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a Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA b Present address: Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA c Present address: Monash University, Alfred Medical Research and Education Precinct, Victoria, Australia d Present address: Department of Medical Proteomics, Kyoto Prefectural University of Medicine, Kyoto, Japan e Department of Anesthesiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
Key Words: methylglyoxal •  -crystallin • chaperone function • argpyrimidine • hydroimidazolone
Address for correspondence: Ram H. Nagaraj, Ph.D., Department of Ophthalmology and Visual Sciences, 2085 Adelbert Road, Room 311, Case Western Reserve University, Cleveland, OH 44106. Voice: 216-368-2089; fax: 216-368-0743. ram.nagaraj{at}case.edu
The Maillard reaction plays an important role in eye lens aging and cataract formation. Methylglyoxal (MGO) is a metabolic dicarbonyl compound present in the lens. It reacts with arginine residues in lens proteins to form advanced glycation end products (AGEs), such as hydroimidazolones and argpyrimidine.
-Crystallin, comprising A- and B-crystallin, is a major protein of the lens and it functions as a chaperone protein. We have found that upon reaction with MGO, human A-crystallin becomes a more effective chaperone. Modification of specific arginine residues to AGEs appears to be the reason. Mutation of these arginine residues to alanine mirrors the effect of MGO, suggesting neutralization of the positive charge on arginine residues as a cause for improved chaperone function. Reaction with MGO also blocks the loss of the chaperone function of A-crystallin caused by nonenzymatic glycation by ascorbate and ribose. These findings suggest that low levels of MGO might help the lens remain transparent during aging.
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