AGE

, Volume 33, Issue 3, pp 377–384

Advanced glycation end products in diabetic and non-diabetic human subjects suffering from cataract

Article

Abstract

Advanced glycation end products (AGEs) play a pivotal role in loss of lens transparency, i.e., cataract. AGEs formation occurs as a result of sequential glycation and oxidation reaction between reducing sugars and protein. AGEs production takes place throughout the normal aging process but its accumulation is found to be more rapid in diabetic patients. In this study, we quantified AGEs and N-(carboxyethyl) lysine (CEL) in human cataractous lenses from non-diabetic (n = 50) and diabetic patients (n = 50) using ELISA. We observed significantly higher (p < 0.001) levels of lens AGEs and CEL in diabetic patients with cataract as compared with their respective controls. The presence of AGEs and CEL was also determined by western blotting and immuno-histochemical analysis. Furthermore, isolated β-crystallin from cataractous lenses of non-diabetic and diabetic patients was incubated with different sugars to evaluate the extent of glycation in a time dependent manner. Our data indicated more pronounced glycation in patients suffering from diabetes as compared to non-diabetics subjects demonstrating the need to focus on developing normoglycemic approaches. Such studies may provide an insight in developing therapeutic strategies and may have clinical implications.

Keywords

AGEs Cataract Diabetes CEL Non-enzymatic glycation 

References

  1. Ahmed N, Furth AJ (1991) A microassay for protein glycation based on the periodate method. Anal Biochem 192:109–111. doi:10.1016/0003-2697(91)90193-W PubMedCrossRefGoogle Scholar
  2. Ahmed MU, Brinkmann Frye E, Degenhardt TP, Thorpe SR, Baynes JW (1997) N-(carboxyethyl) lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. Biochem J 324:565–570PubMedGoogle Scholar
  3. Brian G, Taylor H (2001) Cataract blindness: challenges for the 21st century. Bull WHO 79:249–256. doi:10.1590/S0042-96862001000300015 PubMedGoogle Scholar
  4. Duhaiman AS (1995) Glycation of human lens proteins from diabetic and (nondiabetic) senile cataract patients. Glycoconj J 12:618–621. doi:10.1007/BF00731255 PubMedCrossRefGoogle Scholar
  5. Dunn JA, Patrick JS, Thorpe SR, Baynes JW (1989) Oxidation of glycated proteins: age-dependent accumulation of N-(carboxymethyl) lysine in lens proteins. Biochemistry 28:9464–9468. doi:10.1021/bi00450a033 PubMedCrossRefGoogle Scholar
  6. Franke S, Dawczynski J, Strobel J, Niwa T, Stahl P, Stein G (2003) Increased levels of advanced glycation end products in human cataractous lenses. J Cataract Refract Surg 29:998–1004. doi:10.1016/S0886-3350(02)01841-2 PubMedCrossRefGoogle Scholar
  7. Groenen PJ, Merck KB, de Jong WW, Bloemendal H (1994) Structure and modifications of the junior chaperone alpha-crystallin. From lens transparency to molecular pathology. Eur J Biochem 225:1–19. doi:10.1111/j.1432-1033.1994.00001.x PubMedCrossRefGoogle Scholar
  8. Gul A, Rahman MA, Salim A, Simjee SU (2009) Advanced glycation end products in senile diabetic and nondiabetic patients with cataract. J Diab Comp 23:343–348. doi:10.1016/j.jdiacomp.2008.04.001 CrossRefGoogle Scholar
  9. Harding JJ (1981) Changes in lens proteins in cataract. In: Bloemendal H (ed) Molecular and cellular biology of the eye lens. Wiley, New York, pp 327–365Google Scholar
  10. Harding JJ (2002) Viewing molecular mechanisms of ageing through a lens. Ageing Res Rev 1:465–479. doi:10.1016/S1568-1637(02)00012-0 PubMedCrossRefGoogle Scholar
  11. Hashim Z, Ilyas A, Saleem A, Salim A, Zarina S (2009) Expression and activity of paraoxonase 1 in human cataractous lens tissue. Free Rad Biol Med 46:1089–1095. doi:10.1016/j.freeradbiomed.2009.01.012 PubMedCrossRefGoogle Scholar
  12. Hashimoto H, Arai K, Yoshida S, Chikuda M, Obara Y (1997) Pentosidine and autofluorescence in lenses of diabetic patients. Jpn J Ophthalmol 41:274–277. doi:10.1016/S0021-5155(97)00056-7 PubMedCrossRefGoogle Scholar
  13. Ivancic D, Mandic Z, Barac J, Kopic M (2005) Cataract surgery and post operative complication in diabetic patients. Coll Antropol 29:55–58. doi:10.1016/collantropol.2005 PubMedGoogle Scholar
  14. Jadoon Z, Shah SP, Bourne R, Dineen B, Khan MA, Gilbert CE, Foster A, Khan MD (2007) Cataract prevalence, cataract surgical coverage and barriers to uptake of cataract surgical services in Pakistan: the Pakistan national blindness and visual impairment survey. Br J Ophthalmol 91:1269–1273. doi:10.1136/bjo.2006.106914 PubMedCrossRefGoogle Scholar
