Redox survival signalling in retina-derived 661W cells.
Reactive oxygen species have been implicated in processes involving cellular damage and subsequent cell death, especially in organs such as the eye that are constantly exposed to excitatory signals. However, recent studies have shown that oxidant species can also act as intracellular signalling molecules promoting cell survival, but little is known about this mechanism in the retina. The present study demonstrates for the first time that hydrogen peroxide (H2O2) is generated rapidly and acts as a pro-survival signal in response to a variety of apoptotic stimuli in retina-derived 661W cells and in the retinal ganglion cell line RGC-5. Focussing on 661Ws and serum deprivation, we systematically investigated pro-survival and pro-death pathways and discovered that the rapid and transient burst of H2O2 activates the AKT survival pathway. Activation of the apoptotic machinery takes place following the decline of H2O2 to basal levels. To substantiate this proposed pro-survival role of H2O2, we inhibited the oxidant burst, which exacerbated cell death. Conversely, maintenance of the oxidant signal using exogenous H2O2 enhanced cell survival. Overall, the results presented in this study provide evidence for a novel role of H2O2 in mediating survival of retinal cells in response to apoptotic stimuli.
Mackey
A M
AM
Laboratory of Cell Development and Disease, Department of Biochemistry, Bioscience Research Institute, University College Cork, Cork, Ireland.
Sanvicens
N
N
Groeger
G
G
Doonan
F
F
Wallace
D
D
Cotter
T G
TG
D000818:Animals; D017209:Apoptosis; D001578:Benzopyrans / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
D001578:Benzopyrans; C120400:CR 6; D008562:Membrane Glycoproteins; D009861:Onium Compounds; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D002154:Calpain