Alpha-crystallin-mediated protection of lens cells against heat and oxidative stress-induced cell death

Biochim Biophys Acta. 2014 Feb;1843(2):309-15. doi: 10.1016/j.bbamcr.2013.11.010. Epub 2013 Nov 22.


In addition to their key role as structural lens proteins, α-crystallins also appear to confer protection against many eye diseases, including cataract, retinitis pigmentosa, and macular degeneration. Exogenous recombinant α-crystallin proteins were examined for their ability to prevent cell death induced by heat or oxidative stress in a human lens epithelial cell line (HLE-B3). Wild type αA- or αB-crystallin (WT-αA and WT-αB) and αA- or αB-crystallins, modified by the addition of a cell penetration peptide (CPP) designed to enhance the uptake of proteins into cells (gC-αB, TAT-αB, gC-αA), were produced by recombinant methods. In vitro chaperone-like assays were used to assay the ability of α-crystallins to protect client proteins from chemical or heat induced aggregation. In vivo viability assays were performed in HLE-B3 to determine whether pre-treatment with α-crystallins reduced death after exposure to oxidative or heat stress. Most of the five recombinant α-crystallin proteins tested conferred some in vitro protection from protein aggregation, with the greatest effect seen with WT-αB and gC-αB. All α-crystallins displayed significant protection to oxidative stress induced cell death, while only the αB-crystallins reduced cell death induced by thermal stress. Our findings indicate that the addition of the gC tag enhanced the protective effect of αB-crystallin against oxidative but not thermally-induced cell death. In conclusion, modifications that increase the uptake of α-crystallin proteins into cells, without destroying their chaperone-like activity and anti-apoptotic functions, create the potential to use these proteins therapeutically.

Keywords: Alpha crystallin; Apoptosis; Lens; Small heat shock protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aldehyde Reductase / metabolism
  • Cell Death / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cell-Penetrating Peptides / pharmacology
  • Crystallins / metabolism
  • Crystallins / pharmacology*
  • Cytoprotection / drug effects*
  • Hot Temperature*
  • Humans
  • Lens, Crystalline / pathology*
  • Oxidative Stress / drug effects*
  • Protein Structure, Quaternary
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / toxicity
  • alpha-Crystallin B Chain / pharmacology*


  • CRYAA protein, human
  • CRYAB protein, human
  • Cell-Penetrating Peptides
  • Crystallins
  • Recombinant Proteins
  • alpha-Crystallin B Chain
  • Aldehyde Reductase