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

Identifieur interne : 000457 ( Istex/Corpus ); précédent : 000456; suivant : 000458

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

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

Source :

Biochemical and Biophysical Research Communications [ 0006-291X ] ; 1999.

RBID : ISTEX:680A1161AD2C1C6EDA86FF83EBC2377049E3D94F

Abstract

The ability of two 15-ketosubstituted sterols, 5α-cholest-8(14)-en-3β-ol-15-one and 3β-(2-hydroxyethoxy)-5α-cholest-8(14)-en-15-one, to alter the mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase, low density lipoprotein receptor, and oxysterol binding protein was studied and compared with the effects of 25-hydroxycholesterol in Hep G2 cells. All three oxysterols decreased the level of HMG CoA reductase mRNA at concentrations of 10–30 μM, although 25-hydroxycholesterol was effective at concentrations of 1–3 μM. 25-Hydroxycholesterol lowered the level of LDL receptor mRNA more efficiently after 8 hours than after 24 hours of incubation, whereas 15-ketosterols did not decrease the mRNA level of the LDL receptor. The transcriptions of HMG CoA reductase and LDL receptor genes are therefore independently regulated by 15-ketosterols in Hep G2 cells. In addition, the level of the oxysterol binding protein mRNA is not affected by oxysterols in Hep G2 cells.

Url:

https://api.istex.fr/document/680A1161AD2C1C6EDA86FF83EBC2377049E3D94F/fulltext/pdf

DOI: 10.1006/bbrc.1999.0844

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ISTEX:680A1161AD2C1C6EDA86FF83EBC2377049E3D94F

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<notesStmt><note>Abbreviations used: CK15, 3β-(2-hydroxyethoxy)-5α-cholest-8(14)-en-15-one; K15, 5α-cholest-8(14)-en-3β-ol-15-one; LPDS, lipoprotein-deficient serum; MMLV, Moloney murine leukaemia virus; OSBP, oxysterol binding protein; SRE, sterol regulatory element; SREBP, sterol regulatory element binding protein; SCAP, SREBP cleavage activating protein</note>
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<abstract xml:lang="en"><p>The ability of two 15-ketosubstituted sterols, 5α-cholest-8(14)-en-3β-ol-15-one and 3β-(2-hydroxyethoxy)-5α-cholest-8(14)-en-15-one, to alter the mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase, low density lipoprotein receptor, and oxysterol binding protein was studied and compared with the effects of 25-hydroxycholesterol in Hep G2 cells. All three oxysterols decreased the level of HMG CoA reductase mRNA at concentrations of 10–30 μM, although 25-hydroxycholesterol was effective at concentrations of 1–3 μM. 25-Hydroxycholesterol lowered the level of LDL receptor mRNA more efficiently after 8 hours than after 24 hours of incubation, whereas 15-ketosterols did not decrease the mRNA level of the LDL receptor. The transcriptions of HMG CoA reductase and LDL receptor genes are therefore independently regulated by 15-ketosterols in Hep G2 cells. In addition, the level of the oxysterol binding protein mRNA is not affected by oxysterols in Hep G2 cells.</p>
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<ce:note-para>Abbreviations used: CK15, 3β-(2-hydroxyethoxy)-5α-cholest-8(14)-en-15-one; K15, 5α-cholest-8(14)-en-3β-ol-15-one; LPDS, lipoprotein-deficient serum; MMLV, Moloney murine leukaemia virus; OSBP, oxysterol binding protein; SRE, sterol regulatory element; SREBP, sterol regulatory element binding protein; SCAP, SREBP cleavage activating protein</ce:note-para>
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<ce:abstract-sec><ce:simple-para view="all" id="simple-para.0010">The ability of two 15-ketosubstituted sterols, 5α-cholest-8(14)-en-3β-ol-15-one and 3β-(2-hydroxyethoxy)-5α-cholest-8(14)-en-15-one, to alter the mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase, low density lipoprotein receptor, and oxysterol binding protein was studied and compared with the effects of 25-hydroxycholesterol in Hep G2 cells. All three oxysterols decreased the level of HMG CoA reductase mRNA at concentrations of 10–30 μM, although 25-hydroxycholesterol was effective at concentrations of 1–3 μM. 25-Hydroxycholesterol lowered the level of LDL receptor mRNA more efficiently after 8 hours than after 24 hours of incubation, whereas 15-ketosterols did not decrease the mRNA level of the LDL receptor. The transcriptions of HMG CoA reductase and LDL receptor genes are therefore independently regulated by 15-ketosterols in Hep G2 cells. In addition, the level of the oxysterol binding protein mRNA is not affected by oxysterols in Hep G2 cells.</ce:simple-para>
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<abstract lang="en">The ability of two 15-ketosubstituted sterols, 5α-cholest-8(14)-en-3β-ol-15-one and 3β-(2-hydroxyethoxy)-5α-cholest-8(14)-en-15-one, to alter the mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase, low density lipoprotein receptor, and oxysterol binding protein was studied and compared with the effects of 25-hydroxycholesterol in Hep G2 cells. All three oxysterols decreased the level of HMG CoA reductase mRNA at concentrations of 10–30 μM, although 25-hydroxycholesterol was effective at concentrations of 1–3 μM. 25-Hydroxycholesterol lowered the level of LDL receptor mRNA more efficiently after 8 hours than after 24 hours of incubation, whereas 15-ketosterols did not decrease the mRNA level of the LDL receptor. The transcriptions of HMG CoA reductase and LDL receptor genes are therefore independently regulated by 15-ketosterols in Hep G2 cells. In addition, the level of the oxysterol binding protein mRNA is not affected by oxysterols in Hep G2 cells.</abstract>
<note>Abbreviations used: CK15, 3β-(2-hydroxyethoxy)-5α-cholest-8(14)-en-15-one; K15, 5α-cholest-8(14)-en-3β-ol-15-one; LPDS, lipoprotein-deficient serum; MMLV, Moloney murine leukaemia virus; OSBP, oxysterol binding protein; SRE, sterol regulatory element; SREBP, sterol regulatory element binding protein; SCAP, SREBP cleavage activating protein</note>
<note type="content">Section title: Regular Article</note>
<relatedItem type="host"><titleInfo><title>Biochemical and Biophysical Research Communications</title>
</titleInfo>
<titleInfo type="abbreviated"><title>YBBRC</title>
</titleInfo>
<originInfo><dateIssued encoding="w3cdtf">19990616</dateIssued>
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<identifier type="ISSN">0006-291X</identifier>
<identifier type="PII">S0006-291X(00)X0117-9</identifier>
<part><date>19990616</date>
<detail type="volume"><number>259</number>
<caption>vol.</caption>
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<detail type="issue"><number>3</number>
<caption>no.</caption>
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<extent unit="issue pages"><start>505</start>
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<extent unit="pages"><start>688</start>
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<identifier type="istex">680A1161AD2C1C6EDA86FF83EBC2377049E3D94F</identifier>
<identifier type="DOI">10.1006/bbrc.1999.0844</identifier>
<identifier type="PII">S0006-291X(99)90844-6</identifier>
<identifier type="ArticleID">90844</identifier>
<recordInfo><recordOrigin>ELSEVIER</recordOrigin>
<recordContentSource>Academic Press, ©1999</recordContentSource>
</recordInfo>
</mods>
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HMG CoA Reductase and LDL Receptor Genes Are Regulated Differently by 15-Ketosterols in Hep G2 Cells

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

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