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AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation
Recent progress in molecular analysis has revealed the possible involvement of multiple inflammatory signaling pathways in pathogenesis of retinal degeneration. However, how aberrant signaling pathways cause tissue damage and dysfunction is still being elucidated. Here, we focus on 5′-adenosine mono...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105543/ https://www.ncbi.nlm.nih.gov/pubmed/25048039 http://dx.doi.org/10.1371/journal.pone.0103013 |
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author | Kamoshita, Mamoru Ozawa, Yoko Kubota, Shunsuke Miyake, Seiji Tsuda, Chiduru Nagai, Norihiro Yuki, Kenya Shimmura, Shigeto Umezawa, Kazuo Tsubota, Kazuo |
author_facet | Kamoshita, Mamoru Ozawa, Yoko Kubota, Shunsuke Miyake, Seiji Tsuda, Chiduru Nagai, Norihiro Yuki, Kenya Shimmura, Shigeto Umezawa, Kazuo Tsubota, Kazuo |
author_sort | Kamoshita, Mamoru |
collection | PubMed |
description | Recent progress in molecular analysis has revealed the possible involvement of multiple inflammatory signaling pathways in pathogenesis of retinal degeneration. However, how aberrant signaling pathways cause tissue damage and dysfunction is still being elucidated. Here, we focus on 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), originally recognized as a key regulator of energy homeostasis. AMPK is also modulated in response to inflammatory signals, although its functions in inflamed tissue are obscure. We investigated the role of activated AMPK in the retinal neural damage and visual function impairment caused by inflammation. For this purpose, we used a mouse model of lipopolysaccharide-induced inflammation in the retina, and examined the effects of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). During inflammation, activated AMPK in the neural retina was decreased, but AICAR treatment prevented this change. Moreover, the electroretinogram (ERG) a-wave response, representing photoreceptor function, showed visual dysfunction in this model that was prevented by AICAR. Consistently, the model showed shortened photoreceptor outer segments (OSs) with reduced levels of rhodopsin, a visual pigment concentrated in the OSs, in a post-transcriptional manner, and these effects were also prevented by AICAR. In parallel, the level of activated NF-κB increased in the retina during inflammation, and this increase was suppressed by AICAR. Treatment with an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) preserved the rhodopsin level during inflammation, suppressing NF-κB. These findings indicated that AMPK activation by AICAR and subsequent NF-κB inhibition had a protective effect on visual function, and that AMPK activation played a neuroprotective role during retinal inflammation. |
format | Online Article Text |
id | pubmed-4105543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41055432014-07-23 AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation Kamoshita, Mamoru Ozawa, Yoko Kubota, Shunsuke Miyake, Seiji Tsuda, Chiduru Nagai, Norihiro Yuki, Kenya Shimmura, Shigeto Umezawa, Kazuo Tsubota, Kazuo PLoS One Research Article Recent progress in molecular analysis has revealed the possible involvement of multiple inflammatory signaling pathways in pathogenesis of retinal degeneration. However, how aberrant signaling pathways cause tissue damage and dysfunction is still being elucidated. Here, we focus on 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), originally recognized as a key regulator of energy homeostasis. AMPK is also modulated in response to inflammatory signals, although its functions in inflamed tissue are obscure. We investigated the role of activated AMPK in the retinal neural damage and visual function impairment caused by inflammation. For this purpose, we used a mouse model of lipopolysaccharide-induced inflammation in the retina, and examined the effects of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). During inflammation, activated AMPK in the neural retina was decreased, but AICAR treatment prevented this change. Moreover, the electroretinogram (ERG) a-wave response, representing photoreceptor function, showed visual dysfunction in this model that was prevented by AICAR. Consistently, the model showed shortened photoreceptor outer segments (OSs) with reduced levels of rhodopsin, a visual pigment concentrated in the OSs, in a post-transcriptional manner, and these effects were also prevented by AICAR. In parallel, the level of activated NF-κB increased in the retina during inflammation, and this increase was suppressed by AICAR. Treatment with an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) preserved the rhodopsin level during inflammation, suppressing NF-κB. These findings indicated that AMPK activation by AICAR and subsequent NF-κB inhibition had a protective effect on visual function, and that AMPK activation played a neuroprotective role during retinal inflammation. Public Library of Science 2014-07-21 /pmc/articles/PMC4105543/ /pubmed/25048039 http://dx.doi.org/10.1371/journal.pone.0103013 Text en © 2014 Kamoshita et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kamoshita, Mamoru Ozawa, Yoko Kubota, Shunsuke Miyake, Seiji Tsuda, Chiduru Nagai, Norihiro Yuki, Kenya Shimmura, Shigeto Umezawa, Kazuo Tsubota, Kazuo AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation |
title | AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation |
title_full | AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation |
title_fullStr | AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation |
title_full_unstemmed | AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation |
title_short | AMPK-NF-κB Axis in the Photoreceptor Disorder during Retinal Inflammation |
title_sort | ampk-nf-κb axis in the photoreceptor disorder during retinal inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105543/ https://www.ncbi.nlm.nih.gov/pubmed/25048039 http://dx.doi.org/10.1371/journal.pone.0103013 |
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