Cyp27a1

Summary

Gene Symbol: Cyp27a1
Description: cytochrome P450, family 27, subfamily a, polypeptide 1
Alias: 1300013A03Rik, Cyp27, sterol 26-hydroxylase, mitochondrial, 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 27-hydroxylase, cholesterol 27 hydroxylase, cytochrome P-450C27/25, cytochrome P450, 27a1, sterol 27-hydroxylase, vitamin D(3) 25-hydroxylase
Species: mouse
Products:     Cyp27a1

Top Publications

  1. Repa J, Lund E, Horton J, Leitersdorf E, Russell D, Dietschy J, et al. Disruption of the sterol 27-hydroxylase gene in mice results in hepatomegaly and hypertriglyceridemia. Reversal by cholic acid feeding. J Biol Chem. 2000;275:39685-92 pubmed
    Sterol 27-hydroxylase (CYP27) participates in the conversion of cholesterol to bile acids. We examined lipid metabolism in mice lacking the Cyp27 gene...
  2. Dubrac S, Lear S, Ananthanarayanan M, Balasubramaniyan N, Bollineni J, Shefer S, et al. Role of CYP27A in cholesterol and bile acid metabolism. J Lipid Res. 2005;46:76-85 pubmed
    ..Thus, both cyp27A genotype and gender affected the regulation of hepatic bile acid, cholesterol, and fatty acid metabolism. ..
  3. Escher G, Vögeli I, Escher R, Tuckey R, Erickson S, Krozowski Z, et al. Role of CYP27A1 in progesterone metabolism in vitro and in vivo. Am J Physiol Endocrinol Metab. 2009;297:E949-55 pubmed publisher
    ..using expression cloning in CHOP cells and a human kidney expression library, serendipitously cDNA encoding CYP27A1 was isolated...
  4. Båvner A, Shafaati M, Hansson M, Olin M, Shpitzen S, Meiner V, et al. On the mechanism of accumulation of cholestanol in the brain of mice with a disruption of sterol 27-hydroxylase. J Lipid Res. 2010;51:2722-30 pubmed publisher
    The rare disease cerebrotendinous xanthomatosis (CTX) is due to a lack of sterol 27-hydroxylase (CYP27A1) and is characterized by cholestanol-containing xanthomas in brain and tendons. Mice with the same defect do not develop xanthomas...
  5. Mateos L, Ismail M, Gil Bea F, Schule R, Schols L, Heverin M, et al. Side chain-oxidized oxysterols regulate the brain renin-angiotensin system through a liver X receptor-dependent mechanism. J Biol Chem. 2011;286:25574-85 pubmed publisher
    ..In contrast, brain RAS activity was decreased in Cyp27a1-deficient mice, a model exhibiting reduced 27-OH production from cholesterol...
  6. Ali Z, Heverin M, Olin M, Acimovic J, Lovgren Sandblom A, Shafaati M, et al. On the regulatory role of side-chain hydroxylated oxysterols in the brain. Lessons from CYP27A1 transgenic and Cyp27a1(-/-) mice. J Lipid Res. 2013;54:1033-43 pubmed publisher
    ..the present work, we utilized a previously described mouse model with overexpressed human sterol 27-hydroxylase (CYP27A1). The levels of 27OH were increased about 12-fold in the brain...
  7. Rosen H, Reshef A, Maeda N, Lippoldt A, Shpizen S, Triger L, et al. Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene. J Biol Chem. 1998;273:14805-12 pubmed
    ..Mice with a disrupted cyp27 (cyp27(-/-)) had normal plasma levels of cholesterol, retinol, tocopherol, and 1,25-dihydroxyvitamin D...
  8. Cali J, Russell D. Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis. J Biol Chem. 1991;266:7774-8 pubmed
  9. Li X, Pandak W, Erickson S, Ma Y, Yin L, Hylemon P, et al. Biosynthesis of the regulatory oxysterol, 5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes. J Lipid Res. 2007;48:2587-96 pubmed
    ..Assays using mitochondria isolated from rats and sterol 27-hydroxylase (Cyp27A1) gene knockout mice indicated that 25-hydroxycholesterol (25HC) is synthesized by CYP27A1...

