HMG CoA Reductase and LDL Receptor Genes Are Regulated Differently by 15-Ketosterols in Hep G2 Cells

Kisseleva, Anastassia F.; Goryunova, Ludmila E.; Planells, Richard; Lafont, Huguette; Alquier, Christian

doi:10.1006/bbrc.1999.0844

Cited by 6 publications

(4 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, coordinated transcriptional regulation of the LDLR and HMGCR genes by sterols has been reported [26] . The transcriptional regulator 25OH has been shown to regulate cholesterol metabolism by repressing the synthesis of the HMGCR [27] and LDLR genes [26] . This observation is of particular importance since the clearance of serum cholesterol is mediated by LDLR and thus the optimal hypocholesterolemic drug should suppress HMGCR activity without lowering LDLR levels.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Low-Density Lipoprotein Receptor and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Expression by Thymoquinone-Rich Fraction and Thymoquinone in HepG2 Cells

Al-Naqeep¹,

Ismail²,

Allaudin

2009

Lifestyle Genomics

View full text Add to dashboard Cite

Background and Aim: Nigella sativa and its active constituent thymoquinone (TQ) have been exploited for their various health benefits. This work was aimed to investigate the regulatory effects of TQ-rich fraction (TQRF) and commercial TQ on the low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) genes in HepG2 cells. Methods and Results: TQRF was extracted from N. sativa seeds using supercritical fluid extraction. The regulatory effects of TQRF at 80 μg/ml and TQ at 2 μg/ml on LDLR and HMGCR gene expression were investigated in HepG2 cells using quantitative real-time PCR. The TQ content in TQRF was 2.77% (w/w) and was obtained at a temperature of 40°C and a pressure of 600 bar. Treatment of cells with TQRF and TQ resulted in a 7- and 2-fold upregulation of LDLR mRNA level, respectively, compared with untreated cells. The mRNA level of HMGCR was downregulated by 71 and 12%, respectively, compared with untreated cells. Conclusion: TQRF and TQ regulated genes involved in cholesterol metabolism by two mechanisms, the uptake of low-density lipoprotein cholesterol via the upregulation of the LDLR gene and inhibition of cholesterol synthesis via the suppression of the HMGCR gene.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of Low-Density Lipoprotein Receptor and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Expression by Thymoquinone-Rich Fraction and Thymoquinone in HepG2 Cells

Al-Naqeep¹,

Ismail²,

Allaudin

2009

Lifestyle Genomics

View full text Add to dashboard Cite

show abstract

“…The levels of HMGCR mRNA are reduced by procaine (Xu et al, 2003), fenofibrate, a potent hypolipidemic agent (Guo et al, 2001), oxysterols (Kisseleva et al, 1999), monoterpenes (Peffley and Gayen, 2003), cholesterol-enriched diet and starvation (Sato et al, 2003); conversely, they are increased by pathological conditions, such as tumors (Hentosh et al, 2001) and renal failure (Chmielewski et al, 2003), by Cu 2+ exposure (Svensson et al, 2003), growth hormone (Machado et al, 2003) and red wine (Pal et al, 2003). Moreover, the expression of HSP and HMGCR resulted increased after heat shock (Zager and Johnson, 2001), as well as after crowding stress as shown by our experiments of quantitative PCR.…”

Section: Discussionmentioning

confidence: 99%

Molecular markers for animal biotechnology: sea bass (Dicentrarchus labrax, L.) HMG-CoA reductase mRNA

Gornati

Papis

Rimoldi

et al. 2005

Gene

View full text Add to dashboard Cite

“…Abnormal lipid and lipoprotein metabolism can result in dyslipidemia, including elevated plasma cholesterol and/or TG levels and reduced HDL levels, which contribute to the increased prevalence of morbid obesity. Several proteins associated with dyslipidemia have been reported to play crucial roles in lipogenesis, including fatty acid synthase (FAS), , sterol regulatory element-binding proteins (SREBPs), and 3-hydroxy-3-methylglutaryl -coenzyme A reductase (HMG-CoA reductase), − and the expression levels of these enzymes are dynamic in response to cellular energy status. Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA in a biotin-dependent manner .…”

Section: Introductionmentioning

confidence: 99%

Solanum nigrum Polyphenol Extracts Inhibit Hepatic Inflammation, Oxidative Stress, and Lipogenesis in High-Fat-Diet-Treated Mice

Chang

Chung

Lee

et al. 2017

J. Agric. Food Chem.

View full text Add to dashboard Cite

Patients with diabetes, obesity, and hyperlipidemia are all high-risk groups for fatty liver; however, the mechanism of fatty liver formation is not completely understood. Studies have indicated that abnormal fat metabolism, oxidative stress, and insulin resistance are positively correlated with peroxidation and abnormal cytokine production. Recent studies have revealed that Solanum nigrum extracts (SNE) possess anti-inflammatory, antioxidation, antihyperlipidemia, and liver protection abilities. Therefore, the present study investigated the in vivo and in vitro effects of an SNE on nonalcoholic fatty liver (NAFL)-induced hepatitis. In vivo data demonstrated that the SNE reduced blood triglyceride, sugar, and cholesterol levels, as well as fat accumulation, oxidative stress, and lipid peroxidation in high-fat-diet-treated mice. The results indicated that the SNE downregulated the expression of fatty acid synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and sterol regulatory element-binding proteins (SREBPs) through the AMP-activated protein kinase (AMPK) pathway and upregulated the expression of carnitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-activated receptor alpha. Furthermore, we prepared a Solanum nigrum polyphenol extract (SNPE) from the SNE; the SNPE reduced hepatic lipid (oleic acid) accumulation. Therefore, SNE have the potential to alleviate NAFL-induced hepatitis, and polyphenolic compounds are the main components of SNE. Moreover, SNE can be used to develop health-food products for preventing NAFL disease.

show abstract

HMG CoA Reductase and LDL Receptor Genes Are Regulated Differently by 15-Ketosterols in Hep G2 Cells

Cited by 6 publications

References 33 publications

Regulation of Low-Density Lipoprotein Receptor and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Expression by Thymoquinone-Rich Fraction and Thymoquinone in HepG2 Cells

Regulation of Low-Density Lipoprotein Receptor and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Expression by Thymoquinone-Rich Fraction and Thymoquinone in HepG2 Cells

Molecular markers for animal biotechnology: sea bass (Dicentrarchus labrax, L.) HMG-CoA reductase mRNA

Solanum nigrum Polyphenol Extracts Inhibit Hepatic Inflammation, Oxidative Stress, and Lipogenesis in High-Fat-Diet-Treated Mice

Contact Info

Product

Resources

About