May 2003
Volume 44, Issue 13
ARVO Annual Meeting Abstract  |   May 2003
Enhancement of Chaperone Function of Alpha-crystallin by Methylglyoxal
Author Affiliations & Notes
  • R.H. Nagaraj
    Ophthalmology, Case Western Res Univ, Cleveland, OH, United States
  • R. Kumar
    Ophthalmology, Case Western Res Univ, Cleveland, OH, United States
  • S. Mehta
    Ophthalmology, Case Western Res Univ, Cleveland, OH, United States
  • A.K. Padival
    Medicine, Case Western Res University/VA Medical Center, Cleveland, OH, United States
  • Footnotes
    Commercial Relationships  R.H. Nagaraj, None; R. Kumar, None; S. Mehta, None; A.K. Padival, None.
  • Footnotes
    Support  RO1EY-09912, P30EY-11373, PO1DK- 57733, RPB and Ohio Lions Research Foundation
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 2139. doi:
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      R.H. Nagaraj, R. Kumar, S. Mehta, A.K. Padival; Enhancement of Chaperone Function of Alpha-crystallin by Methylglyoxal . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2139.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose:The chaperone function of alpha-crystallin has been proposed as a mechanism that prevents protein aggregation and insolubilization during lens aging and cataractogenesis. Methylglyoxal is present in relatively large quantities in the human lens. The reaction of MG with lens proteins results in fluorophores formation and crosslinking of proteins. We have observed that a methylglyoxal-derived product, argpyrimidine is present in the alpha-crystallin fraction of human lenses. Here we studied the effect of chemical modification by methylglyoxal (MG) and other physiological carbohydrates on the chaperone function of alpha-crystallin. Methods: Human and bovine alpha-crystallin were incubated with sugars, ascorbate, methylglyoxal or glyoxal under physiological conditions. Alpha-A and alpha-B crystallins, and the peptides corresponding to chaperone regions of alpha-crystallin were also incubated with MG. Chaperone function was assessed using citrate synthase or insulin or alcohol dehydrogenase as the target protein. Results: We found that modification of alpha-crystallin by MG enhances its chaperone function. Sugars and ascorbate have no such effect and actually reduce the chaperone function. Chaperone assay after immunoprecipitation or with immunoaffinity-purified argpyrimidine-alpha-crystallin indicates that 50-60% of the increased chaperone function is due to argpyrimidine formation. Incubation of alpha-crystallin with DL-glyceraldehyde and arginine-modifying agents also enhance chaperone function, and that the increased chaperone activity depends upon the extent of arginine modification. MG similarly enhances chaperone function of another small heat shock protein, Hsp27. Binding studies with 1,1'-bis(4-anilino) naphthalene-5,5'-disulfonic acid indicate that MG treatment increases the hydrophobicity of alpha-crystallin. Conclusions: Our results show that posttranslational modification by a metabolic product can enhance the chaperone function of alpha-crystallin and suggest that such a modification may be a protective mechanism against deleterious protein modifications associated with aging.

Keywords: protein modifications-post translational • crystallins • chaperones 

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