金雀异黄素减小瑞士韦伯斯特小鼠基底的肝细胞色素 P450 1A1 蛋白表达及活性_弗朗塞纳

针对病种：肝癌

发表时间：2016年

发表国家：美国

登载刊物：营养研究

研究单位：营养部和研究生组在营养生物学，加利福尼亚大学，戴维斯，戴维斯，CA 95616，美国

研究人员：弗朗塞纳斯坦伯格，伊瑞可佛朗伊恩

主要结论：本研究表明,染料木黄酮消耗减少本构肝Cyp1a1蛋白质表达和活动,从而有助于了解大豆异黄酮苷配基的调节细胞色素P450酶生物转化.

Nutrition Research, 2016, 36(5):430-439.

Genistein decreases basal hepatic cytochrome P450 1A1 protein expression and activity in Swiss Webster mice

Erik Froyen, Francene M. Steinberg

Department of Nutrition and Graduate Group in Nutritional Biology, University of California, Davis, Davis, CA 95616, USA

Soy consumption has been associated with risk reduction for chronic diseases such as cancer. One proposed mechanism for cancer prevention by soy is through decreasing cytochrome P450 1A1 (Cyp1a1) activity. However, it is not known with certainty which soy components modulate Cyp1a1, or the characteristics or mechanisms involved in the responses after short-term (<20 days) dietary treatment without concomitant carcinogen-mediated induction. Therefore, the objective was to test the hypothesis that physiologic concentrations of dietary genistein and/or daidzein will decrease basal hepatic Cyp1a1 protein expression and activity in male and female Swiss Webster mice via inhibiting the bindings of aryl hydrocarbon receptor (AhR)-AhR nuclear translocator (ARNT) and estrogen receptor-α to the Cyp1a1 promoter region xenobiotic response element. The mice were fed the AIN-93G diet supplemented with 1500 mg/kg of genistein or daidzein for up to 1 week. Genistein, but not daidzein, significantly decreased basal hepatic microsomal Cyp1a1 protein expression and activity. AhR protein expression was not altered. Molecular mechanisms were investigated in Hepa-1c1c7 cells treated with 5 μmol/L purified aglycones genistein, daidzein, or equol. Cells treated with genistein exhibited inhibitions in ARNT and estrogen receptor-α bindings to the Cyp1a1 promoter region. This study demonstrated that genistein consumption reduced constitutive hepatic Cyp1a1 protein expression and activity, thereby contributing to the understanding of how soy isoflavone aglycones modulate cytochrome P450 biotransformation enzymes.

美国《营养研究》, 2016, 36(5):430-439.

金雀异黄素减小瑞士韦伯斯特小鼠基底的肝细胞色素 P450 1A1 蛋白表达及活性

弗朗塞纳 · 斯坦伯格 Erik Froyen

营养部和研究生组在营养生物学，加利福尼亚大学，戴维斯，戴维斯，CA 95616，美国

食用大豆相关的慢性疾病如癌症的风险减少。一个提出癌症预防由大豆的机制是通过降低细胞色素 P450 1A1 (Cyp1a1) 活动。然而，并不可知是大豆哪个成分调节Cyp1a1，特征或机制参与反应的短期(< 20天)饮食治疗后没有伴随致癌物质介导感应的饮食治疗。因此，目的是测试膳食染料木黄酮和/或黄豆苷原的生理浓度将通过抑制芳烃受体（AhR）-AhR核转运蛋白的结合而降低雄性和雌性瑞士韦伯斯特小鼠中基底肝Cyp1a1蛋白表达和活性的假说（ARNT）和雌激素受体α到Cyp1a1启动子区域异源生物反应元件。老鼠AIN-93G的饮食补充1500毫克/公斤的染料木素和大豆苷1周。大豆苷、染料木素,但不显著降低基底肝微粒体Cyp1a1蛋白表达和活动。AhR蛋白表达并没有改变。Hepa-1c1c7细胞分子机制进行调查处理5μmol / L纯化苷配基染料木素、大豆苷或equol。细胞对染料木黄酮表现出抑制ARNT Cyp1a1启动子区域和雌激素receptor-α绑定。本研究表明,染料木黄酮消耗减少本构肝Cyp1a1蛋白质表达和活动,从而有助于了解大豆异黄酮苷配基的调节细胞色素P450酶生物转化。