| Aldh3a1 protects human corneal epithelial cells from ultraviolet- and 4-hydroxy-2-nonenal-induced oxidative damage. | |
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MedLine Citation:
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PMID: 12706498 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aldehyde dehydrogenase 3A1 (ALDH3A1) is one of the most abundant proteins found in corneal epithelial cells of mammalian species, with several postulated protective roles that include detoxification of peroxidic aldehydes, scavenging of free radicals, and direct absorption of ultraviolet (UV) radiation. In the present study, the protective role of ALDH3A1 against UV- and 4-hydroxy-2-nonenal- (4-HNE-) induced oxidative damage was studied. For this purpose, human ALDH3A1 was stably transfected in a human corneal epithelial cell line (HCE) lacking endogenous enzyme. Cells transfected with ALDH3A1 were more resistant to UV- and 4-HNE-induced cytotoxicity than mock-transfected cells. DNA fragmentation assays revealed that both treatments induced apoptosis in mock-transfected cells, but not in ALDH3A1-expressing cells. Apoptosis appeared to occur via caspase-3 activation and subsequent PARP cleavage. The Michaelis-Menten constant (K(m)) for 4-HNE was 54 microM in ALDH3A1-transfected cells; the addition of 100 microM 4-HNE increased NAD(P)H levels by 50% above that in mock-transfected cells. We also found that ALDH3A1 expression prevented 4-HNE-induced protein adduct formation. Taken together, these data suggest that ALDH3A1 is a regulatory element of the cellular defense system that protects corneal epithelium against UV- and 4-HNE-induced oxidative damage. |
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Authors:
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Aglaia Pappa; Chunhe Chen; Yiannis Koutalos; Alan J Townsend; Vasilis Vasiliou |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Free radical biology & medicine Volume: 34 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2003 May |
Date Detail:
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Created Date: 2003-04-22 Completed Date: 2004-07-28 Revised Date: 2007-11-14 |
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: 1178-89 Citation Subset: IM |
Affiliation:
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Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver 80262, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldehyde Dehydrogenase
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genetics,
metabolism* Aldehydes / pharmacology* Apoptosis / drug effects Caspase 3 Caspases / antagonists & inhibitors, metabolism Cell Line Cornea / drug effects*, metabolism, pathology, radiation effects* Enzyme Activation Epithelial Cells / drug effects*, enzymology, metabolism, radiation effects* Humans NADP / metabolism Oxidative Stress / drug effects* Poly(ADP-ribose) Polymerases / metabolism Transfection Ultraviolet Rays / adverse effects* |
| Grant Support | |
ID/Acronym/Agency:
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EY11351/EY/NEI NIH HHS; EY11490/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aldehydes; 29343-52-0/4-hydroxy-2-nonenal; 53-59-8/NADP; EC 1.2.1.3/ALDH3A1 protein, human; EC 1.2.1.3/Aldehyde Dehydrogenase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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