Multiple and Additive Functions of ALDH3A1 and ALDH1A1
Mice, Knockout
0301 basic medicine
Aging
Proteasome Endopeptidase Complex
Ultraviolet Rays
Retinal Dehydrogenase
Aldehyde Dehydrogenase
Glutathione
Aldehyde Dehydrogenase 1 Family
Cataract
Cornea
Mice
Oxidative Stress
03 medical and health sciences
Phenotype
Lens, Crystalline
Animals
Eye Proteins
Oxidation-Reduction
DOI:
10.1074/jbc.m702076200
Publication Date:
2007-06-14T06:34:59Z
AUTHORS (11)
ABSTRACT
ALDH3A1 (aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable in the lens, and ALDH1A1 is present at lower (catalytic) levels in the cornea and lens. To test the hypothesis that ALDH3A1 and ALDH1A1 protect the anterior segment of the eye against environmentally induced oxidative damage, Aldh1a1(-/-)/Aldh3a1(-/-) double knock-out and Aldh1a1(-/-) and Aldh3a1(-/-) single knock-out mice were evaluated for biochemical changes and cataract formation (lens opacification). The Aldh1a1/Aldh3a1- and Aldh3a1-null mice develop cataracts in the anterior and posterior subcapsular regions as well as punctate opacities in the cortex by 1 month of age. The Aldh1a1-null mice also develop cataracts later in life (6-9 months of age). One- to three-month-old Aldh-null mice exposed to UVB exhibited accelerated anterior lens subcapsular opacification, which was more pronounced in Aldh3a1(-/-) and Aldh3a1(-/-)/Aldh1a1(-/-) mice compared with Aldh1a1(-/-) and wild type animals. Cataract formation was associated with decreased proteasomal activity, increased protein oxidation, increased GSH levels, and increased levels of 4-hydroxy-2-nonenal- and malondialdehyde-protein adducts. In conclusion, these findings support the hypothesis that corneal ALDH3A1 and lens ALDH1A1 protect the eye against cataract formation via nonenzymatic (light filtering) and enzymatic (detoxification) functions.
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