Human dehydrogenase/reductase (SDR family) member 11 is a novel type of 17β-hydroxysteroid dehydrogenase

被引：26
作者：
Endo, Satoshi [1 ]
Miyagi, Namiki [1 ]
Matsunaga, Toshiyuki [1 ]
Hara, Akira [2 ]
Ikari, Akira [1 ]
机构：
[1] Gifu Pharmaceut Univ, Biochem Lab, Gifu 5011196, Japan
[2] Gifu Univ, Fac Engn, Gifu 5011193, Japan
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2016年 / 472卷 / 01期
关键词：
DHRS11; 17 beta-Hydroxysteroid dehydrogenase; 3 beta-Hydroxysteroid dehydrogenase; Dehydroepiandrosterone; Neurosteroid; Isolithocholic acid; SHORT-CHAIN DEHYDROGENASE/REDUCTASE; KETO REDUCTASE FAMILY; MAMMALIAN REDUCTASES; IDENTIFICATION; DEHYDROEPIANDROSTERONE; NOMENCLATURE; METABOLISM; ISOFORM; PATHWAY; ENZYMES;
D O I：
10.1016/j.bbrc.2016.01.190
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We report characterization of a member of the short-chain dehydrogenase/reductase superfamily encoded in a human gene, DHRS11. The recombinant protein (DHRS11) efficiently catalyzed the conversion of the 17-keto group of estrone, 4- and 5-androstenes and 5 alpha-androstanes into their 17 beta-hydroxyl metabolites with NADPH as a coenzyme. In contrast, it exhibited reductive 3 beta-hydroxysteroid dehydrogenase activity toward 5 beta-androstanes, 5 beta-pregnanes, 4-pregnenes and bile acids. Additionally, DHRS11 reduced alpha-dicarbonyls (such as diacetyl and methylglyoxal) and alicyclic ketones (such as 1-indanone and loxoprofen). The enzyme activity was inhibited in a mixed-type manner by flavonoids, and competitively by carbenoxolone, glycyrrhetinic acid, zearalenone, curcumin and flufenamic acid. The expression of DHRS11 mRNA was observed widely in human tissues, most abundantly in testis, small intestine, colon, kidney and cancer cell lines. Thus, DHRS11 represents a novel type of 17 beta-hydroxysteroid dehydrogenase with unique catalytic properties and tissue distribution. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码：231 / 236
页数：6
相关论文
共 32 条
[1]   Reductive 17β-hydroxysteroid dehydrogenases in the sulfatase pathway: Critical in the cell proliferation of breast cancer [J].
Aka, Juliette A. ;
Mazumdar, Mausumi ;
Lin, Sheng-Xiang .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2009, 301 (1-2) :183-190
[2]   Comparative enzymology of 11β-hydroxysteroid dehydrogenase type 1 from six species [J].
Arampatzis, S ;
Kadereit, B ;
Schuster, D ;
Balazs, Z ;
Schweizer, RAS ;
Frey, FJ ;
Langer, T ;
Odermatt, A .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2005, 35 (01) :89-101
[3]   What are the physiological estrogens? [J].
Baker, Michael E. .
STEROIDS, 2013, 78 (03) :337-340
[4]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[5]   The Secreted Protein Discovery Initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: A bioinformatics assessment [J].
Clark, HF ;
Gurney, AL ;
Abaya, E ;
Baker, K ;
Baldwin, D ;
Brush, J ;
Chen, J ;
Chow, B ;
Chui, C ;
Crowley, C ;
Currell, B ;
Deuel, B ;
Dowd, P ;
Eaton, D ;
Foster, J ;
Grimaldi, C ;
Gu, QM ;
Hass, PE ;
Heldens, S ;
Huang, A ;
Kim, HS ;
Klimowski, L ;
Jin, YS ;
Johnson, S ;
Lee, J ;
Lewis, L ;
Liao, DZ ;
Mark, M ;
Robbie, E ;
Sanchez, C ;
Schoenfeld, J ;
Seshagiri, S ;
Simmons, L ;
Singh, J ;
Smith, V ;
Stinson, J ;
Vagts, A ;
Vandlen, R ;
Watanabe, C ;
Wieand, D ;
Woods, K ;
Xie, MH ;
Yansura, D ;
Yi, S ;
Yu, GY ;
Yuan, J ;
Zhang, M ;
Zhang, ZM ;
Goddard, A ;
Wood, WI .
GENOME RESEARCH, 2003, 13 (10) :2265-2270
[6]   Dehydroepiandrosterone Sulphate: Action and Mechanism in the Brain [J].
Dong, Y. ;
Zheng, P. .
JOURNAL OF NEUROENDOCRINOLOGY, 2012, 24 (01) :215-224
[7]   Properties and tissue distribution of a novel aldo-keto reductase encoding in a rat gene (Akr1b10) [J].
Endo, Satoshi ;
Matsunaga, Toshiyuki ;
Kuragano, Tsukasa ;
Ohno, Satoshi ;
Kitade, Yukio ;
Tajima, Kazuo ;
El-Kabbani, Ossama ;
Hara, Akira .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2010, 503 (02) :230-237
[8]   Backdoor pathway for dihydrotestosterone biosynthesis: Implications for normal and abnormal human sex development [J].
Fukami, Maki ;
Homma, Keiko ;
Hasegawa, Tomonobu ;
Ogata, Tsutomu .
DEVELOPMENTAL DYNAMICS, 2013, 242 (04) :320-329
[9]   Pseudo-symmetry of C19-steroids, alternative binding orientations and multispecificity in human estrogenic 17β-hydroxysteroid dehydrogenase [J].
Gangloff, A ;
Shi, R ;
Nahoum, V ;
Lin, SX .
FASEB JOURNAL, 2002, 16 (14) :274-+
[10]   Curcumin derivatives inhibit testicular 17β-hydroxysteroid dehydrogenase 3 [J].
Hua, Guo-Xin ;
Liang, Guang ;
Chu, Yanhui ;
Li, Xiaokun ;
Lian, Qing-Quang ;
Lin, Han ;
He, Yi ;
Huang, Yadong ;
Hardy, Dianne O. ;
Ge, Ren-Shan .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (08) :2549-2551
1234