Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells.
The degeneration of the retinal pigment epithelium caused by oxidative damage is a stage of development in age-related macular degeneration (AMD). The carotenoid lutein is a major macular pigment that may reduce the incidence and progression of AMD, but the underlying mechanism is currently still not fully understood. Carotenoids are known to be direct antioxidants. However, carotenoids can also activate cellular pathways resulting in indirect antioxidant effects. Here, we investigate the influence of lutein on the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes in human retinal pigment epithelial cells (ARPE-19 cells) using lutein-loaded Tween40 micelles. The micelles were identified as a suitable delivery system since they were non-toxic in APRE-19 cells up to 0.04% Tween40 and led to a cellular lutein accumulation of 62 µM ± 14 µM after 24 h. Lutein significantly enhanced Nrf2 translocation to the nucleus 1.5 ± 0.4-fold compared to unloaded micelles after 4 h. Furthermore, lutein treatment for 24 h significantly increased the transcripts of NAD(P)H:quinone oxidoreductase 1 (NQO1) by 1.7 ± 0.1-fold, glutamate-cysteine ligase regulatory subunit (GCLm) by 1.4 ± 0.1-fold, and heme oxygenase-1 (HO-1) by 1.8 ± 0.3-fold. Moreover, we observed a significant enhancement of NQO1 activity by 1.2 ± 0.1-fold. Collectively, this study indicates that lutein not only serves as a direct antioxidant, but also activates Nrf2 in ARPE-19 cells.
Frede, K.; Ebert, F.; Kipp, A.; Tanja Schwerdtle, T; Baldermann, S. 2017. Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells. Journal of Agricultural and Food Chemistry 65, 5944-5952.