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 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.
Fan
Xingjun
X
Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106-7288, USA.
Reneker
Lixing W
LW
Obrenovich
Mark E
ME
Strauch
Christopher
C
Cheng
Rongzhu
R
Jarvis
Simon M
SM
Ortwerth
Beryl J
BJ
Monnier
Vincent M
VM
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism* / Q000633:toxicity*; D001483:Base Sequence; D002386:Cataract / Q000209:etiology / Q000378:metabolism; D003459:Crystallins / Q000187:drug effects* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D003683:Dehydroascorbic Acid / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism*; D015416:Maillard Reaction; D051379:Mice; D008822:Mice, Transgenic; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics / Q000378:metabolism
D003459:Crystallins; D017931:DNA Primers; D029363:Organic Anion Transporters, Sodium-Dependent; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C555163:SLC23A2 protein, human; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid