Peroxynitrite cytotoxicity on bovine retinal pigmented epithelial cells in culture.
Peroxynitrite induced in vitro a dose dependent toxicity on retinal pigmented epithelial (RPE) cells. Cell death was partially mediated by apoptosis as demonstrated by nuclear fragmentation and TdT-mediated dUTP nick-end labeling assay. Peroxynitrite-induced tyrosine nitration was revealed by immunocytochemistry, both in the cytoplasm and in the nucleus of the cells. Nitration was not observed in RPE cells, producing nitric oxide (NO) after stimulation by lipopolysacharide and interferon-g (IFN-gamma), suggesting that peroxynitrite was not formed in vitro in such conditions. Peroxynitrite could be responsible for the retinal damages observed in pathological conditions in which NO has been demonstrated to be involved. In this context, EGb761, identified as a free radical scavenger, was showed herein to protect RPE cells against peroxynitrite injury.
Behar-Cohen
F F
FF
INSERM U450, Développement, Vieillissement et Pathologie de la rétine, Centre de Gérontologie Association Claude Bernard, Paris, France.
Heydolph
S
S
Faure
V
V
Droy-Lefaix
M T
MT
Courtois
Y
Y
Goureau
O
O
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D020441:Ginkgo biloba; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009566:Nitrates / Q000633:toxicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine / Q000494:pharmacology; D000096983:Ginkgo Extract
D004247:DNA; D016166:Free Radical Scavengers; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D009566:Nitrates; D009569:Nitric Oxide; D010936:Plant Extracts; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C039642:peroxynitric acid