Overexpression of cholesterol transporter StAR increases in vivo rates of bile acid synthesis in the rat and mouse

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
S RenW M Pandak

Abstract

Bile acid synthesis (BAS) occurs mainly via two pathways: the "neutral" pathway, which is initiated by highly regulated microsomal CYP7A1, and an "acidic" pathway, which is initiated by mitochondrial CYP27A1. Previously, we have shown that overexpression of the steroidogenic acute regulatory protein (StAR), a mitochondrial cholesterol transport protein, increases bile acid biosynthesis more than 5-fold via the acidic pathway in primary rat hepatocytes. This observation suggests that mitochondrial cholesterol transport is the rate-limiting step of BAS via this pathway. The objective of this study was to determine the effect of increased StAR on rates of BAS in vivo. Overexpression of StAR and CYP7A1 were mediated via infection with recombinant adenoviruses. BAS rates were determined in chronic biliary-diverted rats and mice, and in mice with an intact enterohepatic circulation. The protein/messenger RNA levels of StAR and CYP7A1 increased dramatically following overexpression. Overexpression of StAR or CYP7A1 led to a similar 2-fold (P <.01) increase in BAS over up-regulated (approximately 2-fold) 3-day chronic biliary-diverted control rats. Additionally, overexpression of StAR led to more than 3- and 6-fold increases over contr...Continue Reading

Citations

Nov 15, 2007·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Laia VilàJuan Carlos Laguna
Jan 26, 2012·American Journal of Physiology. Endocrinology and Metabolism·Leyuan XuShunlin Ren
Oct 16, 2008·American Journal of Physiology. Endocrinology and Metabolism·Yongjie MaShunlin Ren
Apr 25, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Katie T BurkeLaura A Woollett
Apr 7, 2009·Journal of Lipid Research·Phillip B HylemonPaul Dent
Oct 4, 2011·The Journal of Endocrinology·Barbara J Clark
May 14, 2014·Steroids·Huiping Zhou, Phillip B Hylemon
Jun 27, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Xin ZhangShunlin Ren
Jul 13, 2007·Biochemical and Biophysical Research Communications·Shunlin RenWilliam M Pandak
Mar 10, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Silvana Zanlungo, Attilio Rigotti
May 3, 2005·Biochimica Et Biophysica Acta·E A HallW M Pandak
May 12, 2012·Toxicon : Official Journal of the International Society on Toxinology·S C ChaiK Jeyaseelan
Apr 6, 2006·Journal of Lipid Research·Xiaobo LiShunlin Ren

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