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20-O-β-d-Glucopyranosyl-20(S)-Protopanaxadiol Suppresses UV-Induced MMP-1 Expression Through AMPK-Mediated mTOR Inhibition as a Downstream of the PKA-LKB1 Pathway

Authors

  • Dong Joo Shin,

    1. WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea
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  • Jong-Eun Kim,

    1. Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea
    2. The Hormel Institute, University of Minnesota, Austin, Minnesota
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  • Tae-Gyu Lim,

    1. Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea
    2. The Hormel Institute, University of Minnesota, Austin, Minnesota
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  • Eun Hee Jeong,

    1. WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea
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  • Gaeun Park,

    1. WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea
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  • Nam Joo Kang,

    1. School of Food Science and Biotechnology, Kyungpook National University, Daegu, Republic of Korea
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  • Jun-Seong Park,

    1. Skin Research Institute, Amorepacific Corporation R&D Center, Yongin, Korea
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  • Myeong-Hun Yeom,

    1. Skin Research Institute, Amorepacific Corporation R&D Center, Yongin, Korea
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  • Deok Kun Oh,

    1. Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea
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  • Ann M. Bode,

    1. The Hormel Institute, University of Minnesota, Austin, Minnesota
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  • Zigang Dong,

    1. The Hormel Institute, University of Minnesota, Austin, Minnesota
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  • Hyong Joo Lee,

    Corresponding author
    1. Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea
    • Correspondence to: Hyong Joo Lee, Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang 232-916, Republic of Korea.

      E-mail: leehyjo@snu.ac.kr

      **Correspondence to: Ki Won Lee, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.

      E-mail: kiwon@snu.ac.kr

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  • Ki Won Lee

    1. WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea
    2. Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea
    3. Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea
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  • Dong Joo Shin, Jong-Eun Kim, and Tae-Gyu Lim contributed equally to this study.

ABSTRACT

Various health effects have been attributed to the ginsenoside metabolite 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD); however, its effect on ultraviolet (UV)-induced matrix metalloproteinase (MMP)-1 expression and the mechanism underlying this effect are unknown. We examined the inhibitory effect of GPD on UV-induced MMP-1 expression and its mechanisms in human dermal fibroblasts (HDFs). GPD attenuated UV-induced MMP-1 expression in HDFs and suppressed the UV-induced phosphorylation of mammalian target of rapamycin (mTOR) and p70S6K without inhibiting the activity of phosphatidylinositol 3-kinase and Akt, which are well-known upstream kinases of mTOR. GPD augmented the phosphorylation of liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK), which are inhibitors of mTOR, to a greater extent than UV treatment alone. Similar to GPD, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5′-monophosphate (AICAR), an activator of AMPK, augmented UV-induced AMPK phosphorylation to a greater extent than UV treatment alone, resulting in the inhibition of MMP-1 expression. AICAR also decreased the phosphorylation of mTOR and p70S6K. However, compound C, an antagonist of AMPK, increased MMP-1 expression. In HDF cells with AMPK knock-down using shRNA, MMP-1 expression was increased. These results indicate that AMPK activation plays a key role in MMP-1 suppression. Additionally, the cAMP-dependent protein kinase (PKA) inhibitor, H-89, antagonized GPD-mediated MMP-1 suppression via the inhibition of LKB1. Our results suggest that the suppressive activity of GPD on UV-induced MMP-1 expression is due to the activation of AMPK as a downstream of the PKA-LKB1 pathway. J. Cell. Biochem. 115: 1702–1711, 2014. © 2014 Wiley Periodicals, Inc.

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