Initial characterization of human DHRS1 (SDR19C1), a member of the short-chain dehydrogenase/reductase superfamily. Issue 185 (January 2019)

• Record Type: Journal Article
• Authors: Zemanová, Lucie; Navrátilová, Hana; Andrýs, Rudolf; Šperková, Kristýna; Andrejs, Jiří; Kozáková, Klára; Meier, Marc; Möller, Gabriele; Novotná, Eva; Šafr, Miroslav; Adamski, Jerzy; Wsól, Vladimír
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 185(2019)
• Page Start: 80
• Page End: 89
• Publication Date: 2019-01
• Subjects: 11β-HSD1 11β-hydroxysteroid dehydrogenase 1 -- A-dione 4-androstene-3, 17-dione -- AEBSF 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride -- AhR aryl hyrocarbone receptor -- BSA bovine serum albumin -- CAR constitutive androstane receptor -- CMC critical micellar concentration -- C12E8 octaethylene glycol monododecyl ether -- DHRS1 dehydrogenase/reductase (SDR family) member 1 -- DDM n-dodecyl-β-D-maltoside -- DTT dithiothreitol -- ER endoplasmic reticulum -- CHAPS 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate hydrate -- LD lipid droplet -- NADPH nicotine amide dinucleotide phosphate -- NNK 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) -- PGE1 prostaglandin E1 -- PMSF phenylmethylsulfonyl fluoride -- RDH10 retinol dehydrogenase 10 -- SDR short-chain dehydrogenase/reductase -- SFS structure and function summary; DHRS1 -- SDR19C1 -- SDR superfamily -- Steroid hormones -- Xenobiotics; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2018.07.013
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: DHRS1 is a monotopic membrane protein from the endoplasmic reticulum. DHRS1 is an NADPH-dependent reductase of steroid hormones and xenobiotics. DHRS1 expression patterns were determined at both the mRNA and the protein levels. Abstract: Many enzymes from the short-chain dehydrogenase/reductase superfamily (SDR) have already been well characterized, particularly those that participate in crucial biochemical reactions in the human body ( e.g. 11β-hydroxysteroid dehydrogenase 1, 17β-hydroxysteroid dehydrogenase 1 or carbonyl reductase 1). Several other SDR enzymes are completely or almost completely uncharacterized, such as DHRS1 (also known as SDR19C1). Based on our in silico and experimental approaches, DHRS1 is described as a likely monotopic protein that interacts with the membrane of the endoplasmic reticulum. The highest expression level of DHRS1 protein was observed in human liver and adrenals. The recombinant form of DHRS1 was purified using the detergent n-dodecyl-β-D-maltoside, and DHRS1 was proven to be an NADPH-dependent reductase that is able to catalyse the in vitro reductive conversion of some steroids (estrone, androstene-3, 17-dione and cortisone), as well as other endogenous substances and xenobiotics. The expression pattern and enzyme activities fit to a role in steroid and/or xenobiotic metabolism; however, more research is needed to fully clarify the exact biological function of DHRS1.