scholarly journals The Promoter of the Rat 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Contains a Tissue-Specific Estrogen-Responsive Region

1999 ◽  
Vol 13 (8) ◽  
pp. 1225-1236 ◽  
Author(s):  
Luciano Di Croce ◽  
Guillermo P. Vicent ◽  
Adali Pecci ◽  
Giovannella Bruscalupi ◽  
Anna Trentalance ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cell Lines ◽  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Hmg Coa Reductase ◽  
Tissue Specific ◽  
Reductase Gene ◽  
Responsive Element ◽  
Coa Reductase ◽  
Mcf 7

Abstract The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position −93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.

scholarly journals Developmental and metabolic regulation of the Drosophila melanogaster 3-hydroxy-3-methylglutaryl coenzyme A reductase.

1988 ◽  
Vol 8 (7) ◽  
pp. 2713-2721 ◽  
Author(s):  
F B Gertler ◽  
C Y Chiu ◽  
L Richter-Mann ◽  
D J Chin
Keyword(s):  
Drosophila Melanogaster ◽  
Metabolic Regulation ◽  
Coenzyme A ◽  
Terminal Region ◽  
Cdna Clones ◽  
Posttranslational Regulation ◽  
Hmg Coa Reductase ◽  
Reading Frame ◽  
Reductase Gene ◽  
Coa Reductase

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in Drosophila melanogaster 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 cloned the D. melanogaster HMG CoA reductase gene. The nucleotide sequence of the Drosophila HMG CoA reductase was determined from genomic and cDNA clones. A 2,748-base-pair open reading frame encoded a polypeptide of 916 amino acids (Mr, 98,165) that was similar to the hamster HMG CoA reductase. The C-terminal region had 56% identical residues and the N-terminal region had 7 potential transmembrane domains with 32 to 60% identical residues. In hamster HMG CoA reductase, the membrane regions were essential for posttranslational regulation. Since the Drosophila enzyme is not regulated by sterols, the strong N-terminal similarity was surprising. Two HMG CoA reductase mRNA transcripts, approximately 3.2 and 4 kilobases, were differentially expressed throughout Drosophila development. Mevalonate-fed Schneider cells showed a parallel reduction of both enzyme activity and abundance of the 4-kilobase mRNA transcript.

Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription

1994 ◽  
Vol 37 (15) ◽  
pp. 2343-2351 ◽  
Author(s):  
Scott D. Larsen ◽  
Charles H. Spilman ◽  
Yoshi Yagi ◽  
Dac M. Dinh ◽  
Karen L. Hart ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Coenzyme A ◽  
Hmg Coa Reductase ◽  
Design And Synthesis ◽  
Reductase Gene ◽  
Coa Reductase ◽  
Potential Inhibitors

scholarly journals Inhibition of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (Ex Vivo) by Morus indica (Mulberry)

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Vanitha Reddy Palvai ◽  
Asna Urooj
Keyword(s):  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Ex Vivo ◽  
Plasma Cholesterol ◽  
Effective Means ◽  
Inhibitory Effect ◽  
Hmg Coa Reductase ◽  
Standard Drug ◽  
Coa Reductase

Phytochemicals are the bioactive components that contribute to the prevention of cardiovascular and other degenerative diseases. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase would be an effective means of lowering plasma cholesterol in humans. The present study explores the HMG CoA reductase inhibitory effect of extracts from leaves of Morus indica varieties, M5, V1, and S36, compared with the statin, using an ex vivo method. The assay is based on the stoichiometric formation of coenzyme A during the reduction of microsomal HMG CoA to mevalonate. Dechlorophyllised extract of three varieties was studied at 300 µg. The coenzyme A released at the end of assay in control (100.31 nmoles) and statins (94.46 nm) was higher than the dechlorphyllised extracts of the samples. The coenzyme A released during the reduction of HMG CoA to mevalonate in dechlorophyllised extracts of the samples was as follows: S36 < M5 < V1. The results indicated that the samples were highly effective in inhibiting the enzyme compared to statins (standard drug). The results indicate the role of Morus varieties extracts in modulating the cholesterol metabolism by inhibiting the activity of HMG CoA reductase. These results provide scope for designing in vivo animal studies to confirm their effect.

