AMPK synergizes with the combined treatment of 1'-acetoxychavicol acetate and sodium butyrate to upregulate phase II detoxifying enzyme activities.
AMPK synergizes with the combined treatment of 1'-acetoxychavicol acetate and sodium butyrate to upregulate phase II detoxifying enzyme activities.
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DOI：
10.1002/mnfr.201200809
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发表时间：
2013-07
影响因子：
5.2
通讯作者：
Keisuke Yaku;I. Matsui‐yuasa;Y. Konishi;A. Kojima‐Yuasa
中科院分区：
文献类型：
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作者：
Keisuke Yaku;I. Matsui‐yuasa;Y. Konishi;A. Kojima‐Yuasa
SCOPE II相酶在解毒外源性物质中发挥重要作用。我们以前报道过，1 '-乙酰氧基胡椒酚乙酸酯（ACA）和丁酸钠单独增加II相酶的活性。在这里，我们确定了ACA和丁酸钠对肠上皮细胞（IEC 6）中II相酶活性的联合作用。方法和结果ACA和丁酸钠协同增加II相酶活性。ACA或丁酸钠处理可增加核内转录因子NF-E2相关因子2（NRF 2）的蛋白水平，但两者处理均未产生协同效应。核内p53蛋白水平增加ACA，但丁酸钠单独或与ACA和丁酸钠联合治疗降低。相反，p53乙酰化促进丁酸钠和ACA和丁酸钠的组合。AMPK活性的抑制降低了II相酶活性，这些酶活性通过ACA加丁酸钠或其他植物化学物质（包括山奈酚、槲皮素和表没食子儿茶素-3-没食子酸酯）的处理而上调。ACA和丁酸钠联合治疗增加磷酸化AMPK水平。结论ACA和丁酸钠协同促进外源性物质的代谢。ACA和丁酸钠联合治疗通过AMPK活化和p53乙酰化协同上调II期酶活性。
SCOPE Phase II enzymes play important roles in detoxifying xenobiotics. We previously reported that both 1'-acetoxychavicol acetate (ACA) and sodium butyrate individually increased phase II enzyme activities. Here, we determined the combined action of ACA and sodium butyrate on phase II enzyme activities in intestinal epithelial cells (IEC 6). METHODS AND RESULTS ACA and sodium butyrate synergistically increased phase II enzyme activities. Protein levels of intranuclear transcription factor NF-E2-related factor 2 (Nrf2) were increased by ACA or sodium butyrate treatment, but treatment with both did not produce a synergistic effect. Intranuclear p53 protein levels were increased by ACA but decreased by sodium butyrate alone or combined treatment with ACA and sodium butyrate. In contrast, p53 acetylation was promoted by sodium butyrate and the ACA and sodium butyrate combination. Inhibition of AMPK activity decreased phase II enzyme activities that were upregulated by treatment with ACA plus sodium butyrate or other phytochemicals, including kaempferol, quercetin, and epigallocatechin-3-gallate. Combined treatment with ACA and sodium butyrate increased phosphorylated AMPK levels. CONCLUSION These results suggest that ACA and sodium butyrate synergistically contribute to xenobiotics metabolism. The combined ACA and sodium butyrate treatment synergistically upregulated phase II enzyme activities through AMPK activation and p53 acetylation.