Non-enzymic modification of lens proteins by glucose and fructose: effects of ibuprofen.
Cataract is the major cause of blindness worldwide. Non-enzymic modification of lens proteins leading to a disruption of their short range order is an important route to cataract formation. A reaction between lens proteins and a compound found in the lens indicates a potential role for that compound in cataract formation. The reactions of glucose and fructose with lens protein in vitro were investigated. Fructose bound to lens protein at pH 6.9 in a time-dependent fashion over a period of 20 days. The reactions of both glucose and fructose with lens proteins and bovine serum albumin led to the formation of coloured and fluorescent compounds. The formation of such compounds was greater with fructose than with glucose. The kinetics of the reactions of lens proteins and bovine serum albumin with fructose as measured by the formation of the above compounds were not identical. This point must be appreciated when attempting to extrapolate from results obtained with bovine serum albumin as to the reactions of lens proteins. The incubation of lens proteins with fructose led to an enhancement of protein aggregation. The implications of the reactions between lens proteins and fructose for the formation of cataract in diabetics are discussed. Ibuprofen intake is associated with protection against cataract. At relatively high concentrations (10-20 mM) ibuprofen decreased the binding of fructose to lens protein: this decrease was statistically significant at selected times (Student's t-test, P less than 0.05). The formation of fluorescent compounds in the presence of fructose was also decreased by ibuprofen.(ABSTRACT TRUNCATED AT 250 WORDS)
Raza
K
K
Nuffield Laboratory of Ophthalmology, University of Oxford, U.K.
Harding
J J
JJ
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000187:drug effects*; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology*; D008970:Molecular Weight; D011485:Protein Binding / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013997:Time Factors
D003459:Crystallins; D005632:Fructose; D005947:Glucose; D007052:Ibuprofen