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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F16%3A10326442" target="_blank" >RIV/00179906:_____/16:10326442 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11150/16:10326442 RIV/00216208:11160/16:10326442

Výsledek na webu

<a href="http://link.springer.com/article/10.1007/s11010-015-2566-0" target="_blank" >http://link.springer.com/article/10.1007/s11010-015-2566-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s11010-015-2566-0" target="_blank" >10.1007/s11010-015-2566-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 3 alpha-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 beta-estradiol and testosterone in vitro; apparent K-m and V-max values were 39.86 A mu M and 0.80 nmol x mg(-1) x min(-1) for beta-estradiol and 1207.29 A mu M and 3.45 nmol x mg(-1) x 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 3 alpha-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 beta-estradiol and testosterone in vitro; apparent K-m and V-max values were 39.86 A mu M and 0.80 nmol x mg(-1) x min(-1) for beta-estradiol and 1207.29 A mu M and 3.45 nmol x mg(-1) x 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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/EE2.3.20.0235" target="_blank" >EE2.3.20.0235: Vybudování výzkumného týmu experimentální a aplikované biofarmacie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular and Cellular Biochemistry

ISSN

0300-8177

e-ISSN

—

Svazek periodika

411

Číslo periodika v rámci svazku

1-2

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

35-42

Kód UT WoS článku

000369808600004

EID výsledku v databázi Scopus

2-s2.0-84957432356