Vitamin C Mediates Chemical Aging of Lens Crystallins by the Maillard Reaction in a Humanized Mouse Model

Senile cataracts are associated with progressive oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. We hypothesized that the Maillard reaction, which leads browning and aroma development during the baking of foods, would occur between the lens pro...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (45), p.16912-16917
Main Authors: Fan, Xingjun, Reneker, Lixing W., Obrenovich, Mark E., Strauch, Christopher, Cheng, Rongzhu, Jarvis, Simon M., Ortwerth, Beryl J., Monnier, Vincent M.
Format: Article
Language:English
Subjects:
Aging
Animals
Ascorbic Acid - metabolism
Ascorbic Acid - toxicity
Base Sequence
Biological Sciences
Cataract - etiology
Cataract - metabolism
Cataracts
Crystallins
Crystallins - drug effects
Crystallins - metabolism
Dehydroascorbic Acid - metabolism
DNA Primers - genetics
Fluorescence
Human aging
Humans
Lens, Crystalline - drug effects
Lens, Crystalline - metabolism
Maillard Reaction
Mice
Mice, Transgenic
Organic Anion Transporters, Sodium-Dependent - genetics
Organic Anion Transporters, Sodium-Dependent - metabolism
Oxidation
Photographic lenses
Proteins
Reaction products
Reactive Oxygen Species - metabolism
Reactive Oxygen Species - toxicity
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Sodium-Coupled Vitamin C Transporters
Symporters - genetics
Symporters - metabolism
Transgenic animals
Vitamin C
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Summary:Senile cataracts are associated with progressive oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. We hypothesized that the Maillard reaction, which leads browning and aroma development during the baking of foods, would occur between the lens proteins and the highly reactive oxidation products of vitamin C. To test this hypothesis, we engineered a mouse that selectively overexpresses the human vitamin C transporter SVCT2 in the lens. Consequently, lenticular levels of vitamin C and its oxidation products were 5- to 15-fold elevated, resulting in a highly compressed aging process and accelerated formation of several protein-bound advanced Maillard reaction products identical with those of aging human lens proteins. These data strongly implicate vitamin C in lens crystallin aging and may serve as a model for protein aging in other tissues particularly rich in vitamin C, such as the hippocampal neurons and the adrenal gland. The hSVCT2 mouse is expected to facilitate the search for drugs that inhibit damage by vitamin C oxidation products.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0605101103