Age-related cleavages of crystallins in human lens cortical fiber cells generate a plethora of endogenous peptides and high molecular weight complexes

Shih-Ping Su, Xiaomin Song, Dylan Xavier, J. Andrew Aquilina

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Low molecular weight peptides derived from the breakdown of crystallins have been reported in adult human lenses. The proliferation of these LMW peptides coincides with the earliest stages of cataract formation, suggesting that the protein cleavages involved may contribute to the aggregation and insolubilization of crystallins. This study reports the identification of 238 endogenous LMW crystallin peptides from the cortical extracts of four human lenses representing young, middle and old-age human lenses. Analysis of the peptide terminal amino acids showed that Lys and Arg were situated at the C-terminus with significantly higher frequency compared to other residues, suggesting that trypsin-like proteolysis may be active in the lens cortical fiber cells. Selected reaction monitoring analysis of an endogenous αA-crystallin peptide (αA₅₇₋₆₅) showed that the concentration of this peptide in the human lens increased gradually to middle age, after which the rate of αA₅₇₋₆₅ formation escalated significantly. Using 2D gel electrophoresis/nanoLC-ESI-MS/MS, 12 protein complexes of 40-150 kDa consisting of multiple crystallin components were characterized from the water soluble cortical extracts of an adult human lens. The detection of these protein complexes suggested the possibility of crystallin cross-linking, with these complexes potentially acting to stabilize degraded crystallins by sequestration into water soluble complexes.
Original languageEnglish
Pages (from-to)1878-1886
Number of pages9
JournalProteins: Structure, Function and Bioinformatics
Volume83
Issue number10
DOIs
Publication statusPublished - Oct 2015

Keywords

  • lens aging
  • crystallin
  • endogenous peptides
  • 2D gel electrophoresis
  • nanoLC-ESI-MS/MS
  • trypsin-like cleavage
  • NanoLC-ESI-MS/MS
  • Crystallin
  • Lens aging
  • Endogenous peptides
  • Trypsin-like cleavage

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