Vitamin C-mediated Maillard reaction in the lens probed in a transgenic-mouse model.
Aging human lens crystallins are progressively modified by yellow glycation, oxidation, and cross-linked carbonyl compounds that have deleterious properties on protein structure and stability. In order to test the hypothesis that some of these compounds originate from oxidized vitamin C, we have overexpressed the human vitamin C transporter 2 (hSCVT2) in the mouse lens. We find that levels of ascorbic and dehydroascorbic acid are highly elevated compared to the wild type and that the lenses have accumulated yellow color and advanced Maillard reaction products identical with those of the human lens. Treatment of the mice with nucleophilic inhibitors can slow down the process, opening new avenues for the pharmacological prevention of senile cataractogenesis.
Fan
Xingjun
X
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Monnier
Vincent M
VM
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D003683:Dehydroascorbic Acid / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D015416:Maillard Reaction; D051379:Mice; D008822:Mice, Transgenic; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics
D017127:Glycation End Products, Advanced; D029363:Organic Anion Transporters, Sodium-Dependent; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid