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首页> 外文期刊>The Journal of toxicological sciences >The effect of dihydropyrazines on human hepatoma HepG2 cells: a comparative study using 2,3-dihydro-5,6-dimethylpyrazine and 3-hydro-2,2,5,6-tetramethylpyrazine
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The effect of dihydropyrazines on human hepatoma HepG2 cells: a comparative study using 2,3-dihydro-5,6-dimethylpyrazine and 3-hydro-2,2,5,6-tetramethylpyrazine

机译：二氢吡嗪对人肝癌Hepg2细胞的影响：使用2,3-二氢-5,6-二甲基吡嗪和3-氢-2,2,5,6-四甲基吡嗪的对比研究

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Dihydropyrazines (DHPs) are glycation products that are nonenzymatically generated in vivo and in food. In this study, we compared the effects of 2,3-dihydro-5,6-dimethylpyrazine (DHP-1), a low toxicity DHP, and 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), a high toxicity DHP on the redox indices in HepG2 cells. An apparent increase in intracellular hydrogen peroxide concentration was observed at 24 hr after 1 mM DHP-3 treatment. In addition, DHP-3 exposure significantly increased the mRNA levels of heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit (GCLC), which are stress-responsive genes, at 6 hr (HO-1 and GCLC), 12 hr (HO-1 and GCLC) and 24 hr (GCLC) after exposure. These indices, with the exception of the increase in GCLC mRNA after a 6 hr exposure, were not affected by treatment with 1 mM DHP-1. HO-1, GCLC, and nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels also increased at 6 hr (Nrf2), 12 hr (Nrf2, HO-1 and GCLC) and 24 hr (GCLC) after DHP-3 treatment. The increase in HO-1 and Nrf2 protein levels were observed with lower concentration (0.5 mM) of DHP-3, and in agreement with this, antioxidant responsive element-luciferase reporter activity was significantly increased with exposure to at least 0.5 mM DHP-3. These results support our previous report establishing that oxidative stress is in part involved in the effects of DHP on mammalian cells. Additionally, our results suggest that the cell response to DHP-3 exposure was exerted via the activation of the Nrf2-ARE signal pathway.
机译：二氢吡嗪（DHPS）是在体内和食物中非酶促产生的糖基产物。在该研究中，我们将2,3-二氢-5,6-二甲基吡嗪（DHP-1），低毒性DHP和3-HYDRO-2,2,5,6-四甲基吡嗪（DHP-3）的影响进行了比较了效果，HepG2细胞中氧化还原索引的高毒性DHP。在1mM DHP-3处理后24小时观察到细胞内过氧化氢浓度的表观增加。此外，DHP-3暴露显着增加了血红素氧酶-1（HO-1）和谷氨酸半胱氨酸连接酶催化亚基（GCLC）的mRNA水平，其是应激反应基因，6小时（HO-1和GCLC），暴露后12小时（HO-1和GCLC）和24小时（GCLC）。这些指数除了6小时暴露后GCLC mRNA的增加，不受1mM DHP-1治疗的影响。 HO-1，GCLC和核因子红外2相关因子2（NRF2）蛋白质水平在DHP-3之后，在6小时（NRF2），12小时（NRF2，HO-1和GCLC）和24小时（GCLC）中也增加了24小时治疗。观察到HO-1和NRF2蛋白水平的增加，用较低浓度（0.5mm）的DHP-3，并且在此方面，抗氧化剂响应元素 - 荧光素酶报告活性随着暴露于至少0.5 mm DHP-3而显着增加。这些结果支持我们之前的报告，建立氧化应激部分参与DHP对哺乳动物细胞的影响。另外，我们的结果表明通过NRF2的激活来施加对DHP-3暴露的细胞响应 - 是信号途径。

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