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Human dehydrogenase/reductase (SDR family) member 8 (DHRS8): a description and evaluation of its biochemical properties

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Abstract

Dehydrogenase/reductase (SDR family) member 8 (DHRS8, SDR16C2) belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, one of the largest enzyme groups. In addition to the well-known members which participate in the metabolism of important eobiotics and xenobiotics, this superfamily contains many poorly characterized proteins. DHRS8 is a member of the Multisubstrate NADP(H)-dependent SDR16C family, which generally contains insufficiently described enzymes. Despite the limited knowledge about DHRS8, preliminary indicators have emerged regarding its significant function in the modulation of steroidal activity, at least in the case of 3α-adiol, lipid metabolism and detoxification. The aim of this study was to describe additional biochemical properties of DHRS8 and to unify knowledge about this enzyme. The DHRS8 was prepared in recombinant form and its membrane topology in the endoplasmic reticulum as an integral protein with cytosolic orientation was demonstrated. The enzyme participates in the NAD+-dependent oxidation of steroid hormones as β-estradiol and testosterone in vitro; apparent K m and V max values were 39.86 µM and 0.80 nmol × mg−1 × min−1 for β-estradiol and 1207.29 µM and 3.45 nmol × mg−1 × min−1 for testosterone. Moreover, synthetic steroids (methyltestosterone and nandrolone) used as anabolics as well as all-trans-retinol were for the first time identified as substrates of DHRS8. This knowledge of its in vitro activity together with a newly described expression pattern at the protein level in tissues involved in steroidogenesis (adrenal gland and testis) and detoxification (liver, lung, kidney and small intestine) could suggest a potential role of DHRS8 in vivo.

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Abbreviations

SDR:

Short-chain dehydrogenases/reductases

DHRS8:

Dehydrogenase/reductase (SDR family) member 8

17β-HSD11:

17β-Hydroxysteroid dehydrogenase type 11

retSDR2:

Retinal short-chain dehydrogenase/reductase 2

Sf9-Mi-DHRS8:

Sf9 microsomes containing overexpressed DHRS8

3α-diol:

5α-Androstane-3α,17β-diol

a-dione:

4-Androstene-3,17-dione

ER:

Endoplasmic reticulum

TM:

Transmembrane

References

  1. Li KXZ, Smith RE, Krozowski ZS (1998) Cloning and expression of a novel tissue specific 17β-hydroxysteroid dehydrogenase. Endocr Res 24:663–667

    Article  CAS  PubMed  Google Scholar 

  2. Chai Z, Brereton P, Suzuki T et al (2003) 17β-Hydroxysteroid dehydrogenase type XI localizes to human steroidogenic cells. Endocrinology 144:2084–2091. doi:10.1210/en.2002-221030

    Article  CAS  PubMed  Google Scholar 

  3. Bray JE, Marsden BD, Oppermann U (2009) The human short-chain dehydrogenase/reductase (SDR) superfamily: a bioinformatics summary. Chem Biol Interact 178:99–109. doi:10.1016/j.cbi.2008.10.058

    Article  CAS  PubMed  Google Scholar 

  4. Persson B, Kallberg Y (2013) Classification and nomenclature of the superfamily of short-chain dehydrogenases/reductases (SDRs). Chem Biol Interact 202(1):111–115

    Article  CAS  PubMed  Google Scholar 

  5. Lee S-A, Belyaeva OV, Kedishvili NY (2009) Biochemical characterization of human epidermal retinol dehydrogenase 2. Chem Biol Interact 178:182–187. doi:10.1016/j.cbi.2008.09.019

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Wu BX, Moiseyev G, Chen Y et al (2004) Identification of RDH10, an all-trans retinol dehydrogenase, in retinal Müller cells. Investig Ophthalmol Vis Sci 45:3857–3862. doi:10.1167/iovs.03-1302

    Article  Google Scholar 

  7. Haeseleer F, Huang J, Lebioda L et al (1998) Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal. J Biol Chem 273:21790–21799

    Article  CAS  PubMed  Google Scholar 

  8. Belyaeva OV, Lee SA, Adams MK et al (2012) Short chain dehydrogenase/reductase Rdhe2 is a novel retinol dehydrogenase essential for frog embryonic development. J Biol Chem 287:9061–9071. doi:10.1074/jbc.M111.336727

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Belyaeva OV, Johnson MP, Kedishvili NY (2008) Kinetic analysis of human enzyme RDH10 defines the characteristics of a physiologically relevant retinol dehydrogenase. J Biol Chem 283:20299–20308. doi:10.1074/jbc.M800019200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Horiguchi Y, Araki M, Motojima K (2008) Identification and characterization of the ER/lipid droplet-targeting sequence in 17β-hydroxysteroid dehydrogenase type 11. Arch Biochem Biophys 479:121–130. doi:10.1016/j.abb.2008.08.020

    Article  CAS  PubMed  Google Scholar 

  11. Lukacik P, Kavanagh KL, Oppermann U (2006) Structure and function of human 17β-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 248:61–71. doi:10.1016/j.mce.2005.12.007

    Article  CAS  PubMed  Google Scholar 

  12. Brereton P, Suzuki T, Sasano H et al (2001) Pan1b (17βHSD11)-enzymatic activity and distribution in the lung. Mol Cell Endocrinol 171:111–117. doi:10.1016/S0303-7207(00)00417-2

    Article  CAS  PubMed  Google Scholar 

  13. Yokoi Y, Horiguchi Y, Araki M, Motojima K (2007) Regulated expression by PPARalpha and unique localization of 17beta-hydroxysteroid dehydrogenase type 11 protein in mouse intestine and liver. FEBS J 274:4837–4847. doi:10.1111/j.1742-4658.2007.06005.x

    Article  CAS  PubMed  Google Scholar 

  14. Steckelbroeck S, Watzka M, Reissinger A et al (2003) Characterisation of estrogenic 17β-hydroxysteroid dehydrogenase (17β-HSD) activity in the human brain. J Steroid Biochem Mol Biol 86:79–92. doi:10.1016/S0960-0760(03)00251-6

    Article  CAS  PubMed  Google Scholar 

  15. Keller B, Grote K, Adamski J (2006) In silico Northern blot, an automated method to determine expression patterns from EST databases, reveals tissue specificity of murine 17beta-hydroxysteroid dehydrogenase type 11. Mol Cell Endocrinol 248:242–245. doi:10.1016/j.mce.2005.11.033

    Article  CAS  PubMed  Google Scholar 

  16. Rotinen M, Villar J, Celay J et al (2011) Transcriptional regulation of type 11 17β-hydroxysteroid dehydrogenase expression in prostate cancer cells. Mol Cell Endocrinol 339:45–53. doi:10.1016/j.mce.2011.03.015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Rotinen M, Villar J, Celay J, Encío I (2010) Type 10 17β-hydroxysteroid dehydrogenase expression is regulated by C/EBPβ in HepG2 cells. J Steroid Biochem Mol Biol 122:164–171. doi:10.1016/j.jsbmb.2010.07.003

    Article  CAS  PubMed  Google Scholar 

  18. Štambergová H, Škarydová L, Dunford JE, Wsól V (2014) Biochemical properties of human dehydrogenase/reductase (SDR family) member 7. Chem Biol Interact 207:52–57. doi:10.1016/j.cbi.2013.11.003

    Article  PubMed  Google Scholar 

  19. Hirokawa T, Boon-Chieng S, Mitaku S (1998) SOSUI: classification and secondary structure prediction system for membrane proteins. Bioinformatics 14:378–379. doi:10.1093/bioinformatics/14.4.378

    Article  CAS  PubMed  Google Scholar 

  20. Tusnády GE, Simon I (2001) The HMMTOP transmembrane topology prediction server. Bioinformatics 17:849–850

    Article  PubMed  Google Scholar 

  21. Hofmann K, Stoffel W (1993) TMbase—a database of membrane spanning protein segments. Biol Chem Hoppe- Seyler 374:166

    Google Scholar 

  22. Bernsel A, Viklund H, Hennerdal A, Elofsson A (2009) TOPCONS: consensus prediction of membrane protein topology. Nucleic Acids Res 37:W465–W468. doi:10.1093/nar/gkp363

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Buchan DWA, Minneci F, Nugent TCO et al (2013) Scalable web services for the PSIPRED Protein Analysis Workbench. Nucleic Acids Res 41:W349–W357. doi:10.1093/nar/gkt381

    Article  PubMed Central  PubMed  Google Scholar 

  24. Tsaousis GN, Bagos PG, Hamodrakas SJ (2014) HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. Biochim Biophys Acta Proteins Proteomics 1844:316–322. doi:10.1016/j.bbapap.2013.11.001

