title: Fucoxanthin enhances the level of reduced glutathione via the Nrf2-mediated pathway in human keratinocytes.
abstract: Fucoxanthin, a natural carotenoid, is abundant in seaweed with antioxidant properties. This study investigated the role of fucoxanthin in the induction of antioxidant enzymes involved in the synthesis of reduced glutathione (GSH), synthesized by glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS), via Akt/nuclear factor-erythroid 2-related (Nrf2) pathway in human keratinocytes (HaCaT) and elucidated the underlying mechanism. Fucoxanthin treatment increased the mRNA and protein levels of GCLC and GSS in HaCaT cells. In addition, fucoxanthin treatment promoted the nuclear translocation and phosphorylation of Nrf2, a transcription factor for the genes encoding GCLC and GSS. Chromatin immune-precipitation and luciferase reporter gene assays revealed that fucoxanthin treatment increased the binding of Nrf2 to the antioxidant response element (ARE) sequence and transcriptional activity of Nrf2. Fucoxanthin treatment increased phosphorylation of Akt (active form), an up-regulator of Nrf2 and exposure to LY294002, a phosphoinositide 3-kinase (PI3K)/Akt inhibitor, suppressed the fucoxanthin-induced activation of Akt, Nrf2, resulting in decreased GCLC and GSS expression. In accordance with the effects on GCLC and GSS expression, fucoxanthin induced the level of GSH. In addition, fucoxanthin treatment recovered the level of GSH reduced by ultraviolet B irradiation. Taken together, these findings suggest that fucoxanthin treatment augments cellular antioxidant defense by inducing Nrf2-driven expression of enzymes involved in GSH synthesis via PI3K/Akt signaling.
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Korea. zhengjian0317@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Korea. mjpiao@hanmail.net.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Korea. svv771@hotmail.com.
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Korea. vane1989923@hotmail.com.
authors.forename: Cheng Wen
authors.initials: CW
authors.lastname: Yao
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Korea. cjw102700@hanmail.net.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Cha
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Korea. jinwonh@jejunu.ac.kr.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D061745:Antioxidant Response Elements; D002478:Cells, Cultured; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000378:metabolism*; D005981:Glutathione Synthase / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D024341:Xanthophylls / Q000494:pharmacology*
chemical_list: D051267:NF-E2-Related Factor 2; D024341:Xanthophylls; C025164:fucoxanthin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione