Nagaraj Ram H, Biswas Ashis, Miller Antonia, Oya-Ito Tomoko, Bhat Manjunatha
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Ann N Y Acad Sci. 2008 Apr;1126:107-12. doi: 10.1196/annals.1433.045.
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.
美拉德反应在晶状体老化和白内障形成过程中起着重要作用。甲基乙二醛（MGO）是晶状体中存在的一种代谢性二羰基化合物。它与晶状体蛋白中的精氨酸残基反应，形成晚期糖基化终产物（AGEs），如氢化咪唑酮和精氨嘧啶。由αA-晶状体蛋白和αB-晶状体蛋白组成的α-晶状体蛋白是晶状体的主要蛋白质，具有伴侣蛋白的功能。我们发现，与MGO反应后，人αA-晶状体蛋白成为一种更有效的伴侣蛋白。特定精氨酸残基被修饰为AGEs似乎是其原因。将这些精氨酸残基突变为丙氨酸可模拟MGO的作用，这表明精氨酸残基正电荷的中和是伴侣功能改善的原因。与MGO反应还能阻止由抗坏血酸和核糖的非酶糖基化引起的αA-晶状体蛋白伴侣功能的丧失。这些发现表明，低水平的MGO可能有助于晶状体在老化过程中保持透明。
