽

Joseph L. Goldstein

Keyword(s):

Ldl Receptor ◽

Cholesterol Homeostasis ◽

Hmg Coa Reductase ◽

Coa Reductase

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The effect of (−)-hydroxycitrate on the activity of the low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2

Biochemical Journal ◽

10.1042/bj2720181 ◽

1990 ◽

Vol 272 (1) ◽

pp. 181-186 ◽

Cited By ~ 44

Author(s):

T A Berkhout ◽

L M Havekes ◽

N J Pearce ◽

P H E Groot

Keyword(s):

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Low Density ◽

Hep G2 ◽

Atp Citrate Lyase ◽

Hmg Coa Reductase ◽

Synthetic Pathway ◽

Citrate Lyase ◽

Coa Reductase

(-)-Hydroxycitrate, a potent inhibitor of ATP citrate-lyase, was tested in Hep G2 cells for effects on cholesterol homoeostasis. After 2.5 h and 18 h incubations with (-)-hydroxycitrate at concentrations of 0.5 mM or higher, incorporation of [1,5-14C]citrate into fatty acids and cholesterol was strongly inhibited. This most likely reflects an effective inhibition of ATP citrate-lyase. Cholesterol biosynthesis was decreased to 27% of the control value as measured by incorporations from 3H2O, indicating a decreased flux of carbon units through the cholesterol-synthetic pathway. After 18 h preincubation with 2 mM-(-)-hydroxycitrate, the cellular low-density-lipoprotein (LDL) receptor activity was increased by 50%, as determined by the receptor-mediated association and degradation. Measurements of receptor-mediated binding versus LDL concentration suggests that this increase was due to an increase in the numbers of LDL receptors. Simultaneously, enzyme levels of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase as determined by activity measurements increased 30-fold. Our results suggest that the increases in HMG-CoA reductase and the LDL receptor are initiated by the decreased flux of carbon units in the cholesterol-synthetic pathway, owing to inhibition of ATP citratelyase. A similar induction of HMG-CoA reductase and LDL receptor was also found after preincubations of cells with 0.3 microM-mevinolin, suggesting that the underlying mechanism for this induction is identical for both drugs.

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