Oxidative stress increases production of beta-amyloid precursor protein and beta-amyloid (Abeta) in mammalian lenses, and Abeta has toxic effects on lens epithelial cells

J Biol Chem. 1996 Apr 26;271(17):10169-74. doi: 10.1074/jbc.271.17.10169.


Many amyloid diseases are characterized by protein aggregations linked to oxidative stress. Such diseases including those of the brain, muscle, and blood vessels exhibit plaques containing beta-amyloid (Abeta). Here we demonstrate that Alzheimer's precursor protein (betaAPP) and A beta are present at low levels in normal lenses and increase in intact cultured monkey lenses treated with H2O2 or UV radiation (known cataractogenic agents), and with phorbol 12-myristate 13-acetate. AP-1 factor binding, shown by others to up-regulate betaAPP expression, increased in the monkey lenses treated with H2O2, UV radiation, or phorbol 12-myristate 13-acetate and paralleled the increase in betaAPP expression. Rat lenses exposed to oxidative stress showed increased betaAPP in the anterior epithelium and cortex. Incubation of cultured rabbit lens N/N1003A epithelial cells with Abeta induced inclusions and vacuoles and was cytotoxic. Abeta cross-reacting protein was readily detected in the cortex of a cataractous human lens. Our data show that betaAPP and Abeta increase in mammalian lenses as part of a response to H2O2 or UV radiation and suggest that they may contribute to the mechanism by which oxidative damage leads to lens opacification.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Epithelial Cells
  • Gene Expression
  • Immunohistochemistry
  • Lens, Crystalline / cytology
  • Lens, Crystalline / metabolism*
  • Macaca mulatta
  • Organ Culture Techniques
  • Oxidation-Reduction
  • Oxidative Stress*
  • Peptide Fragments
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / metabolism
  • Transcription Factor AP-1 / metabolism
  • Ultraviolet Rays


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • RNA, Messenger
  • Transcription Factor AP-1