More Information

Publications42

  1. Langston T, Hylemon P, Grogan W. Over-expression of hepatic neutral cytosolic cholesteryl ester hydrolase in mice increases free cholesterol and reduces expression of HMG-CoAR, CYP27, and CYP7A1. Lipids. 2005;40:31-8 pubmed
    ..These results demonstrate elevation of FC and depletion of cholesteryl esters by over-expression of hncCEH, which were resistant to compensatory responses by other enzymes of cholesterol homeostasis. ..
  2. Arnon R, Yoshimura T, Reiss A, Budai K, Lefkowitch J, Javitt N. Cholesterol 7-hydroxylase knockout mouse: a model for monohydroxy bile acid-related neonatal cholestasis. Gastroenterology. 1998;115:1223-8 pubmed
    ..The Cyp 7-/- knockout mouse mimics cholestatic events known to occur in humans and provides a unique opportunity for studying regulatory determinants. ..
  3. Heverin M, Maioli S, Pham T, Mateos L, Camporesi E, Ali Z, et al. 27-hydroxycholesterol mediates negative effects of dietary cholesterol on cognition in mice. Behav Brain Res. 2015;278:356-9 pubmed publisher
    ..To test this hypothesis we utilized Cyp27-/- mice lacking 27-hydroxycholesterol...
  4. Wang Y, Karu K, Meljon A, Turton J, Yau J, Seckl J, et al. 24S,25-Epoxycholesterol in mouse and rat brain. Biochem Biophys Res Commun. 2014;449:229-34 pubmed publisher
    ..By exploiting knockout mice for the enzyme oxysterol 7?-hydroxylase (Cyp7b1) we show that this enzymes is important for the subsequent metabolism of the 24S,25-epoxide. ..
  5. Vergnes L, Lee J, Chin R, Auwerx J, Reue K. Diet1 functions in the FGF15/19 enterohepatic signaling axis to modulate bile acid and lipid levels. Cell Metab. 2013;17:916-28 pubmed publisher
    ..Diet1 and FGF19 proteins exhibited overlapping subcellular localization in cultured intestinal cells. These results establish Diet1 as a control point in enterohepatic bile acid signaling and lipid homeostasis. ..
  6. Goodwin B, Gauthier K, Umetani M, Watson M, Lochansky M, Collins J, et al. Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci U S A. 2003;100:223-8 pubmed
    Sterol 27-hydroxylase (CYP27A1) is required for bile acid synthesis by both the classical and alternate pathways...
  7. Lyons M, Maeda N, Brown A. Paradoxical enhancement of hepatic metabolism of 7-ketocholesterol in sterol 27-hydroxylase-deficient mice. Biochim Biophys Acta. 2002;1581:119-26 pubmed
    ..In the present work, we utilised a mouse model possessing the null mutation in the sterol 27-hydroxylase gene, Cyp27, to further investigate the metabolism and potential arterial accumulation of 7KC versus cholesterol...
  8. Phan J, Pesaran T, Davis R, Reue K. The Diet1 locus confers protection against hypercholesterolemia through enhanced bile acid metabolism. J Biol Chem. 2002;277:469-77 pubmed
    ..Genetic analysis of serum bile acid levels revealed co-segregation with Diet1, indicating that this locus is likely responsible for both increased bile acid excretion and resistance to hypercholesterolemia in B6By mice...
  9. Stromstedt M, Keeney D, Waterman M, Paria B, Conley A, Dey S. Preimplantation mouse blastocysts fail to express CYP genes required for estrogen biosynthesis. Mol Reprod Dev. 1996;43:428-36 pubmed
    ..17 alpha-hydroxylase P450 (CYP17), cholesterol side-chain cleavage P450 (CYP11A1), sterol 27-hydroxylase P450 (CYP27), and aromatase P450 (CYP19) were examined in day 4 mouse blastocysts (day 1 = vaginal plug) and in day 13 and 16 ..
  10. Mast N, Anderson K, Lin J, Li Y, Turko I, Tatsuoka C, et al. Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum. J Biol Chem. 2017;292:4913-4924 pubmed publisher
    Cytochrome P450 27A1 (CYP27A1 or sterol 27-hydroxylase) is a ubiquitous, multifunctional enzyme catalyzing regio- and stereospecific hydroxylation of different sterols...
