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The LXR-Idol axis differentially regulates plasma LDL levels in primates and mice.
Hong, Cynthia; Marshall, Stephanie M; McDaniel, Allison L; Graham, Mark; Layne, Joseph D; Cai, Lei; Scotti, Elena; Boyadjian, Rima; Kim, Jason; Chamberlain, Brian T; Tangirala, Rajendra K; Jung, Michael E; Fong, Loren; Lee, Richard; Young, Stephen G; Temel, Ryan E; Tontonoz, Peter.
Afiliação
  • Hong C; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Marshall SM; Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • McDaniel AL; Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • Graham M; Cardiovascular Antisense Drug Discovery Group, Isis Pharmaceuticals, Carlsbad, CA 92010, USA.
  • Layne JD; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, USA.
  • Cai L; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, USA.
  • Scotti E; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Boyadjian R; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kim J; Division of Endocrinology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Chamberlain BT; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Tangirala RK; Division of Endocrinology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Jung ME; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Fong L; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Lee R; Cardiovascular Antisense Drug Discovery Group, Isis Pharmaceuticals, Carlsbad, CA 92010, USA.
  • Young SG; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Temel RE; Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, USA. Electronic address: ryan.temel@uky.edu.
  • Tontonoz P; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ptontonoz@mednet.ucla.edu.
Cell Metab ; 20(5): 910-918, 2014 Nov 04.
Article em En | MEDLINE | ID: mdl-25440061
ABSTRACT
The LXR-regulated E3 ubiquitin ligase IDOL controls LDLR receptor stability independent of SREBP and PCSK9, but its relevance to plasma lipid levels is unknown. Here we demonstrate that the effects of the LXR-IDOL axis are both tissue and species specific. In mice, LXR agonist induces Idol transcript levels in peripheral tissues but not in liver, and does not change plasma LDL levels. Accordingly, Idol-deficient mice exhibit elevated LDLR protein levels in peripheral tissues, but not in the liver. By contrast, LXR activation in cynomolgus monkeys induces hepatic IDOL expression, reduces LDLR protein levels, and raises plasma LDL levels. Knockdown of IDOL in monkeys with an antisense oligonucleotide blunts the effect of LXR agonist on LDL levels. These results implicate IDOL as a modulator of plasma lipid levels in primates and support further investigation into IDOL inhibition as a potential strategy for LDL lowering in humans.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Ubiquitina-Proteína Ligases / Receptores Nucleares Órfãos / LDL-Colesterol / Fígado Limite: Animals / Humans / Male Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA
Texto completo
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Ubiquitina-Proteína Ligases / Receptores Nucleares Órfãos / LDL-Colesterol / Fígado Limite: Animals / Humans / Male Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA