Sulforaphane inhibits blue light-induced inflammation and apoptosis by upregulating the SIRT1/PGC-1α/Nrf2 pathway and autophagy in retinal pigment epithelial cells

Toxicol Appl Pharmacol. 2021 Jun 15;421:115545. doi: 10.1016/j.taap.2021.115545. Epub 2021 Apr 22.


The present study elucidated mechanisms through which sulforaphane (SFN) protects retinal pigment epithelial (RPE) cells from blue light-induced impairment. SFN could activate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increase the expression of the heme oxygenease-1 (HO-1) gene and production of glutathione. SFN reduced blue light-induced oxidative stress, and effectively activated cytoprotective components including Nrf-2, HO-1, thioredoxin-1, and glutathione. The protective effect of SFN on blue light-induced injury was blocked by the Nrf2 inhibitor ML385, suggesting that the SFN-induced Nrf2 pathway is involved in the cytoprotective effect of SFN. SFN inhibited intercellular adhesion molecule-1 expression induced by TNF-α or blue light, suggesting the anti-inflammatory activity of SFN. The inhibitory effect of SFN was associated with the blocking of NF-κB p65 nuclear translocation in blue light-exposed RPE cells. SFN protected RPE cells from blue light-induced interruption of the mitochondrial membrane potential and reduction of the Bcl-2/Bax ratio and cleaved caspase-3 and PARP-1 expression, suggesting the antiapoptotic activity of SFN. SFN alone or together with blue light exposure increased the expression of the autophagy-related proteins LC3BII and p62. An autophagy inhibitor, 3-MA, inhibited the protective effect of SFN on blue light-induced cell damage. SFN increased sirtuin-1 (SIRT1) expression; however, treatment with blue light induced peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) expression. Our study results demonstrated that SFN exerts its protective effect under blue light exposure by maintaining the Nrf2-related redox state and upregulating SIRT1 and PGC-1α expression and autophagy.

Keywords: Apoptosis; Autophagy; Blue light; Nrf2; Retinal pigment epithelial cells; Sulforaphane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Autophagy / drug effects*
  • Autophagy / radiation effects
  • Coculture Techniques
  • Epithelial Cells / drug effects*
  • Epithelial Cells / enzymology
  • Epithelial Cells / pathology
  • Epithelial Cells / radiation effects
  • Glutathione / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Isothiocyanates / pharmacology*
  • Light
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / enzymology
  • Retinal Pigment Epithelium / pathology
  • Retinal Pigment Epithelium / radiation effects
  • Signal Transduction
  • Sirtuin 1 / metabolism*
  • Sulfoxides / pharmacology*
  • THP-1 Cells
  • Transcription Factor RelA / metabolism


  • Anti-Inflammatory Agents
  • ICAM1 protein, human
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RELA protein, human
  • Sulfoxides
  • Transcription Factor RelA
  • Intercellular Adhesion Molecule-1
  • SIRT1 protein, human
  • Sirtuin 1
  • sulforaphane
  • Glutathione