  11. Kovacs W, Shackelford J, Tape K, Richards M, Faust P, Fliesler S, et al. Disturbed cholesterol homeostasis in a peroxisome-deficient PEX2 knockout mouse model. Mol Cell Biol. 2004;24:1-13 pubmed
    ..The classic pathway of bile acid biosynthesis is downregulated in PEX2(-/-) mice. However, expression of CYP27A1, the rate-determining enzyme in the alternate pathway of bile acid synthesis, is upregulated threefold in the ..
  12. Zurkinden L, Solcà C, Vögeli I, Vogt B, Ackermann D, Erickson S, et al. Effect of Cyp27A1 gene dosage on atherosclerosis development in ApoE-knockout mice. FASEB J. 2014;28:1198-209 pubmed publisher
    In humans, sterol 27-hydroxylase (CYP27A1) deficiency leads to cholesterol deposition in tendons and vasculature...
  13. Saadane A, Mast N, Dao T, Ahmad B, Pikuleva I. Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells. J Biol Chem. 2016;291:20427-39 pubmed publisher
    ..unrecognized cholesterol-related pathway in the retina discovered during follow-up characterizations of Cyp27a1(-/-)Cyp46a1(-/-) mice...
  14. Schwarz M, Davis D, Vick B, Russell D. Genetic analysis of intestinal cholesterol absorption in inbred mice. J Lipid Res. 2001;42:1801-11 pubmed
  15. Bojanic D, Tarr P, Gale G, Smith D, Bok D, Chen B, et al. Differential expression and function of ABCG1 and ABCG4 during development and aging. J Lipid Res. 2010;51:169-81 pubmed publisher
    ..Finally, behavioral tests show that Abcg4(-/-) mice have a general deficit in associative fear memory. Together, these data indicate that loss of ABCG1 and/or ABCG4 from the CNS results in changes in metabolic pathways and in behavior...
  16. Li J, Daly E, Campioli E, Wabitsch M, Papadopoulos V. De novo synthesis of steroids and oxysterols in adipocytes. J Biol Chem. 2014;289:747-64 pubmed publisher
    ..The oxysterol 27-hydroxycholesterol (27HC), synthesized by the mitochondrial enzyme CYP27A1, was identified as one of the major de novo adipocyte products from cholesterol and its precursor mevalonate...
  17. Honda A, Salen G, Matsuzaki Y, Batta A, Xu G, Leitersdorf E, et al. Side chain hydroxylations in bile acid biosynthesis catalyzed by CYP3A are markedly up-regulated in Cyp27-/- mice but not in cerebrotendinous xanthomatosis. J Biol Chem. 2001;276:34579-85 pubmed
    ..inherited inborn error of bile acid synthesis caused by mutations in the mitochondrial sterol 27-hydroxylase (CYP27) gene. These bile alcohols may be intermediates in the alternative cholic acid side chain cleavage pathway...
  18. Vögeli I, Jung H, Dick B, Erickson S, Escher R, Funder J, et al. Evidence for a role of sterol 27-hydroxylase in glucocorticoid metabolism in vivo. J Endocrinol. 2013;219:119-29 pubmed publisher
    ..Sterol 27-hydroxylase (CYP27A1) catalyses the first step in the alternative pathway of bile acid synthesis by hydroxylating cholesterol to 27-..
  19. Sigurdsson V, Takei H, Soboleva S, Radulović V, Galeev R, Siva K, et al. Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver. Cell Stem Cell. 2016;18:522-32 pubmed publisher
    ..Taken together, these findings reveal that BA alleviation of ER stress is a mechanism required for HSC expansion during fetal hematopoiesis. ..
  20. Omarova S, Charvet C, Reem R, Mast N, Zheng W, Huang S, et al. Abnormal vascularization in mouse retina with dysregulated retinal cholesterol homeostasis. J Clin Invest. 2012;122:3012-23 pubmed publisher
    ..Cytochrome P450 27A1 (CYP27A1) is a ubiquitously expressed mitochondrial sterol 27-hydroxylase that plays an important role in the metabolism ..
  21. Meng Z, Liu N, Fu X, Wang X, Wang Y, Chen W, et al. Insufficient bile acid signaling impairs liver repair in CYP27(-/-) mice. J Hepatol. 2011;55:885-95 pubmed publisher
