國家衛生研究院 NHRI:Item 3990099045/6675
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    题名: Flavone regulation of steroidogenic CYP11B1 and CYP11B2 genes
    作者: Cheng, LC;Lin, JR;Li, LA
    贡献者: Division of Environmental Health and Occupational Medicine
    摘要: Recent years there are growing interests in flavonoids, a group of polyphenolic compounds present abundantly in plants, because of their pharmacological potential in anti-inflammation, antioxidation, anticancer and (anti-)estrogenicity. In a previous study, we found that 3′,4′-dimethoxyflavone (3′,4′-DMF) significantly increased CYP11B1 and CYP11B2 mRNA accumulation in human adrenocortical H295R cells. CYP11B1 and CYP11B2 are indispensable steroidogenic genes in charge of the final key steps of cortisol and aldosterone synthesis, respectively. In order to evaluate the benefits and risks of flavones in modulation of corticosteroid levels, we examined the effects of several flavones on CYP11B1 and CYP11B2 gene expression and associated steroidogenesis. All synthetic flavones examined increased expression of both genes dose dependently, but none of natural flavones examined did. CYP11B1 induction appeared 2 h after flavone stimulation and reached plateau between 10 and 24 h of treatment. Cortisol synthesis catalyzed by CYP11B1 increased following gene induction but with a time lag. Deletion analysis revealed that the Ad5 elements situated in the proximal promoters of CYP11B1 and CYP11B2 were responsible for flavone induction. Mutating the sequence of Ad5 abolished the response of CYP11B1 to 3′,4′-DMF. However, electrophoretic mobility shift assays showed little difference in DNA–protein association at the Ad5 site between 3′,4′-DMF treatment and vehicle control, suggesting that flavone treatment might alter the phosphorylation status rather than the DNA binding ability of the Ad5 binding protein(s). Although PD98059, a flavone-type MEK inhibitor, stimulated CYP11B1 and CYP11B2 promoter activation, the MAPK/ERK pathway was likely not involved because the nonflavone-type inhibitor U0126 exhibited an opposite effect.
    日期: 2010-07
    關聯: Toxicology Letters. 2010 Jul;196(Suppl.):S57-S58.
    Link to: http://dx.doi.org/10.1016/j.toxlet.2010.03.226
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0378-4274&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000208471300175
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