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Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells
journal contribution
posted on 2017-06-30, 00:00 authored by Katja Frede, Franziska Ebert, Anna P. Kipp, Tanja Schwerdtle, Susanne BaldermannThe 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 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 nontoxic 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 that of 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.