Purchase this article with an account.
Prajitha Thampi, Azeem Hassan, Jean B. Smith, Edathara C. Abraham; Enhanced C-Terminal Truncation of αA- and αB-Crystallins in Diabetic Lenses. Invest. Ophthalmol. Vis. Sci. 2002;43(10):3265-3272.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. To investigate the influence of diabetes on the cleavage of C-terminal amino acid residues of αA- and αB-crystallins in human and rat lenses.
methods. The human lenses were diabetic or age-matched control lenses from donors 57, 59, 69, and 72 years of age. Lenses were also obtained from streptozotocin-induced diabetic rats. Individual lens crystallins in water-soluble fractions were separated by gel-permeation chromatography. The high (αH)- and low (αL)-molecular-weight fractions were analyzed by electrospray ionization mass spectrometry.
results. A typical mass spectrum of αA-crystallin from human lenses showed intact unmodified αA-crystallin, truncated αA1-172, and monophosphorylated αA-crystallin. Diabetic lenses showed nearly twofold higher levels of αA1-172 than did the control lenses. Also, the αH fraction consistently showed significantly higher levels of αA1-172 than the αL fraction. Human αB-crystallin showed no evidence of C-terminal truncation. Rat αA-crystallin had five C-terminal–truncated components, most of which showed substantial increases in diabetes. Truncated αA1-162 appeared only in the diabetic rat lenses, suggesting specific activation of m-calpain in diabetes. αB-crystallin had only one C-terminal–truncated component, αB1-170, which also showed increased levels in diabetes.
conclusions. These data suggest that diabetic stress causes either enzymatic or nonenzymatic cleavage of peptide bonds between specific C-terminal amino acid residues. Such truncated α-crystallins appear to contribute to an increased level of the αH fraction generally present in diabetic lenses. Loss of αA-crystallin chaperone activity seems to be related to truncation of the C-terminal amino acid residues.
This PDF is available to Subscribers Only