title: The daidzein metabolite, 6,7,4'-Trihydroxyisoflavone, is a novel inhibitor of PKCα in suppressing solar UV-induced matrix metalloproteinase 1.
abstract: Soy isoflavone is an attractive source of functional cosmetic materials with anti-wrinkle, whitening and skin hydration effects. After consumption, the majority of soy isoflavones are converted to their metabolites in the human gastrointestinal tract. To understand the physiological impact of soy isoflavone on the human body, it is necessary to evaluate and address the biological function of its metabolites. In this study, we investigated the effect of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF), a major metabolite of daidzein, against solar UV (sUV)-induced matrix metalloproteinases (MMPs) in normal human dermal fibroblasts. MMPs play a critical role in the degradation of collagen in skin, thereby accelerating the aging process of skin. The mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MKK)3/6/p38 and MKK4/c-Jun N-terminal kinases (JNK) signaling pathways are known to modulate MMP-1 function, and their activation by sUV was significantly reduced by 6,7,4'-THIF pretreatment. Our results also indicated that the enzyme activity of protein kinase C (PKC)α, an upstream regulator of MKKs signaling, is suppressed by 6,7,4'-THIF using the in vitro kinase assay. Furthermore, the direct interaction between 6,7,4'-THIF and endogenous PKCα was confirmed using the pull-down assay. Not only sUV-induced MMP-1 expression, but also sUV-induced signaling pathway activation were decreased in PKCα knockdown cells. Overall, we elucidated the inhibitory effect of 6,7,4'-THIF on sUV-induced MMPs and suggest PKCα as its direct molecular target.
authors.affiliation: World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Korea. tglim83@gmail.com.
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Lim
authors.affiliation: World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Korea. idonlike@gmail.com.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. slee@hi.umn.edu.
authors.forename: Sung-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Skin Research Institute, Amorepacific Corporation R&D Center, Yongin 446-829, Korea. superbody@amorepacific.com.
authors.forename: Jun Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Skin Research Institute, Amorepacific Corporation R&D Center, Yongin 446-829, Korea. mhyeom@amorepacific.com.
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Yeom
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. hchen@hi.umn.edu.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. bodex008@umn.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. zgdong@hi.umn.edu.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Korea. kiwon@snu.ac.kr.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C502164:6,7,4'-trihydroxyisoflavone; D007529:Isoflavones; C004742:daidzein; D003094:Collagen; D051571:Protein Kinase C-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1