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Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16912-7. Epub 2006 Oct 30.

Vitamin C mediates chemical aging of lens crystallins by the Maillard reaction in a humanized mouse model.

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1
Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106-7288, USA.

Abstract

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.

PMID:
17075057
PMCID:
PMC1636553
DOI:
10.1073/pnas.0605101103
[Indexed for MEDLINE]
Free PMC Article

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