Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kamoshita, Mamoru, Ozawa, Yoko, Kubota, Shunsuke, Miyake, Seiji, Tsuda, Chiduru, Nagai, Norihiro, Yuki, Kenya, Shimmura, Shigeto, Umezawa, Kazuo, Tsubota, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782327386629472256
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
work_keys_str_mv AT kamoshitamamoru ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT ozawayoko ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT kubotashunsuke ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT miyakeseiji ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT tsudachiduru ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT nagainorihiro ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT yukikenya ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT shimmurashigeto ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT umezawakazuo ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation
AT tsubotakazuo ampknfkbaxisinthephotoreceptordisorderduringretinalinflammation