Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.

Details

Serval ID
serval:BIB_151C4F6CE5E4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.
Journal
Transplantation
Author(s)
Bourges J.L., Torriglia A., Valamanesh F., Benezra D., Renard G., Behar-Cohen F.F.
ISSN
0041-1337 (Print)
ISSN-L
0041-1337
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
84
Number
3
Pages
415-423
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death.
METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count.
RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection.
CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.
Keywords
Animals, Apoptosis/drug effects, Apoptosis/physiology, Cell Survival/drug effects, Cell Survival/physiology, Corneal Transplantation/pathology, Corneal Transplantation/physiology, Endothelium, Corneal/cytology, Endothelium, Corneal/drug effects, Graft Rejection/pathology, Graft Rejection/physiopathology, Humans, Imines/pharmacology, Nitric Oxide/metabolism, Nitric Oxide Synthase Type II/antagonists & inhibitors, Nitrosation, Peroxynitrous Acid/pharmacology, Peroxynitrous Acid/physiology, Rats, Rats, Inbred BN, Rats, Inbred Lew
Pubmed
Web of science
Create date
27/08/2013 14:42
Last modification date
20/08/2019 12:44
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