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Abstract #22720 Published in IGR 11-1
Glutamate-induced NFκB activation in the retina
Fan W; Cooper NGInvestigative Ophthalmology and Visual Science 2009; 50: 917-925
PURPOSE: To determine the distribution and glutamate-mediated activation of nuclear factor (NF) κB members in the retina and pan-purified retinal ganglion cells (RGCs) and to characterize steps in the signal transduction events that lead to NFκB activation. METHODS: Retinal expression patterns and RGCs were evaluated for five NFκB proteins with the aid of immunohistochemistry. Retinal explants or RGCs were treated with glutamate with or without the presence of the NDMA receptor antagonist memantine, the calcium chelator EGTA, or a specific inhibitor for calcium/calmodulin-dependent protein kinase-II (CaMKII). Characterizations of NFκB activation were performed with the aid of electrophoretic mobility shift assays and supershift assays. RESULTS: All five NFκB proteins were present in the retina and in the pan-purified RGCs. In response to a glutamate stimulus, all NFκB proteins except c-Rel were activated. P65 was unique in that it was not constitutively active but showed a glutamate-inducible activation in the retina and in the cultured RGCs. Memantine, EGTA, or autocamtide-2-related inhibitory peptide (AIP) inhibited NFκB activation in the retina. Furthermore, AIP significantly reduced the level of glutamate-induced degradation of IκBs. CONCLUSIONS: These data indicate that glutamate activates distinct NFκB proteins in the retina. P65 activation may be especially important with regard to RGC responses to glutamate given that its activity is induced by conditions known to lead to the death of these cells. The NMDA receptor-Ca2+-CaMKII signaling pathway is involved in glutamate-induced NFκB activation. Because AIP blocks the degradation of IκB, its regulation is clearly downstream of CaMKII.
Dr. W. Fan, Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA
Classification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)
