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 -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--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-, tumor necrosis factor-; TPA, 12-O-tetradecanoylphorbol-13-acetate; UV, ultraviolet
Supplementary key words ultraviolet radiation • matrix metalloproteinase-1 • polyunsaturated fatty acid
-3 fatty acid, on UV-induced MMP-1 expression in human dermal fibroblasts (HDFs). We found that UV radiation increases MMP-1 expression and that this is mediated by p44 and p42 MAP kinase (ERK) and Jun-N-terminal kinase (JNK) activation but not by p38 activation. Pretreatment of HDFs with EPA inhibited UV-induced MMP-1 expression in a dose-dependent manner and also inhibited the UV-induced activation of ERK and JNK by inhibiting ERK kinase (MEK1) and SAPK/ERK kinase 1 (SEK1) activation, respectively. Moreover, inhibition of ERK and JNK by EPA resulted in the decrease of c-Fos expression and c-Jun phosphorylation/expression induced by UV, respectively, which led to the inhibition of UV-induced activator protein-1 DNA binding activity. This inhibitory effect of EPA on MMP-1 was not mediated by an antioxidant effect. We also found that EPA inhibited 12-O-tetradecanoylphorbol-13-acetate- or tumor necrosis factor-
-induced MMP-1 expression in HDFs and UV-induced MMP-1 expression in HaCaT cells.
In conclusion, our results demonstrate that EPA can inhibit UV-induced MMP-1 expression by inhibiting the MEK1/ERK/c-Fos and SEK1/JNK/c-Jun pathways. Therefore, EPA is a potential agent for 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-
