文章基本信息

标题：Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts
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作者：Kim, Hyeon Ho ; Shin, Chung Min ; Park, Chi-Hyun 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2005
卷号：46
期号：08
页码：1712-1720
DOI：10.1194/jlr.M500105-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Ultraviolet (UV) irradiation regulates UV-responsive genes,including matrix metalloproteinases (MMPs). Moreover, UV-inducedMMPs cause connective tissue damage and the skin to become wrinkledand aged. Here, we investigated the effect of eicosapentaenoicacid (EPA), a dietary ${omega}$ -3 fatty acid, on UV-induced MMP-1 expressionin human dermal fibroblasts (HDFs). We found that UV radiationincreases MMP-1 expression and that this is mediated by p44and p42 MAP kinase (ERK) and Jun-N-terminal kinase (JNK) activationbut not by p38 activation. Pretreatment of HDFs with EPA inhibitedUV-induced MMP-1 expression in a dose-dependent manner and alsoinhibited the UV-induced activation of ERK and JNK by inhibitingERK kinase (MEK1) and SAPK/ERK kinase 1 (SEK1) activation, respectively.Moreover, inhibition of ERK and JNK by EPA resulted in the decreaseof c-Fos expression and c-Jun phosphorylation/expression inducedby UV, respectively, which led to the inhibition of UV-inducedactivator protein-1 DNA binding activity. This inhibitory effectof EPA on MMP-1 was not mediated by an antioxidant effect. Wealso found that EPA inhibited 12-O-tetradecanoylphorbol-13-acetate-or tumor necrosis factor- ${alpha}$ -induced MMP-1 expression in HDFs andUV-induced MMP-1 expression in HaCaT cells. In conclusion, our results demonstrate that EPA can inhibitUV-induced MMP-1 expression by inhibiting the MEK1/ERK/c-Fosand SEK1/JNK/c-Jun pathways. Therefore, EPA is a potential agentfor the prevention and treatment of skin aging. Abbreviations: AA, arachidonic acid; AP-1, activator protein-1; COX-2, cyclooxygenase-2; DCF-DA, 2'-7'-dichlorofluorescein diacetate; DHA, docosahexaenoic acid; EMSA, electrophoretic mobility shift assay; EPA, eicosapentaenoic acid; ERK, p44 and p42 MAP kinase; JNK, Jun-N-terminal kinase; HDF, human dermal fibroblast; LA, linolenic acid; MAPK, mitogen-activated protein kinase; MEK1, MAP or ERK kinase; MMP-1, matrix metalloproteinase-1; NAC, N-acetyl cysteine; OA, oleic acid; PGE, prostaglandin E; PMSF, phenylmethylsulfonyl fluoride; ROS, reactive oxygen species; SEK, SAPK/ERK kinase; TNF- ${alpha}$ , tumor necrosis factor- ${alpha}$ ; TPA, 12-O-tetradecanoylphorbol-13-acetate; UV, ultraviolet Supplementary key words ultraviolet radiation • matrix metalloproteinase-1 • polyunsaturated fatty acid