Ouabain induces an increase of retinal ganglion cell survival in vitro: the involvement of protein kinase C.
Ouabain is a steroid derivative that can regulate many cellular events such as growth and proliferation. It modulates Na+,K+-ATPase activity leading to the activation of different intracellular pathways through protein-protein interactions that have been characterized during the last few years. The aim of this work was to study the role of ouabain in rat retinal ganglion cell survival after 48 h in culture. Our results demonstrated that ouabain significantly induced an increase in retinal ganglion cell survival. The effect was dose-dependent and was maximal with 3.0 nM. The blockade of protein kinase C activity by 1.25 microM chelerythrine chloride abolished the ouabain effect, indicating an involvement of this intracellular pathway. None of the protein kinase inhibitors usually employed in the study of ouabain-driven intracellular pathways (PD98059, Ly294002, herbimycin, and genistein) was able to influence neuronal survival induced by ouabain. The data presented suggest that ouabain may be the trigger of an intracellular pathway responsible for neuronal survival.
de Rezende Corrêa
Gustavo
G
Departamento de Neurobiologia, Programa de Neuroimunologia, Instituto de Biologia, Centro de Estudos Gerais, Universidade Federal Fluminense, CP: 100180 CEP: 24001-970, Niterói-Rio de Janeiro, Brazil.
Araujo dos Santos
Aline
A
Frederico Leite Fontes
Carlos
C
Giestal de Araujo
Elizabeth
E
D000704:Analysis of Variance; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010042:Ouabain; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C