  15. Kokiwar PR, Gupta S, Durge PM (2007) Prevalence of diabetes in a rural area of central India. Int J Diab Dev Ctries 27:8–10. doi:10.4103/0973-3930.34750 CrossRefGoogle Scholar
  16. Kumar PA, Kumar MS, Reddy GB (2007) Effect of glycation on rat alpha-crystallin structure and chaperone-like function. Biochem J 408:251–258. doi:10.1042/BJ20070989 PubMedCrossRefGoogle Scholar
  17. Laemmli UK (1970) Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227:680–685. doi:10.1038/227680a0 PubMedCrossRefGoogle Scholar
  18. Monnier VM, Cerami A (1981) Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science 211:491–493. doi:10.1126/science.6779377 PubMedCrossRefGoogle Scholar
  19. Monnier VM, Stevens VJ, Cerami A (1979) Nonenzymatic glycosylation, sulfhydryl oxidation and aggregation of lens proteins in experimental sugar cataracts. J Exp Med 150:1098–1107. doi:10.1084/jem.150.5.1098 PubMedCrossRefGoogle Scholar
  20. Nagaraj RH, Monnier VM (1992) Isolation and characterization of a blue fluorophore from human eye lens crystallins: in vitro formation from Maillard reaction with ascorbate and ribose. Biochim Biophys Acta 1116:34–42. doi:10.1016/0304-4165(92)90125-E PubMedGoogle Scholar
  21. Nagaraj RH, Sady C (1996) The presence of a glucose-derived Maillard reaction product in the human lens. FEBS Lett 382:234–238. doi:10.1016/0014-5793(96)00142-1 PubMedCrossRefGoogle Scholar
  22. Nagaraj RH, Sell DR, Prabhakaram M, Ortwerth BJ, Monnier VM (1991) High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis. Proc Natl Acad Sci USA 88:10257–10261. doi:10.1073/pnas.88.22.10257 PubMedCrossRefGoogle Scholar
  23. Namiki M, Oka M, Otsuka M, Miyazawa T, Fujimoto K, Namiki K (1993) Weak Chemiluminescence at an early stage of Maillard reaction. J Agric Food Chem 41:1704–1709. doi:10.1021/jf00034a035 CrossRefGoogle Scholar
  24. Nathan DM (1993) Long-term complications of diabetes mellitus. N Engl J Med 328:1676–1685. doi:10.1056/NEJM199306103282306 PubMedCrossRefGoogle Scholar
  25. Peppa M, Uribarri J, Vlassara H (2003) Glucose, advanced glycation end products, and diabetes complications: What is new and what works. Clin Diab 21:186–187. doi:10.2337/diaclin.21.4.186 CrossRefGoogle Scholar
  26. Peppa M, Uribarri J, Vlassara H (2004) The role of advanced glycation end products in the development of atherosclerosis. Curr Diabetes Rep 4:31–36. doi:10.1007/s11892-004-0008-6 CrossRefGoogle Scholar
  27. Pokupec R, Kalauz M, Turk N, Turk Z (2003) Advanced glycation endproducts in human diabetic and non-diabetic cataractous lenses. Graefe Arch Clin Exp Ophthalmol 241:378–384. doi:10.1007/s00417-002-0616-2 CrossRefGoogle Scholar
  28. Pollreisz A, Schmidt-Erfurth U (2010) Diabetic cataract pathogenesis, epidemiology and treatment. J Ophthalmol. doi:10.1155/2010/608751 PubMedGoogle Scholar
  29. Rathur HM, Boulton AJ (2007) The diabetic foot. Clin Dermatol 25:109–120. doi:10.1016/j.clindermatol.2006.09.015 PubMedCrossRefGoogle Scholar
  30. Reed NA, Oh D-J, Czymmek KJ, Duncan MK (2001) An immunohistochemical method for the detection of proteins in the vertebrate lens. J Immunol Methods 253:243–252. doi:10.1016/S0022-1759(01)00374-X PubMedCrossRefGoogle Scholar
  31. Stitt AW (2005) The Maillard reaction in eye diseases. Ann NY Acad Sci 1043:582–597. doi:10.1196/annals.1338.066 PubMedCrossRefGoogle Scholar
  32. Swamy MS, Abraham EC (1991) Differential glycation of rat alpha, beta and gamma crystallins. Exp Eye Res 52:439–444. doi:10.1016/0014-4835(91)90040-L PubMedCrossRefGoogle Scholar
  33. Vinson JA (2006) Oxidative stress in cataracts. Pathophysiology 13:151–162. doi:10.1016/j.pathophys.2006.05.006 PubMedCrossRefGoogle Scholar
  34. Yamagishi S, Matsui T, Ueda S, Nakamura K, Imaizumi T (2007) Advanced glycation end products (AGEs) and cardiovascular disease (CVD) in diabetes. Cardiovasc Hematol Agents Med Chem 5:236–240. doi:10.2174/187152507781058681 PubMedCrossRefGoogle Scholar
  35. Zarina S, Zhao HR, Abraham EC (2000) Advanced glycation end products in human senile and diabetic cataractous lenses. Mol Cell Biochem 210:29–34. doi:10.1023/A:1007015416572 PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association, Media, PA, USA 2010

Authors and Affiliations

  1. 1.National Center for ProteomicsUniversity of KarachiKarachiPakistan

Personalised recommendations