    ..Seventy percent partial hepatectomy (PH) and carbon tetrachloride (CCl(4)) treatment were performed using CYP27(-/-) mice, a genetic animal model with low BA levels...
  22. Zheng W, Mast N, Saadane A, Pikuleva I. Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments. J Lipid Res. 2015;56:81-97 pubmed publisher
  23. Inagaki T, Moschetta A, Lee Y, Peng L, Zhao G, Downes M, et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci U S A. 2006;103:3920-5 pubmed
  24. Saadane A, Mast N, Charvet C, Omarova S, Zheng W, Huang S, et al. Retinal and nonocular abnormalities in Cyp27a1(-/-)Cyp46a1(-/-) mice with dysfunctional metabolism of cholesterol. Am J Pathol. 2014;184:2403-19 pubmed publisher
    ..is tissue specific, and its significance has not yet been established for the retina, where cytochromes P450 (CYP27A1 and CYP46A1) are the major cholesterol-metabolizing enzymes...
  25. Hendrikx T, Jeurissen M, Bieghs V, Walenbergh S, van Gorp P, Verheyen F, et al. Hematopoietic overexpression of Cyp27a1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr(-/-) mice. J Hepatol. 2015;62:430-6 pubmed publisher
    ..The breakdown of free cholesterol inside Kupffer cells (KCs) by the mitochondrial enzyme CYP27A1 produces 27-hydroxycholesterol (27HC)...
  26. Ismail M, Mateos L, Maioli S, Merino Serrais P, Ali Z, Lodeiro M, et al. 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation. J Exp Med. 2017;214:699-717 pubmed publisher
    ..Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders. ..
  27. Zhu J, Ochalek J, Kaufmann M, Jones G, DeLuca H. CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo. Proc Natl Acad Sci U S A. 2013;110:15650-5 pubmed publisher
    ..These mice presented no health issues. A double knockout of Cyp2r1 and Cyp27a1 maintained a similar circulating level of 25-hydroxyvitamin D3 and 1?,25-dihydroxyvitamin D3...
  28. Lorbek G, Lewinska M, Rozman D. Cytochrome P450s in the synthesis of cholesterol and bile acids--from mouse models to human diseases. FEBS J. 2012;279:1516-33 pubmed publisher
    ..Unexpectedly, apparently normal Cyp27a1(-/-) mice still synthesize bile acids that originate from the compensatory pathway...
  29. DuSell C, Nelson E, Wang X, Abdo J, Mödder U, Umetani M, et al. The endogenous selective estrogen receptor modulator 27-hydroxycholesterol is a negative regulator of bone homeostasis. Endocrinology. 2010;151:3675-85 pubmed publisher
    ..More studies are warranted to fully elucidate the mechanism of action of 27HC in bone and to identify ways to modulate this pathway therapeutically. ..
  30. Meir K, Kitsberg D, Alkalay I, Szafer F, Rosen H, Shpitzen S, et al. Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis. J Biol Chem. 2002;277:34036-41 pubmed
    b>CYP27-overexpressed transgenic mice were generated with the use of a human full-length CYP27 coding region cloned into a ubiquitous expression vector...
  31. Honda A, Salen G, Matsuzaki Y, Batta A, Xu G, Leitersdorf E, et al. Differences in hepatic levels of intermediates in bile acid biosynthesis between Cyp27(-/-) mice and CTX. J Lipid Res. 2001;42:291-300 pubmed
    ..Patients with this disease are known to have mutations in the sterol 27-hydroxylase (Cyp27) gene...
  32. Cali J, Hsieh C, Francke U, Russell D. Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem. 1991;266:7779-83 pubmed
    ..In two unrelated patients with CTX, we have identified different point mutations in the gene (CYP27) encoding sterol 27-hydroxylase, a key enzyme in the bile acid biosynthesis pathway...
  33. Ferrell J, Boehme S, Li F, Chiang J. Cholesterol 7?-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders. J Lipid Res. 2016;57:1144-54 pubmed publisher