Abstract
A high glucose concentration in vivo or an increased glucose of glucose 6-phosphate concentration in vitro has been found to lead to the glycosylation of epsilon-amino groups of lysine residues in bovine and rat lens crystallins. In vitro, this glycosylation imparts an increased susceptibility of the crystallins to sulfhydryl oxidation. Disulfide crosslinks result in the formation of high molecular weight aggregates and an opalescence in the crystallin solutions. The addition of reducing agents prevents as well as reverses the formation of high molecular weight aggregates and the opalescence of the crystallins. These phenomena suggest a new interpretation of previous results on cataract formation and a new approach for development of drugs to prevent cataracts.
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- ANET E. F. 3-DEOXYGLYCOSULOSES (3-DEOXYGLYCOSONES) AND THE DEGRADATION OF CARBOHYDRATES. Adv Carbohydr Chem. 1964;19:181–218. doi: 10.1016/s0096-5332(08)60282-9. [DOI] [PubMed] [Google Scholar]
- Auricchio G., Testa M. Some biochemical differences between cortical (pale) and nuclear (brown) cataracts. Ophthalmologica. 1972;164(3):228–235. doi: 10.1159/000306755. [DOI] [PubMed] [Google Scholar]
- Barber G. W. Human cataractogenesis: a review. Exp Eye Res. 1973 Jun;16(2):85–94. doi: 10.1016/0014-4835(73)90303-5. [DOI] [PubMed] [Google Scholar]
- Beisswenger P. J., Spiro R. G. Studies on the human glomerular basement membrane. Composition, nature of the carbohydrate units and chemical changes in diabetes mellitus. Diabetes. 1973 Mar;22(3):180–193. doi: 10.2337/diab.22.3.180. [DOI] [PubMed] [Google Scholar]
- Bookchin R. M., Gallop P. M. Structure of hemoglobin AIc: nature of the N-terminal beta chain blocking group. Biochem Biophys Res Commun. 1968 Jul 11;32(1):86–93. doi: 10.1016/0006-291x(68)90430-0. [DOI] [PubMed] [Google Scholar]
- Bunn H. F., Haney D. N., Gabbay K. H., Gallop P. M. Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. Biochem Biophys Res Commun. 1975 Nov 3;67(1):103–109. doi: 10.1016/0006-291x(75)90289-2. [DOI] [PubMed] [Google Scholar]
- Flückiger R., Winterhalter K. H. In vitro synthesis of hemoglobin AIc. FEBS Lett. 1976 Dec 1;71(2):356–360. doi: 10.1016/0014-5793(76)80969-6. [DOI] [PubMed] [Google Scholar]
- Haney D. N., Bunn H. F. Glycosylation of hemoglobin in vitro: affinity labeling of hemoglobin by glucose-6-phosphate. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3534–3538. doi: 10.1073/pnas.73.10.3534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kinoshita J. H. Mechanisms initiating cataract formation. Proctor Lecture. Invest Ophthalmol. 1974 Oct;13(10):713–724. [PubMed] [Google Scholar]
- Koenig R. J., Blobstein S. H., Cerami A. Structure of carbohydrate of hemoglobin AIc. J Biol Chem. 1977 May 10;252(9):2992–2997. [PubMed] [Google Scholar]
- Koenig R. J., Cerami A. Synthesis of hemoglobin AIc in normal and diabetic mice: potential model of basement membrane thickening. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3687–3691. doi: 10.1073/pnas.72.9.3687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kramps H. A., Hoenders H. J., Wollensak J. Protein changes in the human lens during development of senile nuclear cataract. Biochim Biophys Acta. 1976 May 20;434(1):32–43. doi: 10.1016/0005-2795(76)90032-5. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Obazawa H., Merola L. O., Kinoshita J. H. The effects of xylose on the isolated lens. Invest Ophthalmol. 1974 Mar;13(3):204–209. [PubMed] [Google Scholar]
- Pirie A. Color and solubility of the proteins of human cataracts. Invest Ophthalmol. 1968 Dec;7(6):634–650. [PubMed] [Google Scholar]
- Rerup C. C. Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev. 1970 Dec;22(4):485–518. [PubMed] [Google Scholar]
- Reynolds T. M. Chemistry of nonenzymic browning. II. Adv Food Res. 1965;14:167–283. doi: 10.1016/s0065-2628(08)60149-4. [DOI] [PubMed] [Google Scholar]
- Spector A., Li L. K., Augusteyn R. C., Schneider A., Freund T. -Crystallin. The isolation and characterization of distinct macromolecular fractions. Biochem J. 1971 Sep;124(2):337–343. doi: 10.1042/bj1240337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spector A. The aging of alpha-crystallin: a review. Exp Eye Res. 1973 Jun;16(2):115–121. doi: 10.1016/0014-4835(73)90306-0. [DOI] [PubMed] [Google Scholar]
- Spector A., Zorn M. Studies upon the sulfhydryl groups of calf lens alpha-crystallins. J Biol Chem. 1967 Aug 25;242(16):3594–3600. [PubMed] [Google Scholar]
- Spiro R. G. Search for a biochemical basis of diabetic microangiopathy. Diabetologia. 1976 Mar;12(1):1–14. doi: 10.1007/BF01221959. [DOI] [PubMed] [Google Scholar]
- Stevens V. J., Vlassara H., Abati A., Cerami A. Nonenzymatic glycosylation of hemoglobin. J Biol Chem. 1977 May 10;252(9):2998–3002. [PubMed] [Google Scholar]
- Trivelli L. A., Ranney H. M., Lai H. T. Hemoglobin components in patients with diabetes mellitus. N Engl J Med. 1971 Feb 18;284(7):353–357. doi: 10.1056/NEJM197102182840703. [DOI] [PubMed] [Google Scholar]
- Truscott R. J., Augusteyn R. C. Changes in human lens proteins during nuclear cataract formation. Exp Eye Res. 1977 Feb;24(2):159–170. doi: 10.1016/0014-4835(77)90256-1. [DOI] [PubMed] [Google Scholar]
- Truscott R. J., Augusteyn R. C. The state of sulphydryl groups in normal and cataractous human lenses. Exp Eye Res. 1977 Aug;25(2):139–148. doi: 10.1016/0014-4835(77)90126-9. [DOI] [PubMed] [Google Scholar]
- Varma S. D., Mikuni I., Kinoshita J. H. Flavonoids as inhibitors of lens aldose reductase. Science. 1975 Jun 20;188(4194):1215–1216. doi: 10.1126/science.1145193. [DOI] [PubMed] [Google Scholar]