Selective blockade of CaMKII-alpha inhibits NMDA-induced caspase-3-dependent cell death but does not arrest PARP-1 activation or loss of plasma membrane selectivity in rat retinal neurons

Brain Research
Dennis J Goebel

Abstract

Calcium/calmodulin-dependent protein kinase II-alpha (CaMKII-alpha) has been implicated in a number of receptor mediated events in neurons. Pharmacological blockade of CaMKII-alpha has been shown to prevent phosphorylation of NMDA-R2A and R2B receptor subunits, suggesting that this enzyme may be linked to receptor trafficking of glutamate receptors and serve as a regulatory protein for neuronal cell death. In the retina, inhibition of CaMKII-alpha has been reported to be neuroprotective against NMDA-induced cell death by preventing the activation of the caspase-3 dependent pathway. However, the effects of CaMKII-alpha blockade on the caspase-3 independent, PARP-1 dependent and the non-programmed cell death pathways have not previously been investigated. In the present study, blockade of CaMKII-alpha with the highly specific antagonist myristoylated autocamtide-2-related inhibitory peptide (AIP) was used in a rat in vivo model of retinal toxicity to compare the effects of on NMDA-induced caspase-3-dependent, PARP-1 dependent and the non-programmed (necrosis) cell death pathways. Results confirmed that AIP fully attenuates caspase-3 activation for at least 8 h following NMDA insult and also significantly improves retinal ganglion...Continue Reading

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Citations

Feb 19, 2011·Molecules and Cells·Young Hee KimGyeong Jae Cho
Jul 25, 2015·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Jun LiSongping Yu
Mar 30, 2010·Journal of Neurochemistry·Anne-Caroline BesseroPeter G H Clarke
Jul 2, 2010·The Journal of Comparative Neurology·Dragana TrifunovićFrançois Paquet-Durand
Jan 10, 2020·The Journal of Experimental Medicine·Wei LiuWenbo Zhang
Feb 15, 2011·Molecular and Cellular Neurosciences·Nicole M Ashpole, Andy Hudmon

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