The trophic effect of ouabain on retinal ganglion cell is mediated by EGF receptor and PKC delta activation.
It was already shown that ouabain treatment can stimulate PKC isoenzymes leading to the activation of intracellular pathways involved in cell survival, growth and proliferation. We have previously demonstrated that ouabain or PMA treatment increases retinal ganglion cell survival, an effect mediated by PKC activation. The aim of this work was to investigate the role of EGF receptors in the ouabain effect and also to study which PKC isoform is activated by treatment with ouabain and PMA. Our results show that 2.5 microM tyrphostin, 1.0 microM PP1, 4.0 microM U73122, 1.0 microM JNK inhibitor V and 2.0 microM rottlerin blocked the ouabain effect indicating an involvement of receptors for EGF, Src, PLC, JNK and PKC delta respectively. The effect of PMA was only abolished when cultures were treated with rottlerin or with the JNK inhibitor suggesting the involvement of PKC delta and JNK. These results indicate that PKC delta could be a key regulator of retinal ganglion cell survival.
Corrêa
Gustavo de Rezende
Gde R
Departamento de Neurobiologia, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
Cunha
Karinne Cristinne da Silva
KC
dos Santos
Aline Araujo
AA
de Araujo
Elizabeth Giestal
EG
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010042:Ouabain; D066246:ErbB Receptors; D051745:Protein Kinase C-delta