7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways

  • Authors:
    • Min Ju Ryu
    • Kyoung Ah Kang
    • Mei Jing Piao
    • Ki Cheon Kim
    • Jian Zheng
    • Cheng Wen Yao
    • Ji Won Cha
    • Ha Sook Chung
    • Sang Cheol Kim
    • Eunsun Jung
    • Deokhoon Park
    • Sungwook Chae
    • Jin Won Hyun
  • View Affiliations

  • Published online on: February 4, 2014     https://doi.org/10.3892/ijmm.2014.1643
  • Pages: 964-970
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Abstract

This study investigated the effect of 7,8-dihydroxyflavone (DHF) on the expression and activity of heme oxygenase-1 (HO-1), an enzyme with potent antioxidant properties, as well as the molecular mechanisms involved. DHF markedly upregulated HO-1 mRNA and protein expression in human keratinocytes (HaCaT cells), resulting in increased HO-1 activity. DHF also increased the protein level of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates HO-1 expression by binding to the antioxidant response element (ARE) within the HO-1 gene promoter, in a time‑dependent manner. Moreover, DHF decreased the expression of Kelch-like ECH-associated protein 1, a repressor of Nrf2 activity, and induced the translocation of Nrf2 from the cytosol into the nucleus, thereby allowing its association with the ARE site. DHF activated extracellular-regulated kinase (ERK) and protein kinase B (PKB, Akt) in keratinocytes, while the ERK and Akt inhibitors attenuated DHF-enhanced Nrf2 and HO-1 expression. DHF also protected the keratinocytes against hydrogen peroxide- and ultraviolet B-induced oxidative damage, while HO-1, ERK and Akt inhibitors markedly suppressed DHF-mediated cytoprotection. Taken together, the results suggested that DHF activates ERK- and Akt-Nrf2 signaling cascades in HaCaT cells, leading to the upregulation of HO-1 and cytoprotection against oxidative stress.
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2014-April
Volume 33 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Ryu MJ, Kang KA, Piao MJ, Kim KC, Zheng J, Yao CW, Cha JW, Chung HS, Kim SC, Jung E, Jung E, et al: 7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. Int J Mol Med 33: 964-970, 2014
APA
Ryu, M.J., Kang, K.A., Piao, M.J., Kim, K.C., Zheng, J., Yao, C.W. ... Hyun, J.W. (2014). 7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. International Journal of Molecular Medicine, 33, 964-970. https://doi.org/10.3892/ijmm.2014.1643
MLA
Ryu, M. J., Kang, K. A., Piao, M. J., Kim, K. C., Zheng, J., Yao, C. W., Cha, J. W., Chung, H. S., Kim, S. C., Jung, E., Park, D., Chae, S., Hyun, J. W."7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways". International Journal of Molecular Medicine 33.4 (2014): 964-970.
Chicago
Ryu, M. J., Kang, K. A., Piao, M. J., Kim, K. C., Zheng, J., Yao, C. W., Cha, J. W., Chung, H. S., Kim, S. C., Jung, E., Park, D., Chae, S., Hyun, J. W."7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways". International Journal of Molecular Medicine 33, no. 4 (2014): 964-970. https://doi.org/10.3892/ijmm.2014.1643