The role of PKCζ in NMDA-induced retinal ganglion cell death: Prevention by aspirin View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-03-13

AUTHORS

P. Crisanti, O. Laplace, E. Lecain, L. Jonet, J. C. Jeanny, B. Omri

ABSTRACT

Intravitreal NMDA injection has been shown to induce the excitotoxic loss of retinal cells. The retinal ganglion cell apoptosis induced by NMDA is thought to play an important role in retinal ischemia injury and NMDA-injected rat has been used as a model of neuronal loss in diseases such as glaucoma. In this experimental model, we studied the early effects of NMDA leading to the degeneration of retinal ganglion cells. PKCζ regulates the NF-κB pathway in cellular responses to various stresses and we have shown that aspirin inhibits purified human PKCζ. We therefore investigated the molecular mechanism by which retinal cells limit ocular injury following NMDA treatment. We found that the NMDA-induced apoptosis of ganglion cells was mediated, at least partly, by PKCζ. This enzyme was activated early in the cellular response to NMDA. Prolonged activation was followed by PKCζ cleavage, and nuclear translocation of the C-terminal region of this protein—a critical event for the survival of retinal cells. We also found that pretreatment with aspirin or the coinjection of NMDA with a specific PKCζ inhibitor counteracted the effects of NMDA. These findings provide new insight into the role played by PKCζ in neuronal loss in glaucoma. More... »

PAGES

983-991

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10495-006-6750-2

DOI

http://dx.doi.org/10.1007/s10495-006-6750-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002731405

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16547586


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