PL EN


Preferences help
enabled [disable] Abstract
Number of results
2009 | 56 | 2 | 279-289
Article title

Isolation and characterization of novel human short-chain dehydrogenase/reductase SCDR10B which is highly expressed in the brain and acts as hydroxysteroid dehydrogenase*

Content
Title variants
Languages of publication
EN
Abstracts
EN
Hydroxysteroid dehydrogenase belongs to the subfamily of short-chain dehydrogenases/reductases (SDR), and 11-β-hydroxysteroid dehydrogenase catalyzes the interconversion of inactive glucocorticoids (cortisone in human, dehydrocorticosterone in rodents) and active glucocorticoids (cortisol in human, corticosterone in rodents). We report here the cloning and characterization of a novel human SDR gene SCDR10B which encodes a protein with similarity to 11β-hydroxysteroid dehydrogenase 1. SCDR10B was isolated from a human brain cDNA library, and was mapped to chromosome 19p13.3 by browsing the UCSC genomic database. It contains an ORF with a length of 858 bp, encoding a protein with a transmembrane helix and SDR domain. Its molecular mass and isoelectric point are predicted to be 30.8 kDa and 10.3 kDa, respectively. SCDR10B protein is highly conserved in mammals and fish. Phylogenetic tree analysis indicated that SCDR10B stands for a new subgroup in the 11β-hydroxysteroid dehydrogenase family. Northern blot analysis showed that SCDR10B was highly expressed in brain, and a strong expression signal was detected in hippocampal neurons by immunohistochemical analysis. RT-PCR and immunohistochemical analysis showed that SCDR10B was up-regulated in lung-cancer cell lines and human lung cancer. SCDR10B can catalyze the dehydrogenation of cortisol in the presence of NADP+, and therefore it is a hydroxysteroid dehydrogenase.
Publisher

