Enhanced C-terminal truncation of alphaA- and alphaB-crystallins in diabetic lenses

Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3265-72.


Purpose: To investigate the influence of diabetes on the cleavage of C-terminal amino acid residues of alphaA- and alphaB-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 (alphaH)- and low (alphaL)-molecular-weight fractions were analyzed by electrospray ionization mass spectrometry.

Results: A typical mass spectrum of alphaA-crystallin from human lenses showed intact unmodified alphaA-crystallin, truncated alphaA(1-172), and monophosphorylated alphaA-crystallin. Diabetic lenses showed nearly twofold higher levels of alphaA(1-172) than did the control lenses. Also, the alphaH fraction consistently showed significantly higher levels of alphaA(1-172) than the alphaL fraction. Human alphaB-crystallin showed no evidence of C-terminal truncation. Rat alphaA-crystallin had five C-terminal-truncated components, most of which showed substantial increases in diabetes. Truncated alphaA(1-162) appeared only in the diabetic rat lenses, suggesting specific activation of m-calpain in diabetes. alphaB-crystallin had only one C-terminal-truncated component, alphaB(1-170), 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 alpha-crystallins appear to contribute to an increased level of the alphaH fraction generally present in diabetic lenses. Loss of alphaA-crystallin chaperone activity seems to be related to truncation of the C-terminal amino acid residues.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Animals
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus, Experimental / metabolism*
  • Humans
  • Lens, Crystalline / metabolism*
  • Middle Aged
  • Peptide Fragments / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Spectrometry, Mass, Electrospray Ionization
  • alpha-Crystallins / metabolism*


  • Peptide Fragments
  • alpha-Crystallins