Reduction of p66Shc suppresses oxidative damage in retinal pigmented epithelial cells and retina

Zhihao Wu, Brian Rogers, Shu Kachi, Sean F. Hackett, Anna Sick, Peter A. Campochiaro

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The largest isoform of the Shc adapter protein, p66Shc, has been implicated in oxidative damage-induced apoptosis in vital organs, because mice deficient in p66Shc have a 30% increase in life span and are resistant to the lethal effects of systemically administered paraquat, a source of severe oxidative damage. In this study, we utilized siRNA directed against the CH2 domain of Shc, to reduce p66Shc, but not p52Shc nor p46Shc in retinal pigmented epithelial (RPE) cells. RPE cells deficient in p66Shc had reduced susceptibility to oxidative stress-induced apoptosis. Compared to control cells, those with reduced p66Shc had increased basal and oxidative stress-induced NF-κB transcriptional activity, increased levels of antioxidant enzymes, and less generation of reactive oxygen species when challenged with H2O 2. The increase in oxidative stress-induced NF-κB activity was mediated by activation of ERK. Compared to eyes injected with GFP siRNA, those injected with p66Shc siRNA showed less loss of retinal function as assessed by electroretinograms from paraquat-induced oxidative stress. These data suggest that p66Shc and molecular signals involved in its regulation provide therapeutic targets for retinal degenerations in which oxidative-damage plays a major role, including age-related macular degeneration and cone cell death in retinitis pigmentosa.

Original languageEnglish (US)
Pages (from-to)996-1005
Number of pages10
JournalJournal of Cellular Physiology
Issue number3
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Reduction of p66Shc suppresses oxidative damage in retinal pigmented epithelial cells and retina'. Together they form a unique fingerprint.

Cite this