Increased production of apolipoprotein B-containing lipoproteins in the absence of hyperlipidemia in transgenic mice expressing cholesterol 7alpha-hydroxylase

The Journal of Biological Chemistry
Jon H MiyakeR A Davis

Abstract

The finding that expression of a cholesterol 7alpha-hydroxylase (CYP7A1) transgene in cultured rat hepatoma cells caused a coordinate increase in lipogenesis and secretion of apoB-containing lipoproteins led to the hypothesis that hepatic production of apoB-containing lipoproteins may be linked to the expression of CYP7A1 (Wang, S.-L., Du, E., Martin, T. D., and Davis, R. A. (1997) J. Biol. Chem. 272, 19351-19358). To examine this hypothesis in vivo, a transgene encoding CYP7A1 driven by the constitutive liver-specific enhancer of the human apoE gene was expressed in C56BL/6 mice. The expression of CYP7A1 mRNA (20-fold), protein ( approximately 10-fold), and enzyme activity (5-fold) was markedly increased in transgenic mice compared with non-transgenic littermates. The bile acid pool of CYP7A1 transgenic mice was doubled mainly due to increased hydrophobic dihydroxy bile acids. In CYP7A1 transgenic mice, livers contained approximately 3-fold more sterol response element-binding protein-2 mRNA. Hepatic expression of mRNAs encoding lipogenic enzymes (i.e. fatty-acid synthase, acetyl-CoA carboxylase, stearoyl-CoA desaturase, squalene synthase, farnesyl-pyrophosphate synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, and low densi...Continue Reading

References

Nov 1, 1992·Seminars in Liver Disease·D AmeisM C Schotz
Nov 1, 1992·Seminars in Liver Disease·Z R VlahcevicP B Hylemon
May 26, 1992·Biochemistry·D W Russell, K D Setchell
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·B AngelinJ D Brunzell
Jan 1, 1985·Journal of Cell Science. Supplement·J L Goldstein, M S Brown
Jan 1, 1984·The American Journal of Physiology·R L CurtisJ L Madara
Sep 15, 1995·The Journal of Biological Chemistry·G GuanI Shechter
Apr 1, 1995·Current Opinion in Lipidology·J Herz, T E Willnow
Feb 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·Z ShengJ L Goldstein
May 13, 1994·Biochimica Et Biophysica Acta·Z Yao, R S McLeod
Oct 1, 1995·Current Opinion in Lipidology·H N Ginsberg
Jan 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·J EricssonP A Edwards
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·J M LopezT F Osborne
Feb 7, 1997·The Journal of Biological Chemistry·J M LehmannT M Willson
Jul 1, 1997·The Proceedings of the Nutrition Society·R J Havel
Sep 20, 1997·The Journal of Biological Chemistry·M SchwarzD W Russell
Apr 4, 1998·The American Journal of Cardiology·G L Vega, S M Grundy
Apr 29, 1998·Current Opinion in Lipidology·M SchwarzD W Russell
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J D HortonH Shimano
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·M RaabeS G Young
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·B A JanowskiD J Mangelsdorf
May 21, 1999·Science·M MakishimaB Shan
May 21, 1999·Science·D J ParksJ M Lehmann
Jun 9, 1999·Molecular Cell·H WangB M Forman
Sep 11, 1999·Current Opinion in Lipidology·S O OlofssonJ Borén
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·M S Brown, J L Goldstein
Feb 23, 2000·The Journal of Clinical Investigation·J TwiskA D Attie
Mar 4, 2000·Gastroenterology·Z R VlahcevicW M Pandak

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Citations

Aug 19, 2007·Molecular BioSystems·Daniel A BlasioleAlan D Attie
Jun 28, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Silvia BijlandHans M G Princen
Nov 15, 2011·Journal of Cardiovascular Pharmacology·Jian ShenJosé M Ordovás
Jan 25, 2003·Annual Review of Biochemistry·David W Russell
Jan 13, 2006·Annual Review of Pharmacology and Toxicology·Frank J Gonzalez, Ai-Ming Yu
Feb 19, 2014·Current Opinion in Lipidology·Karen ReueLaurent Vergnes
Dec 20, 2005·The EMBO Journal·Ann-Hwee LeeLaurie H Glimcher
Jun 18, 2003·Journal of Lipid Research·B Ganesh BhatBradley T Keller
Feb 15, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tiangang LiJohn Y L Chiang
Jan 15, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Jon H MiyakeRoger A Davis
Nov 12, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Murray W HuffBradley T Keller
Feb 14, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Sabine M PostHans M G Princen
Jun 27, 2018·American Journal of Physiology. Endocrinology and Metabolism·Emmanuel SommNelly Pitteloud
Jul 31, 2014·Pharmacological Reviews·Tiangang Li, John Y L Chiang
Nov 8, 2002·The Journal of Biological Chemistry·Gilles LambertChristopher J Sinal
Jul 14, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tiangang LiJohn Y L Chiang
Sep 12, 2017·The Journal of Clinical Investigation·Elizabeth J TarlingThomas Q de Aguiar Vallim
Dec 31, 2003·Gastroenterology·Gerd A Kullak-UblickPeter J Meier

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