Title

Naringenin Targets ERK2 and Suppresses UVB-Induced Photoaging

Authors

S. K. Jung, The Hormel Institute, University of Minnesota
S. J. Ha, Division of Functional Food Research, Korea Food Research Institute, Seongnam, South Korea
C. H. Jung, Division of Functional Food Research, Korea Food Research Institute, Seongnam, South Korea
Y. T. Kim, Division of Functional Food Research, Korea Food Research Institute, Seongnam, South Korea
M. O. Kim, The Hormel Institute, University of Minnesota
M. H. Lee, The Hormel Institute, University of Minnesota
M Mottamal, The Hormel Institute, University of MinnesotaFollow
A. M. Bode, The Hormel Institute, University of Minnesota
K. W. Lee, WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, South Korea
Z. Dong, The Hormel Institute, University of Minnesota

Funding Source

Hormel Institute, National Institutes of Health, National Research Foundation (Republic of Korea)

Grant Number

CA120388, CA111536, CA077646, R37CA0810064, 2015R1A2A1A10053567

Department

Department of Chemistry

Document Type

Article

Publication Date

5-1-2016

Abstract

A number of natural phytochemicals have anti-photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase-1 (MMP-1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB-induced MMP-1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3-dimensional (3-D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm2) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB-induced MMP-1 expression and AP-1 activity, and strongly suppressed UVB-induced phosphorylation of Fos-related antigen (FRA)-1 at Ser265. Importantly, UVB irradiation-induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen-activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB-induced extracellular signal-regulated kinase 2 (ERK2) activity and subsequently attenuated UVB-induced phosphorylation of p90RSK by competitively binding with ATP. Constitutively active MEK (CA-MEK) increased FRA1 phosphorylation and expression and also induced MMP-1 expression, whereas dominant-negative ERK2 (DN-ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP-1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB-induced wrinkle formation, trans-epidermal water loss and MMP-13 expression. Naringenin exerts potent anti-photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down-regulation of AP-1 transactivation and MMP-1 expression.

Comments

DOI: 10.1111/jcmm.12780

PubMed ID: 26861188

Acknowledgement

Contract grant sponsor: The Hormel Foundation, National Institutes of Health grants CA120388, CA111536, CA077646, R37CA0810064; Leap Research Program through the National Research Foundation, Ministry of Science, ICT and Future Planning, Republic of Korea (2015R1A2A1A10053567) and a grant from the Korea Food Research Institute, Republic of Korea.

Recommended Citation

Jung, S. K.; Ha, S. J.; Jung, C. H.; Kim, Y. T.; Kim, M. O.; Lee, M. H.; Mottamal, M; Bode, A. M.; Lee, K. W.; and Dong, Z., "Naringenin Targets ERK2 and Suppresses UVB-Induced Photoaging" (2016). Faculty and Staff Publications. 153.
https://digitalcommons.xula.edu/fac_pub/153