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Int. J. Mol. Sci. 2014, 15(11), 21419-21432; doi:10.3390/ijms151121419

The Daidzein Metabolite, 6,7,4'-Trihydroxyisoflavone, Is a Novel Inhibitor of PKCα in Suppressing Solar UV-Induced Matrix Metalloproteinase 1

1
World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Korea
2
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
3
Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Korea
4
Skin Research Institute, Amorepacific Corporation R&D Center, Yongin 446-829, Korea
5
Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang 232-916, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 10 September 2014 / Revised: 31 October 2014 / Accepted: 4 November 2014 / Published: 19 November 2014
(This article belongs to the Collection Radiation Toxicity in Cells)
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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. View Full-Text
Keywords: matrix metalloproteinase 1; protein kinase C (PKC)α; photoaging; 6,7,4'-trihydroxyisoflavone matrix metalloproteinase 1; protein kinase C (PKC)α; photoaging; 6,7,4'-trihydroxyisoflavone
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lim, T.-G.; Kim, J.-E.; Lee, S.-Y.; Park, J.S.; Yeom, M.H.; Chen, H.; Bode, A.M.; Dong, Z.; Lee, K.W. The Daidzein Metabolite, 6,7,4'-Trihydroxyisoflavone, Is a Novel Inhibitor of PKCα in Suppressing Solar UV-Induced Matrix Metalloproteinase 1. Int. J. Mol. Sci. 2014, 15, 21419-21432.

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