May 2004
Volume 45, Issue 13
ARVO Annual Meeting Abstract  |   May 2004
Enhanced degradation and altered ATP binding of methylglyoxal modified a–crystallin
Author Affiliations & Notes
  • S.K. Madala
    Biochemistry, National Inst of Nutrition, Hyderabad, India
  • P.Y. Reddy
    Biochemistry, National Inst of Nutrition, Hyderabad, India
  • M. Saraswat
    Biochemistry, National Inst of Nutrition, Hyderabad, India
  • G.B. Reddy
    Biochemistry, National Inst of Nutrition, Hyderabad, India
  • Footnotes
    Commercial Relationships  S.K. Madala, None; P.Y. Reddy, None; M. Saraswat, None; G.B. Reddy, None.
  • Footnotes
    Support  Counsil of Scientific and Industrial Research, INDIA
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3975. doi:
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      S.K. Madala, P.Y. Reddy, M. Saraswat, G.B. Reddy; Enhanced degradation and altered ATP binding of methylglyoxal modified a–crystallin . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3975.

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

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Abstract: : Purpose: To study ATP binding, stability and degradation of methylglyoxal modified α–crystallin with respect to its chaperone–like function. Background: Methylglyoxal (MGO), a potent glycating agent, forms advanced glycation end products (AGEs) with proteins. Several diabetic complications including cataract are thought to be result of accumulation of these protein–AGEs. α–Crystallin, molecular chaperone of the eye lens plays an important role in maintaining the transparency by preventing the inactivation/ aggregation of several enzymes/proteins in addition to its structural role. Binding of ATP to α–crystallin has been shown to enhance the chaperone–like function and protection against proteolytic digestion. Being a long–lived protein and rich in basic amino acids, α–crystallin is more susceptible to non–enzymatic browning by MGO. It is of significant importance to investigate the effect of these modifications on α–crystallin structure and function. Methods & Results: Proteolytic digestion using trypsin and chymotrypsin showed that MGO modified α–crystallin is more susceptible to degradation compared to native α–crystallin. ATP protected native α–crystallin against proteolytic digestion but not that of MGO–modified α–crystallin. Further, ATP binding studied by intrinsic tryptophan fluorescence quenching showed decreased ATP binding upon MGO modification of α–crystallin. Differential scanning calorimetric data indicate that modification of α–crystallin by MGO leads to decreased stability in a concentration dependent manner. However, contrasting results were obtained for chaperone–like activity of MGO–modified α–crystallin: enhanced chaperone–like activity was observed in preventing the aggregation of other proteins, but showed decreased ability in protecting the enzymes against inactivation by various treatments. Conclusions: These findings indicate that MGO–modification of α–crystallin leads to enhanced degradation, decreased stability and altered ATP binding. These results suggest that MGO–induced molecular changes to α–crystallin could be detrimental to lens transparency, despite increased chaperone–like activity in aggregation assays.

Keywords: cataract • protein modifications–post translational • proteolysis 

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