title: Microarray and pathway analysis highlight Nrf2/ARE-mediated expression profiling by polyphenolic myricetin.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  An Nrf2-mediated ARE activation is involved in myricetin-induced expression profiling in hepatic cells.
authors.affiliation: Course of Biological Science and Technology, United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto, Kagoshima, Japan.
authors.forename: Si
authors.initials: S
authors.lastname: Qin
authors.forename: Jihua
authors.initials: J
authors.lastname: Chen
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanigawa
authors.forename: De-Xing
authors.initials: DX
authors.lastname: Hou
mesh_terms: D061745:Antioxidant Response Elements / Q000187:drug effects / Q000235:genetics*; D005419:Flavonoids / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; C040015:myricetin