May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
AG126 Protects ARPE–19 Cells From Oxidative Stress via a Mechanism Dependent on RNA Transcription
Author Affiliations & Notes
  • C.T. Schulteis
    Ophthalmology, Immusol Inc, San Diego, CA
  • K.L. Rhoades
    Ophthalmology, Immusol Inc, San Diego, CA
  • A. Klimova
    Ophthalmology, Immusol Inc, San Diego, CA
  • A.G. Gutierrez
    Ophthalmology, Immusol Inc, San Diego, CA
  • N.F. Paoni
    Ophthalmology, Immusol Inc, San Diego, CA
  • F. Wong–Staal
    Ophthalmology, Immusol Inc, San Diego, CA
  • Footnotes
    Commercial Relationships  C.T. Schulteis, Immusol, Inc. E; K.L. Rhoades, Immusol, Inc. E; A. Klimova, Immusol, Inc. E; A.G. Gutierrez, Immusol, Inc. E; N.F. Paoni, Immusol, Inc. E; F. Wong–Staal, Immusol, Inc. E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1630. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      C.T. Schulteis, K.L. Rhoades, A. Klimova, A.G. Gutierrez, N.F. Paoni, F. Wong–Staal; AG126 Protects ARPE–19 Cells From Oxidative Stress via a Mechanism Dependent on RNA Transcription . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1630.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Abstract: : Purpose: Oxidative stress has been implicated in retinal damage associated with both dry and exudative forms of age–related macular degeneration. In vitro experiments in ARPE–19 cells have suggested that apoptotic cell death in response to oxidative stress occurs via a ceramide–mediated signaling mechanism (Barak, et al., (2001) Inv. Ophthalmol. & Vis. Sci., 42, 247). Additional reports have demonstrated that cultured cells can be protected from oxidative stress by the tyrphostin, AG126 (Garg & Tang (2003) BMC Ophthalmology, 3, 5). It remains unclear, however, whether AG126 protection occurs via tyrosine kinase inhibition or through an alternate mechanism. In this study, AG126 protection of ARPE–19 cells from oxidative stress and ceramide–induced apoptosis is characterized. In addition, the dependence of AG126 protection on RNA transcription and tyrosine kinase inhibition is evaluated. Methods: Oxidative stress or apoptotic cell death was induced in ARPE–19 cells via treatment with H2O2, tBH, 7–ketosterol, or C2–ceramide. Cell health in the absence and presence of AG126, genestein, and/or Actinomycin D was monitored via WST–1 analysis. Results: ARPE–19 cells were protected from oxidative stress induced by H2O2 or tBH upon pretreatment with 20 to 50 µM AG126. AG126 did not protect ARPE–19 cells from oxysterol– or C2–ceramide–induced cell death. A minimum of 5 h pretreatment was required for AG126 protection, while concurrent treatment had no protective effect. Treatment with the broad range tyrosine kinase inhibitor, genestein, did not ameliorate the effects of H2O2 or tBH. Addition of actinomycin D, an RNA transcription inhibitor, blocked the protective effect of AG126. Conclusions: AG126 protects ARPE–19 cells from oxidative stress through a mechanism independent of tyrosine kinase inhibition but dependent upon gene expression. The pretreatment requirement indicates that AG126 is not acting as an antioxidant. The action of AG126 is likely to occur before the ceramide signaling cascade is triggered by H2O2 or tBH. Characterization of the intervening molecular mechanism may reveal relevant targets for therapeutic intervention in the management of both wet and dry forms of age–related macular degeneration.

Keywords: retinal pigment epithelium • oxidation/oxidative or free radical damage • age-related macular degeneration 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×