| Retinol dehydrogenase 12 detoxifies 4-hydroxynonenal in photoreceptor cells. | |
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MedLine Citation:
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PMID: 19686838 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Lea D Marchette; Debra A Thompson; Marina Kravtsova; Thierry N Ngansop; Md Nawajes A Mandal; Anne Kasus-Jacobi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-08-14 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 48 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-03 Completed Date: 2010-04-26 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 16-25 Citation Subset: IM |
Copyright Information:
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Copyright 2009. Published by Elsevier Inc. |
Affiliation:
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Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Oxidoreductases
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genetics,
metabolism* Aldehydes / metabolism*, pharmacology Animals Apoptosis / drug effects Cell Line Dose-Response Relationship, Drug Humans Immunohistochemistry Light Lipid Peroxidation Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mutation Phenotype Photoreceptor Cells / drug effects, metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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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 |
| Chemical | |
Reg. No./Substance:
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0/Aldehydes; 29343-52-0/4-hydroxy-2-nonenal; EC 1.1.-/Alcohol Oxidoreductases; EC 1.1.1.105/RDH12 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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