Identification of a novel sulfonated oxysterol, 5-cholesten-3beta,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria.

Journal of Lipid Research
Shunlin RenWilliam M Pandak

Abstract

This study reports the discovery of a novel sulfonated oxysterol found at high levels in the mitochondria and nuclei of primary rat hepatocytes after overexpression of the gene encoding steroidogenic acute regulatory protein (StarD1). Forty-eight hours after infection of primary rat hepatocytes with recombinant adenovirus encoding StarD1, rates of bile acid synthesis increased by 4-fold. Concurrently, [(14)C]cholesterol metabolites (oxysterols) were increased dramatically in both the mitochondria and nuclei of StarD1-overexpressing cells, but not in culture medium. A water-soluble [(14)C]oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Enzymatic digestion, HPLC, and tandem mass spectrometry analysis identified the water-soluble oxysterol as 5-cholesten-3beta,25-diol 3-sulfonate. Further experiments detected this cholesterol metabolite in the nuclei of normal human liver tissues. Based upon these observations, we hypothesized a new pathway by which cholesterol is metabolized in the mitochondrion.

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Citations

Feb 12, 2009·Molecular & Cellular Proteomics : MCP·Anthony C Smith, Alan J Robinson
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
May 14, 2014·Steroids·Huiping Zhou, Phillip B Hylemon
Jun 27, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Xin ZhangShunlin Ren
Jan 8, 2016·Annual Review of Pharmacology and Toxicology·Winnie LuuAndrew J Brown
Jul 13, 2007·Biochemical and Biophysical Research Communications·Shunlin RenWilliam M Pandak
Jul 17, 2015·Canadian Journal of Microbiology·Ragunath SingaraveluJohn Paul Pezacki
May 18, 2012·Metabolism: Clinical and Experimental·Ji-Young Cha, Young-Bum Kim
Sep 12, 2015·IEEE Transactions on Visualization and Computer Graphics· Junhui Hou Ying He
Apr 6, 2006·Journal of Lipid Research·Xiaobo LiShunlin Ren
Mar 10, 2007·Journal of Lipid Research·Hirotoshi FudaCharles A Strott
Dec 5, 2013·American Journal of Physiology. Endocrinology and Metabolism·Shunlin Ren, Yanxia Ning
Jul 14, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Irundika Hk DiasPablo Martinez-Lage

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