Developmental and metabolic regulation of the Drosophila melanogaster 3-hydroxy-3-methylglutaryl coenzyme A reductase

1988 ◽  
Vol 8 (7) ◽  
pp. 2713-2721
Author(s):  
F B Gertler ◽  
C Y Chiu ◽  
L Richter-Mann ◽  
D J Chin
Keyword(s):  
Drosophila Melanogaster ◽  
Metabolic Regulation ◽  
Coenzyme A ◽  
Terminal Region ◽  
Cdna Clones ◽  
Posttranslational Regulation ◽  
Hmg Coa Reductase ◽  
Reading Frame ◽  
Reductase Gene ◽  
Coa Reductase

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in Drosophila melanogaster 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 cloned the D. melanogaster HMG CoA reductase gene. The nucleotide sequence of the Drosophila HMG CoA reductase was determined from genomic and cDNA clones. A 2,748-base-pair open reading frame encoded a polypeptide of 916 amino acids (Mr, 98,165) that was similar to the hamster HMG CoA reductase. The C-terminal region had 56% identical residues and the N-terminal region had 7 potential transmembrane domains with 32 to 60% identical residues. In hamster HMG CoA reductase, the membrane regions were essential for posttranslational regulation. Since the Drosophila enzyme is not regulated by sterols, the strong N-terminal similarity was surprising. Two HMG CoA reductase mRNA transcripts, approximately 3.2 and 4 kilobases, were differentially expressed throughout Drosophila development. Mevalonate-fed Schneider cells showed a parallel reduction of both enzyme activity and abundance of the 4-kilobase mRNA transcript.

Triazole resistant Aspergillus fumigatus in an Israeli patient with Chronic Cavitary Pulmonary Aspergillosis due to a novel E306K Substitution in Hmg1

2021 ◽  
Author(s):  
Mariana Handelman ◽  
Alma Morogovsky ◽  
Wei Liu ◽  
Ronen Ben-Ami ◽  
Nir Osherov
Keyword(s):  
Aspergillus Fumigatus ◽  
Coenzyme A ◽  
Pulmonary Aspergillosis ◽  
Hmg Coa Reductase ◽  
Therapeutic Challenge ◽  
Reductase Gene ◽  
Coa Reductase

Triazole resistance in the pathogenic mold Aspergillus fumigatus has increased worldwide, posing a growing therapeutic challenge. Recently, mutations in the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase gene ( hmg1 ) have been associated with triazole resistance. Here, we describe a novel E306K triazole resistance-conferring mutation in the HMG-CoA reductase gene from an Israeli patient with chronic cavitary pulmonary aspergillosis (CCPA).

scholarly journals Dietary modification of the activation state of intestinal 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase.

1984 ◽  
Vol 48 (11) ◽  
pp. 2745-2751
Author(s):  
Hirosuke OKU ◽  
Akira MORITA ◽  
Takashi IDE ◽  
Michihiro SUGANO
Keyword(s):  
Coenzyme A ◽  
Dietary Modification ◽  
Hmg Coa Reductase ◽  
Coa Reductase

scholarly journals Suppression of DNA synthesis by HMG-CoA reductase inhibitor in human hepatoma cell lines.

Kanzo ◽  
1989 ◽  
Vol 30 (5) ◽  
pp. 598-599
Author(s):  
Ryuzo SAITOH ◽  
Sumio KAWATA ◽  
Shinji TAMURA ◽  
Nobuyuki ITO ◽  
Kenji TAKAISHI ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Cell Lines ◽  
Reductase Inhibitor ◽  
Hepatoma Cell ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Hmg Coa Reductase ◽  
Hepatoma Cell Lines ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase
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