    Article  CAS  Google Scholar 

  25. Lapshina EA, Belyaeva OV, Chumakova OV, Kedishvili NY (2003) Differential recognition of the free versus bound retinol by human microsomal retinol/sterol dehydrogenases: characterization of the holo-CRBP dehydrogenase activity of RoDH-4. Biochemistry 42:776–784. doi:10.1021/bi026836r

    Article  CAS  PubMed  Google Scholar 

  26. Lundová T, Zemanová L, Malčeková B et al (2015) Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3). Chem Biol Interact 234:178–187. doi:10.1016/j.cbi.2014.10.018

    Article  PubMed  Google Scholar 

  27. Belyaeva OV, Stetsenko AV, Nelson P, Kedishvili NY (2003) Properties of short-chain dehydrogenase/reductase RalR1: characterization of purified enzyme, its orientation in the microsomal membrane, and distribution in human tissues and cell lines. Biochemistry 42:14838–14845. doi:10.1021/bi035288u

    Article  CAS  PubMed  Google Scholar 

  28. Gallego O, Belyaeva OV, Porté S et al (2006) Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases and aldo-keto reductases with retinoids. Biochem J 399:101–109. doi:10.1042/BJ20051988

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Wang J, Bongianni JK, Napoli JL (2001) The N-terminus of retinol dehydrogenase type 1 signals cytosolic orientation in the microsomal membrane. Biochemistry 40:12533–12540. doi:10.1021/bi011396+

    Article  CAS  PubMed  Google Scholar 

  30. Gry M, Rimini R, Strömberg S et al (2009) Correlations between RNA and protein expression profiles in 23 human cell lines. BMC Genom. doi:10.1186/1471-2164-10-365

    Google Scholar 

  31. Takahashi Y, Moiseyev G, Farjo K, Ma J-X (2009) Characterization of key residues and membrane association domains in retinol dehydrogenase 10. Biochem J 419:113–122. doi:10.1042/BJ20080812

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Labrie F, Luu-The V, Lin S et al (1997) The key role of 17β-hydroxysteroid dehydrogenases in sex steroid biology. Steroids 62:148–158

    Article  CAS  PubMed  Google Scholar 

  33. Haeseleer F, Palczewski K (2000) Short-chain dehydrogenase/reductase in retina. Methods Enzymol 316:372–383

    Article  CAS  PubMed  Google Scholar 

  34. Chetyrkin SV, Hu J, Gough WH et al (2001) Further characterization of human microsomal 3alpha-hydroxysteroid dehydrogenase. Arch Biochem Biophys 386:1–10. doi:10.1006/abbi.2000.2203

    Article  CAS  PubMed  Google Scholar 

  35. Motojima K, Hirai T (2006) Peroxisome proliferator-activated receptor alpha plays a vital role in inducing a detoxification system against plant compounds with crosstalk with other xenobiotic nuclear receptors. FEBS J 273:292–300. doi:10.1111/j.1742-4658.2005.05060.x

    Article  CAS  PubMed  Google Scholar 

  36. Motojima K (2004) 17β-hydroxysteroid dehydrogenase type 11 is a major peroxisome proliferator-activated receptor alpha-regulated gene in mouse intestine. Eur J Biochem 271:4141–4146. doi:10.1111/j.1432-1033.2004.04352.x

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This project was supported by the Grant Agency of Charles University (Grant No. 677012/C/2012), the European Social Fund and the state budget of the Czech Republic (TEAB, project no. CZ.1.07/2.3.00/20.0235) and the Charles University project SVV 260 186. We would like to thank Prof. Udo Oppermann (SGC, University of Oxford, UK) for providing DHRS8 cDNA. We thank Daniel Sampey, MFA for his help with the English language editing.

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Authors and Affiliations

  1. Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic

    Tereza Lundová, Hana Štambergová, Lucie Zemanová, Markéta Svobodová, Jana Havránková & Vladimír Wsól

  2. Institute of Legal Medicine, Faculty of Medicine, Charles University and University Hospital in Hradec Králové, Sokolská 581, 500 05, Hradec Králové, Czech Republic

    Miroslav Šafr

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  1. Tereza Lundová
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Correspondence to Vladimír Wsól.

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Lundová, T., Štambergová, H., Zemanová, L. et al. Human dehydrogenase/reductase (SDR family) member 8 (DHRS8): a description and evaluation of its biochemical properties. Mol Cell Biochem 411, 35–42 (2016). https://doi.org/10.1007/s11010-015-2566-0

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  • DOI: https://doi.org/10.1007/s11010-015-2566-0

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