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SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway

L Cao1, C Liu, F Wang

  • 1Tenth People's Hospital, School of Medicine, Affiliate of Tongji University, Department of Ophthalmology, Shanghai, China.

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas
|September 17, 2013
PubMed

Insights

Sirtuin 1 (SIRT1) activation protects against amyloid-beta (Aβ) induced inflammation and retinal degeneration in age-related macular degeneration (AMD). SRT1720, a SIRT1 activator, inhibited Aβ-mediated inflammation and barrier disruption in retinal pigment epithelial cells.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Biology

Background:

  • Chronic inflammation driven by amyloid-beta (Aβ) is implicated in age-related macular degeneration (AMD).
  • Matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) are potential mediators of inflammation in AMD.
  • Sirtuin 1 (SIRT1) regulates inflammation by inhibiting nuclear factor-kappa B (NF-κB) signaling.

Purpose of the Study:

  • To investigate if SIRT1 signaling activation mediates the protective effects of resveratrol against Aβ-induced retinal degeneration.
  • To determine the role of SIRT1 in abrogating Aβ-induced inflammation in human adult retinal pigment epithelial (RPE) cells.

Main Methods:

  • Human adult RPE cells were exposed to Aβ.
  • SIRT1 activity was modulated through overactivation and knockdown.
  • The effect of SIRT1 activator SRT1720 on Aβ-induced cellular changes was assessed.
  • NF-κB activation and IκBα levels were analyzed.

Main Results:

  • SRT1720 abrogated Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9.
  • These protective effects were not observed in SIRT1-silenced RPE cells.
  • SRT1720 inhibited Aβ-mediated NF-κB activation and prevented the decrease of IκBα.

Conclusions:

  • SIRT1 signaling plays a protective role in mitigating Aβ-dependent retinal degeneration and inflammation associated with AMD.
  • Targeting SIRT1 may offer a therapeutic strategy for managing AMD.
  • The findings highlight the importance of the SIRT1/NF-κB pathway in RPE cell response to Aβ.

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