Document Detail

Retinol dehydrogenase 12 detoxifies 4-hydroxynonenal in photoreceptor cells.
MedLine Citation:
PMID:  19686838     Owner:  NLM     Status:  MEDLINE    
Mutations of the photoreceptor retinol dehydrogenase 12 (RDH12) gene cause the early onset retinal dystrophy Leber congenital amaurosis (LCA) by mechanisms not completely resolved. Determining the physiological role of RDH12 in photoreceptors is the focus of this study. Previous studies showed that RDH12, and the closely related retinol dehydrogenase RDH11, can enzymatically reduce toxic lipid peroxidation products such as 4-hydroxynonenal (4-HNE), in vitro. To explore the significance of this activity, we investigated the ability of RDH11 and RDH12 to protect stably transfected HEK-293 cells against the toxicity of 4-HNE. Both enzymes protected against 4-HNE modification of proteins and 4-HNE-induced apoptosis in HEK-293 cells. In the retina, exposure to bright light induced lipid peroxidation, 4-HNE production, and 4-HNE modification of proteins in photoreceptor inner segments, where RDH11 and RDH12 are located. In mouse retina, RDH12-but not RDH11-protected against adduct formation, suggesting that 4-HNE is a physiological substrate of RDH12. RDH12-but not RDH11-also protected against light-induced apoptosis of photoreceptors. We conclude that in mouse retina RDH12 reduces 4-HNE to a nontoxic alcohol, protecting cellular macromolecules against oxidative modification and protecting photoreceptors from light-induced apoptosis. This activity is of particular significance to the understanding of the molecular mechanisms of RDH12-induced LCA.
Lea D Marchette; Debra A Thompson; Marina Kravtsova; Thierry N Ngansop; Md Nawajes A Mandal; Anne Kasus-Jacobi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-08-14
Journal Detail:
Title:  Free radical biology & medicine     Volume:  48     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-04-26     Revised Date:  2011-07-19    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16-25     Citation Subset:  IM    
Copyright Information:
Copyright 2009. Published by Elsevier Inc.
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
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MeSH Terms
Alcohol Oxidoreductases / genetics,  metabolism*
Aldehydes / metabolism*,  pharmacology
Apoptosis / drug effects
Cell Line
Dose-Response Relationship, Drug
Lipid Peroxidation
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Photoreceptor Cells / drug effects,  metabolism*,  pathology
Grant Support
P20 RR017703-086150/RR/NCRR NIH HHS; P20RR017703/RR/NCRR NIH HHS; P30EY012190/EY/NEI NIH HHS; R21 EY018907-01A1/EY/NEI NIH HHS; R21EY018907/EY/NEI NIH HHS
Reg. No./Substance:
0/Aldehydes; 29343-52-0/4-hydroxy-2-nonenal; EC 1.1.-/Alcohol Oxidoreductases; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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