The other side of the Maillard reaction.
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. alpha-Crystallin, comprising alphaA- and alphaB-crystallin, is a major protein of the lens and it functions as a chaperone protein. We have found that upon reaction with MGO, human alphaA-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 alphaA-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.
Nagaraj
Ram H
RH
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. ram.nagaraj@case.edu
Biswas
Ashis
A
Miller
Antonia
A
Oya-Ito
Tomoko
T
Bhat
Manjunatha
M
D000375:Aging / Q000502:physiology; D002386:Cataract / Q000503:physiopathology*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D007908:Lens, Crystalline / Q000254:growth & development; D015416:Maillard Reaction; D011765:Pyruvaldehyde / Q000737:chemistry
D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde