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Naringenin targets ERK2 and suppresses UVB‐induced photoaging

A number of natural phytochemicals have anti‐photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase‐1 (MMP‐1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid foun...

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Autores principales: Jung, Sung Keun, Ha, Su Jeong, Jung, Chang Hwa, Kim, Yun Tai, Lee, Hoo‐Keun, Kim, Myoung Ok, Lee, Mee‐Hyun, Mottamal, Madhusoodanan, Bode, Ann M., Lee, Ki Won, Dong, Zigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831363/
https://www.ncbi.nlm.nih.gov/pubmed/26861188
http://dx.doi.org/10.1111/jcmm.12780
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author Jung, Sung Keun
Ha, Su Jeong
Jung, Chang Hwa
Kim, Yun Tai
Lee, Hoo‐Keun
Kim, Myoung Ok
Lee, Mee‐Hyun
Mottamal, Madhusoodanan
Bode, Ann M.
Lee, Ki Won
Dong, Zigang
author_facet Jung, Sung Keun
Ha, Su Jeong
Jung, Chang Hwa
Kim, Yun Tai
Lee, Hoo‐Keun
Kim, Myoung Ok
Lee, Mee‐Hyun
Mottamal, Madhusoodanan
Bode, Ann M.
Lee, Ki Won
Dong, Zigang
author_sort Jung, Sung Keun
collection PubMed
description A number of natural phytochemicals have anti‐photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase‐1 (MMP‐1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB‐induced MMP‐1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3‐dimensional (3‐D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm(2)) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB‐induced MMP‐1 expression and AP‐1 activity, and strongly suppressed UVB‐induced phosphorylation of Fos‐related antigen (FRA)‐1 at Ser265. Importantly, UVB irradiation‐induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen‐activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB‐induced extracellular signal‐regulated kinase 2 (ERK2) activity and subsequently attenuated UVB‐induced phosphorylation of p90(RSK) by competitively binding with ATP. Constitutively active MEK (CA‐MEK) increased FRA1 phosphorylation and expression and also induced MMP‐1 expression, whereas dominant‐negative ERK2 (DN‐ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP‐1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB‐induced wrinkle formation, trans‐epidermal water loss and MMP‐13 expression. Naringenin exerts potent anti‐photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down‐regulation of AP‐1 transactivation and MMP‐1 expression.
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spelling pubmed-48313632016-05-01 Naringenin targets ERK2 and suppresses UVB‐induced photoaging Jung, Sung Keun Ha, Su Jeong Jung, Chang Hwa Kim, Yun Tai Lee, Hoo‐Keun Kim, Myoung Ok Lee, Mee‐Hyun Mottamal, Madhusoodanan Bode, Ann M. Lee, Ki Won Dong, Zigang J Cell Mol Med Original Articles A number of natural phytochemicals have anti‐photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase‐1 (MMP‐1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB‐induced MMP‐1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3‐dimensional (3‐D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm(2)) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB‐induced MMP‐1 expression and AP‐1 activity, and strongly suppressed UVB‐induced phosphorylation of Fos‐related antigen (FRA)‐1 at Ser265. Importantly, UVB irradiation‐induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen‐activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB‐induced extracellular signal‐regulated kinase 2 (ERK2) activity and subsequently attenuated UVB‐induced phosphorylation of p90(RSK) by competitively binding with ATP. Constitutively active MEK (CA‐MEK) increased FRA1 phosphorylation and expression and also induced MMP‐1 expression, whereas dominant‐negative ERK2 (DN‐ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP‐1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB‐induced wrinkle formation, trans‐epidermal water loss and MMP‐13 expression. Naringenin exerts potent anti‐photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down‐regulation of AP‐1 transactivation and MMP‐1 expression. John Wiley and Sons Inc. 2016-02-10 2016-05 /pmc/articles/PMC4831363/ /pubmed/26861188 http://dx.doi.org/10.1111/jcmm.12780 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Jung, Sung Keun
Ha, Su Jeong
Jung, Chang Hwa
Kim, Yun Tai
Lee, Hoo‐Keun
Kim, Myoung Ok
Lee, Mee‐Hyun
Mottamal, Madhusoodanan
Bode, Ann M.
Lee, Ki Won
Dong, Zigang
Naringenin targets ERK2 and suppresses UVB‐induced photoaging
title Naringenin targets ERK2 and suppresses UVB‐induced photoaging
title_full Naringenin targets ERK2 and suppresses UVB‐induced photoaging
title_fullStr Naringenin targets ERK2 and suppresses UVB‐induced photoaging
title_full_unstemmed Naringenin targets ERK2 and suppresses UVB‐induced photoaging
title_short Naringenin targets ERK2 and suppresses UVB‐induced photoaging
title_sort naringenin targets erk2 and suppresses uvb‐induced photoaging
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831363/
https://www.ncbi.nlm.nih.gov/pubmed/26861188
http://dx.doi.org/10.1111/jcmm.12780
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