ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.

In this study, we examined the role of Fas apoptotic inhibitory molecule 2 (Faim2), an inhibitor of the Fas signaling pathway, and its regulation by stress kinase signaling during Fas-mediated apoptosis of 661W cells, an immortalized photoreceptor-like cell line Treatment of 661W cells with a Fas-ac...

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Main Authors: Cagri G Besirli, Qiong-Duon Zheng, David M Reed, David N Zacks
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3460913?pdf=render
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spelling doaj-fa9f0f714b2b479386ab54c57ad445452020-11-24T20:50:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4666410.1371/journal.pone.0046664ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.Cagri G BesirliQiong-Duon ZhengDavid M ReedDavid N ZacksIn this study, we examined the role of Fas apoptotic inhibitory molecule 2 (Faim2), an inhibitor of the Fas signaling pathway, and its regulation by stress kinase signaling during Fas-mediated apoptosis of 661W cells, an immortalized photoreceptor-like cell line 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 a pharmacological inhibitor 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 knockdown, Fas activating antibody treatment resulted in earlier and more robust caspase activation, and increased cell death. These results demonstrate that Faim2 acts as a neuroprotectant during Fas-mediated apoptosis of 661W cells. The expression of Faim2 is triggered, at least in part, by Fas-receptor activation and subsequent ERK signaling. Our findings identify a novel protective pathway that auto-regulates Fas-induced photoreceptor apoptosis in vitro. Modulation of this pathway to increase Faim2 expression may be a potential therapeutic option to prevent photoreceptor death.http://europepmc.org/articles/PMC3460913?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Cagri G Besirli
Qiong-Duon Zheng
David M Reed
David N Zacks
spellingShingle Cagri G Besirli
Qiong-Duon Zheng
David M Reed
David N Zacks
ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.
PLoS ONE
author_facet Cagri G Besirli
Qiong-Duon Zheng
David M Reed
David N Zacks
author_sort Cagri G Besirli
title ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.
title_short ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.
title_full ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.
title_fullStr ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.
title_full_unstemmed ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.
title_sort erk-mediated activation of fas apoptotic inhibitory molecule 2 (faim2) prevents apoptosis of 661w cells in a model of detachment-induced photoreceptor cell death.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description In this study, we examined the role of Fas apoptotic inhibitory molecule 2 (Faim2), an inhibitor of the Fas signaling pathway, and its regulation by stress kinase signaling during Fas-mediated apoptosis of 661W cells, an immortalized photoreceptor-like cell line 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 a pharmacological inhibitor 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 knockdown, Fas activating antibody treatment resulted in earlier and more robust caspase activation, and increased cell death. These results demonstrate that Faim2 acts as a neuroprotectant during Fas-mediated apoptosis of 661W cells. The expression of Faim2 is triggered, at least in part, by Fas-receptor activation and subsequent ERK signaling. Our findings identify a novel protective pathway that auto-regulates Fas-induced photoreceptor apoptosis in vitro. Modulation of this pathway to increase Faim2 expression may be a potential therapeutic option to prevent photoreceptor death.
url http://europepmc.org/articles/PMC3460913?pdf=render
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