cDNA cloning and characterization of a cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase
- PMID: 9407098
- DOI: 10.1074/jbc.272.52.33125
cDNA cloning and characterization of a cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase
Abstract
We report a mouse cDNA that encodes a 317-amino acid short-chain dehydrogenase which recognizes as substrates 9-cis-retinol, 11-cis-retinol, 5alpha-androstan-3alpha,17beta-diol, and 5alpha-androstan-3alpha-ol-17-one. This cis-retinol/androgen dehydrogenase (CRAD) shares closest amino acid similarity with mouse retinol dehydrogenase isozymes types 1 and 2 (86 and 91%, respectively). Recombinant CRAD uses NAD+ as its preferred cofactor and exhibits cooperative kinetics for cis-retinoids, but Michaelis-Menten kinetics for 3alpha-hydroxysterols. Unlike recombinant retinol dehydrogenase isozymes, recombinant CRAD was inhibited by 4-methylpyrazole, was not stimulated by ethanol, and did not require phosphatidylcholine for optimal activity. CRAD mRNA was expressed intensely in kidney and liver, in contrast to retinol dehydrogenase isozymes, which show strong mRNA expression only in liver. CRAD mRNA expression was widespread (relative abundance): kidney (100) > liver (92) > small intestine (9) = heart (9) > retinal pigment epithelium and sclera (4.5) > brain (2) > retina and vitreous (1.6) > spleen (0.7) > testis (0.6) > lung (0.4). CRAD may catalyze the first step in an enzymatic pathway from 9-cis-retinol to generate the retinoid X receptor ligand 9-cis-retinoic acid and/or may regenerate dihydrotestosterone from its catabolite 5alpha-androstan-3alpha,17beta-diol. These data also illustrate the multifunctional nature of short-chain dehydrogenases and provide a potential mechanism for androgen-retinoid interactions.
Similar articles
-
17beta-Hydroxysteroid dehydrogenase type 9 and other short-chain dehydrogenases/reductases that catalyze retinoid, 17beta- and 3alpha-hydroxysteroid metabolism.Mol Cell Endocrinol. 2001 Jan 22;171(1-2):103-9. doi: 10.1016/s0303-7207(00)00392-0. Mol Cell Endocrinol. 2001. PMID: 11165018 Review.
-
Complementary deoxyribonucleic acid cloning and enzymatic characterization of a novel 17beta/3alpha-hydroxysteroid/retinoid short chain dehydrogenase/reductase.Endocrinology. 1999 Nov;140(11):5275-84. doi: 10.1210/endo.140.11.7137. Endocrinology. 1999. PMID: 10537158
-
cDNA cloning and characterization of a new human microsomal NAD+-dependent dehydrogenase that oxidizes all-trans-retinol and 3alpha-hydroxysteroids.J Biol Chem. 1998 Jul 31;273(31):19778-85. doi: 10.1074/jbc.273.31.19778. J Biol Chem. 1998. PMID: 9677409
-
cDNA cloning, tissue distribution, and substrate characteristics of a cis-Retinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme.J Biol Chem. 1998 Jul 10;273(28):17910-6. doi: 10.1074/jbc.273.28.17910. J Biol Chem. 1998. PMID: 9651397
-
Involvement of alcohol dehydrogenase, short-chain dehydrogenase/reductase, aldehyde dehydrogenase, and cytochrome P450 in the control of retinoid signaling by activation of retinoic acid synthesis.Biochemistry. 1996 Sep 24;35(38):12221-7. doi: 10.1021/bi961176+. Biochemistry. 1996. PMID: 8823154 Review.
Cited by
-
Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice.J Biol Chem. 2015 Nov 6;290(45):27239-27247. doi: 10.1074/jbc.M115.682096. Epub 2015 Sep 21. J Biol Chem. 2015. PMID: 26391396 Free PMC article.
-
Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times.Biochim Biophys Acta. 2015 Feb;1849(2):94-111. doi: 10.1016/j.bbagrm.2014.08.003. Epub 2014 Aug 15. Biochim Biophys Acta. 2015. PMID: 25134739 Free PMC article. Review.
-
Regulation of retinoid-mediated signaling involved in skin homeostasis by RAR and RXR agonists/antagonists in mouse skin.PLoS One. 2013 Apr 24;8(4):e62643. doi: 10.1371/journal.pone.0062643. Print 2013. PLoS One. 2013. PMID: 23638129 Free PMC article.
-
Cholestenoic Acid is an important elimination product of cholesterol in the retina: comparison of retinal cholesterol metabolism with that in the brain.Invest Ophthalmol Vis Sci. 2011 Feb 1;52(1):594-603. doi: 10.1167/iovs.10-6021. Print 2011 Jan. Invest Ophthalmol Vis Sci. 2011. PMID: 20881306 Free PMC article.
-
Delayed dark adaptation in 11-cis-retinol dehydrogenase-deficient mice: a role of RDH11 in visual processes in vivo.J Biol Chem. 2005 Mar 11;280(10):8694-704. doi: 10.1074/jbc.M413172200. Epub 2005 Jan 4. J Biol Chem. 2005. PMID: 15634683 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases