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Cagri G. Besirli, Qiong-Duon Zheng, David N. Zacks; ERK-mediated Activation of Fas Apoptosis Inhibitory Molecule (Faim2) Prevents Photoreceptor Apoptosis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1136.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the role of Fas apoptosis inhibitory molecule 2 (Faim2), an inhibitor of the Fas signaling pathway, and its regulation by stress kinase signaling during Fas-mediated apoptosis of photoreceptors.
Photoreceptor (661W) cells were treated with a Fas-receptor activating antibody and the levels of Faim2 were examined. Activation of the stress-kinase pathways was assayed by immunoblotting of kinases and their downstream targets. The levels of Faim2 were examined in the presence of stress-kinase inhibitors in Fas-treated 661W cells. The effect of stress-kinase inhibition on Fas-mediated photoreceptor apoptosis was evaluated by caspase 8 activation and measuring cell viability. Faim2 expression was inhibited by siRNA knock-down in 661W cells and caspase 8 activation was measured after Fas activating antibody treatment.
Treatment of 661W cells with a Fas-activating antibody led to increased levels of Faim2. Both ERK and JNK stress kinase pathways were activated in Fas-treated 661W cells, but only the inhibition of the ERK pathway reduced the levels of Faim2. Blocking the ERK pathway using pharmacological inhibitors increased the susceptibility of 661W cells to Fas-induced caspase activation and apoptosis. When the levels of Faim2 were reduced in 661W cells by siRNA knock-down, Fas activating antibody treatment resulted in earlier and more robust caspase 8 activation.
Faim2 acts as a neuroprotectant during Fas-mediated apoptosis of photoreceptors. The expression of Faim2 is regulated, at least in part, by the ERK signaling pathway. Modulation of ERK signaling to increase Faim2 expression may be a potential therapeutic option to prevent photoreceptor death.
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