Excitotoxicity-associated p53 expression in adult rat retina is mediated by calpain activity but not by Cl- influx.
We have previously demonstrated an important role of influx of Cl(-) rather than Ca(2+) in acute excitotoxicity in adult rat retina. As p53 has been implicated in delayed apoptotic cell death, here we examined the appearance of p53 immunoreactivity in a rat eyecup preparation. Kainate induced p53 expression in a subpopulation of ganglion cells and other cells in the ganglion cell layer. Application of a calpain inhibitor, but not reduction of extracellular Cl(-), markedly inhibited kainate-induced p53 expression. The results suggest that, in contrast to acute excitotoxicity, delayed excitotoxicity in retinal neurons is mediated by Ca(2+)-dependent processes, including calpain activation.
Hama
Yasuhiro
Y
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto, Japan.
Katsuki
Hiroshi
H
Izumi
Yasuhiko
Y
Kume
Toshiaki
T
Akaike
Akinori
A
D000818:Animals; D002154:Calpain / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D002712:Chlorides; D018690:Excitatory Amino Acid Agonists; D016159:Tumor Suppressor Protein p53; D002154:Calpain; D007608:Kainic Acid