Microarray and pathway analysis highlight Nrf2/ARE-mediated expression profiling by polyphenolic myricetin

Authors

  • Si Qin,

    1. Course of Biological Science and Technology, United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto, Kagoshima, Japan
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  • Jihua Chen,

    1. Course of Biological Science and Technology, United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto, Kagoshima, Japan
    Current affiliation:
    1. Xiangya School of Public Health, Central South University, Changsha, P. R.China
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  • Shunsuke Tanigawa,

    1. Course of Biological Science and Technology, United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto, Kagoshima, Japan
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  • De-Xing Hou

    Corresponding author
    1. Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, Kagoshima, Japan
    • Course of Biological Science and Technology, United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto, Kagoshima, Japan
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Correspondence: Professor De-Xing Hou, Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan

E-mail: hou@chem.agri.kagoshima-u.ac.jp

Fax: +81-99-285-8649.

Abstract

Scope

Myricetin is a dietary flavonol and widely distributed in many edible plants. It has been reported to have many bioactivities and considered as a promising chemopreventive compound. The present study aimed to investigate the influences of myricetin on gene expressions in genome-wide and underlying mechanisms.

Methods and results

Among total 44K gene probes, myricetin treatment upregulated the signals of 143 gene probes (0.33% of total probes) and downregulated signals of 476 gene probes (1.08% of total probes) by greater than or equal to twofold in HepG2 cells. The network pathway analysis revealed that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response element (ARE) activation is involved in myricetin-induced genes expressions. Molecular data revealed that myricetin activated Nrf2-ARE pathway by inhibiting Nrf2 ubiquitination and protein turnover, stimulating Nrf2 expression and kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 modification. All of these events finally increased nuclear Nrf2 accumulation and ARE-binding activity to enhance ARE-mediated genes expressions. Additionally, treatment with Nrf2 small interfering RNA attenuated the myricetin-induced ARE activity and gene expression.

Conclusion

An Nrf2-mediated ARE activation is involved in myricetin-induced expression profiling in hepatic cells.

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