Astaxanthin analogs,adonixanthin and lycopene,activate Nrf2 to prevent light-induced photoreceptor degeneration

Carotenoids,in particular astaxanthin,possess potent antioxidant capabilities. astaxanthin also induces nf-e2-related factor 2 (nrf2),which plays a major regulatory role in the antioxidative response. however,little is known whether the carotenoid,by-products of astaxanthin,activate nrf2. toward this end,we screened eight astaxanthin analogs for nrf2 activation in murine photoreceptor cell line,661 w,by quantitative reverse transcription-polymerase chain reaction (qrt-pcr). in addition,we monitored cell death in 661 w cells pretreated with astaxanthin analogs or only pretreated for 6 h with astaxanthin analogs and then exposed to light. furthermore,we quantified the reactive oxygen species (ros) production. cell death was quantified after light exposure by nuclear staining. nrf2-controlled genes ho-1,nqo-1,and gclm by qrt-pcr and nrf2 in the nucleus were upregulated in 661 w cells exposed astaxanthin,adonixanthin,echinenone,and lycopene. moreover,astaxanthin,adonixanthin,echinenone,β-carotene,adonirubin,and lycopene,but not canthaxanthin,suppressed ros production and protected cells against light-induced damage. moreover,pretreatment with adonixanthin or lycopene only before light exposure protected against light-induced cell damage and nrf2 silencing canceled these effects. these findings indicate that the more potent astaxanthin analogs,adonixanthin and lycopene,protect against light-induced cell damage through not only an anti-oxidative response but also through nrf2 activation. © 2017 the authors