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

Xingjun Fan, Lixing W. Reneker, Mark E. Obrenovich, Christopher Strauch, Rongzhu Cheng, Simon M. Jams, Beryl J. Ortwerth, Vincent M. Monnier

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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.

Original languageEnglish (US)
Pages (from-to)16912-16917
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number45
DOIs
Publication statusPublished - Nov 7 2006
Externally publishedYes

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Keywords

  • Advanced glycation end products
  • Ascorbic acid cataract
  • Diabetes
  • Oxidation

ASJC Scopus subject areas

  • General

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