Peer-Reviewed Journal Details
Mandatory Fields
Mackey, AM,Sanvicens, N,Groeger, G,Doonan, F,Wallace, D,Cotter, TG;
2008
March
Cell
Redox survival signalling in retina-derived 661W cells
Validated
()
Optional Fields
AKT hydrogen peroxide survival signalling STRESS-INDUCED APOPTOSIS TUMOR-SUPPRESSOR PTEN OXIDATIVE STRESS PHOTORECEPTOR APOPTOSIS INSULIN STIMULATION PEROXIDE ACTIVATION PATHWAYS DEATH H2O2
15
1291
1303
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 prosurvival 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.
DOI 10.1038/cdd.2008.43
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