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Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes

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...

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Autores principales: Zheng, Jian, Piao, Mei Jing, Kim, Ki Cheon, Yao, Cheng Wen, Cha, Ji Won, Hyun, Jin Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113824/
https://www.ncbi.nlm.nih.gov/pubmed/25028796
http://dx.doi.org/10.3390/md12074214
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author Zheng, Jian
Piao, Mei Jing
Kim, Ki Cheon
Yao, Cheng Wen
Cha, Ji Won
Hyun, Jin Won
author_facet Zheng, Jian
Piao, Mei Jing
Kim, Ki Cheon
Yao, Cheng Wen
Cha, Ji Won
Hyun, Jin Won
author_sort Zheng, Jian
collection PubMed
description 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.
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spelling pubmed-41138242014-07-29 Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes Zheng, Jian Piao, Mei Jing Kim, Ki Cheon Yao, Cheng Wen Cha, Ji Won Hyun, Jin Won Mar Drugs Article 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. MDPI 2014-07-15 /pmc/articles/PMC4113824/ /pubmed/25028796 http://dx.doi.org/10.3390/md12074214 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zheng, Jian
Piao, Mei Jing
Kim, Ki Cheon
Yao, Cheng Wen
Cha, Ji Won
Hyun, Jin Won
Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes
title Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes
title_full Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes
title_fullStr Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes
title_full_unstemmed Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes
title_short Fucoxanthin Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes
title_sort fucoxanthin enhances the level of reduced glutathione via the nrf2-mediated pathway in human keratinocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113824/
https://www.ncbi.nlm.nih.gov/pubmed/25028796
http://dx.doi.org/10.3390/md12074214
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