SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000800659 |
Resumo: | Chronic inflammation induced by amyloid-beta (Aβ) plays a key role in the development of age-related macular degeneration (AMD), and matrix metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via inhibition of nuclear factor-kappa B (NF-κB) signaling, and resveratrol has been reported to prevent Aβ-induced retinal degeneration; therefore, we investigated whether this action was mediated via activation of SIRT1 signaling. Human adult retinal pigment epithelial (RPE) cells were exposed to Aβ, and overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1 is required for abrogating Aβ-induced inflammation. We found that Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were abrogated by the SIRT1 activator SRT1720, whereas alterations induced by Aβ in SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720 inhibited Aβ-mediated NF-κB activation and decrease of the NF-κB inhibitor, IκBα. Our findings suggest a protective role for SIRT1 signaling in Aβ-dependent retinal degeneration and inflammation in AMD. |
id |
ABDC-1_3d00dee76df2b31c7f19c88cffebfba4 |
---|---|
oai_identifier_str |
oai:scielo:S0100-879X2013000800659 |
network_acronym_str |
ABDC-1 |
network_name_str |
Brazilian Journal of Medical and Biological Research |
repository_id_str |
|
spelling |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathwayAmyloid-betaSRT1720Age-related macular degenerationBarrier integrityTight junctionMatrix metalloproteinase-9Chronic inflammation induced by amyloid-beta (Aβ) plays a key role in the development of age-related macular degeneration (AMD), and matrix metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via inhibition of nuclear factor-kappa B (NF-κB) signaling, and resveratrol has been reported to prevent Aβ-induced retinal degeneration; therefore, we investigated whether this action was mediated via activation of SIRT1 signaling. Human adult retinal pigment epithelial (RPE) cells were exposed to Aβ, and overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1 is required for abrogating Aβ-induced inflammation. We found that Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were abrogated by the SIRT1 activator SRT1720, whereas alterations induced by Aβ in SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720 inhibited Aβ-mediated NF-κB activation and decrease of the NF-κB inhibitor, IκBα. Our findings suggest a protective role for SIRT1 signaling in Aβ-dependent retinal degeneration and inflammation in AMD.Associação Brasileira de Divulgação Científica2013-08-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000800659Brazilian Journal of Medical and Biological Research v.46 n.8 2013reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/1414-431X20132903info:eu-repo/semantics/openAccessCao,L.Liu,C.Wang,F.Wang,H.eng2015-10-26T00:00:00Zoai:scielo:S0100-879X2013000800659Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2015-10-26T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway |
title |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway |
spellingShingle |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway Cao,L. Amyloid-beta SRT1720 Age-related macular degeneration Barrier integrity Tight junction Matrix metalloproteinase-9 |
title_short |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway |
title_full |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway |
title_fullStr |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway |
title_full_unstemmed |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway |
title_sort |
SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway |
author |
Cao,L. |
author_facet |
Cao,L. Liu,C. Wang,F. Wang,H. |
author_role |
author |
author2 |
Liu,C. Wang,F. Wang,H. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Cao,L. Liu,C. Wang,F. Wang,H. |
dc.subject.por.fl_str_mv |
Amyloid-beta SRT1720 Age-related macular degeneration Barrier integrity Tight junction Matrix metalloproteinase-9 |
topic |
Amyloid-beta SRT1720 Age-related macular degeneration Barrier integrity Tight junction Matrix metalloproteinase-9 |
description |
Chronic inflammation induced by amyloid-beta (Aβ) plays a key role in the development of age-related macular degeneration (AMD), and matrix metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via inhibition of nuclear factor-kappa B (NF-κB) signaling, and resveratrol has been reported to prevent Aβ-induced retinal degeneration; therefore, we investigated whether this action was mediated via activation of SIRT1 signaling. Human adult retinal pigment epithelial (RPE) cells were exposed to Aβ, and overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1 is required for abrogating Aβ-induced inflammation. We found that Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were abrogated by the SIRT1 activator SRT1720, whereas alterations induced by Aβ in SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720 inhibited Aβ-mediated NF-κB activation and decrease of the NF-κB inhibitor, IκBα. Our findings suggest a protective role for SIRT1 signaling in Aβ-dependent retinal degeneration and inflammation in AMD. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-08-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000800659 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000800659 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1414-431X20132903 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.46 n.8 2013 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
_version_ |
1754302942144364544 |