SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-B pathway
Braz. j. med. biol. res
;
46(8): 659-669, ago. 2013. graf
Article
Dans Anglais
| LILACS
| ID: lil-684523
ABSTRACT
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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Transduction du signal
/
Peptides bêta-amyloïdes
/
Facteur de transcription NF-kappa B
/
Épithélium pigmentaire de la rétine
/
Sirtuine-1
/
Inflammation
/
Dégénérescence maculaire
Limites du sujet:
Adulte
/
Humains
langue:
Anglais
Texte intégral:
Braz. j. med. biol. res
Thème du journal:
Biologie
/
Médicament
Année:
2013
Type:
Article
/
descriptif de projet
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