Open AccessVitamin C mediates chemical aging of lens crystallins by the Maillard reaction in a humanized mouse model
Author(s) -
Xingjun Fan,
Lixing W. Reneker,
Mark E. Obrenovich,
Christopher Strauch,
Rongzhu Cheng,
Simon M. Jarvis,
B.J. Ortwerth,
Vincent M. Monnier
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0605101103
Subject(s) - maillard reaction , crystallin , browning , biochemistry , cataracts , chemistry , vitamin , vitamin c , lens (geology) , biology , genetics , paleontology
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.