Year
Volume
56
Issue
2
Pages
279-289
Physical description
Dates
published
2009
received
2009-02-09
revised
2009-04-14
accepted
2009-04-28
(unknown)
2009-05-12
Contributors
author
  • State Key Laboratory of Genetic Engineering, The Institute of Genetics, Fudan University, Shanghai, People's Republic of China
author
  • State Key Laboratory of Genetic Engineering, The Institute of Genetics, Fudan University, Shanghai, People's Republic of China
author
  • Department of Phamacology, Soochow University, Suzhou, People's Republic of China
author
  • State Key Laboratory of Genetic Engineering, The Institute of Genetics, Fudan University, Shanghai, People's Republic of China
author
  • State Key Laboratory of Genetic Engineering, The Institute of Genetics, Fudan University, Shanghai, People's Republic of China
References
  • Arriza JL, Simerly RB, Swanson LW, Evans RM (1988) The neuronal mineralocorticoid receptor as a mediator of glucocorticoid response. Neuron 1: 887-900.
  • Audige A, Dick B, Frey BM, Frey FJ, Corman B, Vogt B (2002) Glucocorticoids and 11β-hydroxysteroid dehydrogenase type 2 gene expression in the aging kidney. Eur J Clin Invest 32: 411-420.
  • Baker ME (2004) Evolutionary analysis of 11β-hydroxysteroid dehydrogenase-type 1, -type 2, -type 3 and 17beta-hydroxysteroid dehydrogenase-type 2 in fish. FEBS Lett 574: 167-170.
  • Brereton PS, van Driel RR, Suhaimi F, Koyama K, Dilley R, Krozowski Z (2001) Light and electron microscopy localization of the 11β-hydroxysteroid dehydrogenase type I enzyme in the rat. Endocrinology 142: 1644-1651.
  • Bujalska IJ, Walker EA, Hewison M, Stewart PM (2002a) A switch in dehydrogenase to reductase activity of 11β-hydroxysteroid dehydrogenase type 1 upon differentiation of human omental adipose stromal cells. J Clin Endocrinol Metab 87: 1205-1210.
  • Bujalska IJ, Walker EA, Tomlinson JW, Hewison M, Stewart PM (2002b) 11β-hydroxysteroid dehydrogenase type 1 in differentiating omental human preadipocytes: from de-activation to generation of cortisol. Endocr Res 28: 449-461.
  • Cohen PG (2005) Estradiol induced inhibition of 11β-hydroxysteroid dehydrogenase 1: an explanation for the postmenopausal hormone replacement therapy effects. Med Hypotheses 64: 989-991.
  • De Kloet ER, Van Acker SA, Sibug RM, Oitzl MS, Meijer OC, Rahmouni K, de Jong W (2000) Brain mineralocorticoid receptors and centrally regulated functions. Kidney Int 57: 1329-1336.
  • Diaz R, Brown RW, Seckl JR (1998) Distinct ontogeny of glucocorticoid and mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase types I and II mRNAs in the fetal rat brain suggest a complex control of glucocorticoid actions. J Neurosci 18: 2570-2580.
  • Felsenstein J (1985) Confidence limits on phylogenics: an approach using the bootstrap. Evolution 39: 783-791.
  • Filling C, Berndt KD, Benach J, Knapp S, Prozorovski T, Nordling E, Ladenstein R, Jornvall H, Oppermann UC (2002) Critical residues for structure and catalysis in shortchain dehydrogenases/reductases. J Biol Chem 277: 25677-25684.
  • Funder JW (2005) Mineralocorticoid receptors: distribution and activation. Heart Fail Rev 10: 15-22.
  • Henderson BE, Feigelson HS (2000) Hormonal carcinogenesis. Carcinogenesis 21: 427-433.
  • Huang CQ, Zhou JL, Wu SL, Shan YX, Ten SL, Yu L (2004) Cloning and tissue distribution of the human B3GALT7 gene, a member of the β1,3-glycosyltransferase family. Glycoconj J 21: 267-273.
  • Jornvall H, Persson B, Krook M, Atrian S, Gonzalez-Duarte R, Jeffery J, Ghosh D (1995) Short-chain dehydrogenases/reductases (SDR). Biochemistry 34: 6003-6013.
  • Kallberg Y, Oppermann U, Jornvall H, Persson B (2002) Short-chain dehydrogenase/reductase (SDR) relationships: a large family with eight clusters common to human, animal, and plant genomes. Protein Sci 11: 636-641.
  • Kataoka S, Kudo A, Hirano H, Kawakami H, Kawano T, Higashihara E, Tanaka H, Delarue F, Sraer JD, Mune T, Krozowski ZS, Yan K (2002) 11β-hydroxysteroid dehydrogenase type 2 is expressed in the human kidney glomerulus. J Clin Endocrinol Metab 87: 877-882.
  • Kotelevtsev Y, Brown RW, Fleming S, Kenyon C, Edwards CR, Seckl JR, Mullins JJ (1999) Hypertension in mice lacking 11β-hydroxysteroid dehydrogenase type 2. J Clin Invest 103: 683-689.
  • Koyama K, Myles K, Smith R, Krozowski Z (2001) Expression of the 11β-hydroxysteroid dehydrogenase type II enzyme in breast tumors and modulation of activity and cell growth in PMC42 cells. J Steroid Biochem Mol Biol 76: 153-159.
  • Krozowski ZS, Stewart PM, Obeyesekere VR, Li K, Ferrari P (1997) Mutations in the 11β-hydroxysteroid dehydrogenase type II enzyme associated with hypertension and possibly stillbirth. Clin Exp Hypertens 19: 519-529.
  • Lin LJ, Tai S, Peng CC, Tzen J (2002) Steroleosin, a sterol-binding dehydrogenase in seed oil bodies. Plant Physiol 128: 1200-1211.
  • Lin-Su K, Zhou P, Arora N, Betensky BP, New MI, Wilson RC (2004) In vitro expression studies of a novel mutation delta299 in a patient affected with apparent mineralocorticoid excess. J Clin Endocrinol Metab 89: 2024-2027.
  • Nigawara T, Iwasaki Y, Asai M, Yoshida M, Kambayashi M, Sashinami H, Hashimoto K, Suda T (2006) Inhibition of 11β-hydroxysteroid dehydrogenase eliminates impaired glucocorticoid suppression and induces apoptosis in corticotroph tumor cells. Endocrinology 147: 769-772.
  • Oppermann UC, Filling C, Berndt KD, Persson B, Benach J, Ladenstein R, Jornvall H (1997) Active site directed mutagenesis of 3 beta/17 beta-hydroxysteroid dehydrogenase establishes differential effects on short-chain dehydrogenase/reductase reactions. Biochemistry 36: 34-40.
  • Ozols J (1995) Lumenal orientation and post-translational modifications of the liver microsomal 11β-hydroxysteroid dehydrogenase. J Biol Chem 270: 10360.
  • Patel PD, Sherman TG, Goldman DJ, Watson SJ (1989) Molecular cloning of a mineralocorticoid (type 1) receptor complementary DNA from rat hippcampus. Mol Endocrinol 3: 1877-1885.
  • Poletto R, Steibel JP, Siegford JM, Zanella AJ (2006) Effects of early weaning and social isolation on the expression of glucocorticoid and mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase 1 and 2 mRNAs in the frontal cortex and hippocampus of piglets. Brain Res 1067: 36-42.
  • Rabbitt EH, Lavery GG, Walker EA, Cooper MS, Stewart PM, Hewison M (2002) Prereceptor regulation of glucocorticoid action by 11β-hydroxysteroid dehydrogenase: a novel determinant of cell proliferation. Faseb J 16: 36-44.
  • Rabbitt EH, Gittoes NJ, Stewart PM, Hewison M (2003) 11β-hydroxysteroid dehydrogenases, cell proliferation and malignancy. J Steroid Biochem Mol Biol 85: 415-421.
  • Ricketts ML, Verhaeg JM, Bujalska I, Howie AJ, Rainey WE, Stewart PM (1998) Immunohistochemical localization of type 1 11β-hydroxysteroid dehydrogenase in human tissues. J Clin Endocrinol Metab 83: 1325-1335.
  • Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH (1999) Cortisol metabolism in human obesity: impaired cortisone→cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab 84: 1022-1027.
  • Tomlinson JW, Bujalska I, Stewart PM, Cooper MS (2000) The role of 11β-hydroxysteroid dehydrogenase in central obesity and osteoporosis. Endocr Res 26: 711-722.
  • Watzka M, Beyenburg S, Blumcke I, Elger CE, Bidlingmaier F, Stoffel-Wagner B (2000) Expression of mineralocorticoid and glucocorticoid receptor mRNA in the human hippocampus. Neurosci Lett 290: 121-124.
  • Wolf G (2002) Glucocorticoids in adipocytes stimulate visceral obesity. Nutr Rev 60: 148-151.
  • Zbankova S, Bryndova J, Kment M, Pacha J (2004) Expression of 11β-hydroxysteroid dehydrogenase types 1 and 2 in colorectal cancer. Cancer Lett 210: 95-100.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv56p279kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.