Publication: Activation of Nrf2 reduces UVA-mediated MMP-1 upregulation via MAPK/AP-1 signaling cascades: The photoprotective effects of sulforaphane and hispidulins
Issued Date
2017-03-01
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ISSN
15210103
00223565
00223565
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2-s2.0-85012868990
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Pharmacology and Experimental Therapeutics. Vol.360, No.3 (2017), 388-398
Suggested Citation
Anyamanee Chaiprasongsuk, Jinaphat Lohakul, Kitipong Soontrapa, Somponnat Sampattavanich, Pravit Akarasereenont, Uraiwan Panich Activation of Nrf2 reduces UVA-mediated MMP-1 upregulation via MAPK/AP-1 signaling cascades: The photoprotective effects of sulforaphane and hispidulins. Journal of Pharmacology and Experimental Therapeutics. Vol.360, No.3 (2017), 388-398. doi:10.1124/jpet.116.238048 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41954
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Title
Activation of Nrf2 reduces UVA-mediated MMP-1 upregulation via MAPK/AP-1 signaling cascades: The photoprotective effects of sulforaphane and hispidulins
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Abstract
© 2017 by The American Society for Pharmacology and Experimental Therapeutics. UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediatedMMP-1 upregulation via activation of mitogenactivated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVAirradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVAmediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates.