Ascorbic acid promotes detoxification and elimination of 4-hydroxy-2(E)-nonenal in human monocytic THP-1 cells.
Ascorbic acid promotes detoxification and elimination of 4-hydroxy-2(E)-nonenal in human monocytic THP-1 cells.
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DOI：
10.1021/tx900042u
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发表时间：
2009-05
影响因子：
4.1
通讯作者：
Stevens, Jan F.
中科院分区：
文献类型：
--
作者：
Miranda, Cristobal L.;Reed, Ralph L.;Kuiper, Heather C.;Alber, Susan;Stevens, Jan F.
4-羟基-2(E)-壬烯醛(HNE)是一种源于氧化脂质的反应性醛，它与心血管和神经系统疾病的发病机制有关，部分原因是它能够诱导氧化应激和靶细胞中的蛋白质羰化。研究了细胞内抗坏血酸(维生素C)对HNE诱导的人THP-1单核细胞系细胞毒作用和蛋白质羰化作用的影响。经HNE处理后，这些细胞发生凋亡、坏死和蛋白质羰化。0.1 mM或1 mM抗坏血酸处理细胞18h后，6.4 mM或8.9 mM的抗坏血酸在细胞内积累，1.0 mM的抗坏血酸可抑制HNE诱导的细胞内活性氧的形成和蛋白质羰基的形成。抗坏血酸的保护作用与LC-MS/MS测定的GSH-HNE结合物及其1相代谢物的形成增加和GSH结合物从细胞到培养液的转运增加有关。抗坏血酸可促进多药耐药蛋白(MRP)底物--羧基-2‘，7’-二氯荧光素(CDF)的外流，并阻断HNE对THP-1细胞CDF输出的抑制作用，提示抗坏血酸对HNE细胞毒性的保护作用是通过调节MRP介导的GSH-HNE结合代谢产物的转运实现的。在细胞暴露实验中观察到HNE的抗坏血酸加合物的形成，但它代表了一条有助于消除HNE和抗坏血酸保护作用的次要途径。
4-Hydroxy-2(E)-nonenal (HNE), a reactive aldehyde derived from oxidized lipids, has been implicated in the pathogenesis of cardiovascular and neurological diseases, in part by its ability to induce oxidative stress and by protein carbonylation in target cells. The effects of intracellular ascorbic acid (vitamin C) on HNE-induced cytotoxicity and protein carbonylation were investigated in human THP-1 monocytic leukemia cells. HNE treatment of these cells resulted in apoptosis, necrosis and protein carbonylation. Ascorbic acid accumulated in the cells at concentrations of 6.4 mM or 8.9 mM after treatment with 0.1 mM or 1 mM ascorbate in the medium for 18 h. Pretreatment of cells with 1.0 mM ascorbate decreased HNE-induced formation of reactive oxygen species and formation of protein carbonyls. The protective effects of ascorbate were associated with an increase of the formation of GSH-HNE conjugate and its phase-1 metabolites, measured by LC-MS/MS, and with increased transport of GSH conjugates from the cells into the medium. Ascorbate pretreatment enhanced the efflux of the multidrug resistant protein (MRP) substrate, carboxy-2',7'-dichlorofluorescein (CDF), and it prevented the HNE-induced inhibition of CDF export from THP-1 cells, suggesting that the protective effect of ascorbate against HNE cytotoxicity is through modulation of MRP-mediated transport of GSH-HNE conjugate metabolites. Formation of ascorbate adducts of HNE was observed in the cell exposure experiments, but it represented a minor pathway contributing to the elimination of HNE and to the protective effects of ascorbate.
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影响因子：
4.4
作者：
BREEUWER, P;DROCOURT, JL;ABEE, T
通讯作者：
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影响因子：
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作者：
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影响因子：
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2.9
作者：
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通讯作者：
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