MDR1 is Related to Intestinal Epithelial Injury Induced by Acetylsalicylic Acid
MDR1 is Related to Intestinal Epithelial Injury Induced by Acetylsalicylic Acid
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DOI：
10.1159/000354497
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Itoh, Yoshito
中科院分区：
文献类型：
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作者：
Kugai, Munehiro;Uchiyama, Kazuhiko;Itoh, Yoshito
背景/目标：虽然阿司匹林对肠上皮细胞的细胞毒性是一个主要的临床问题，但对其发病机制知之甚少。我们使用多药耐药（MDR）1基因转染的Caco 2细胞评估了多药耐药（MDR）1在阿司匹林引起的肠上皮细胞损伤中的作用。方法：用不同浓度的阿司匹林处理Caco 2细胞24 h。用维拉帕米（一种MDR 1的特异性抑制剂）处理Caco 2细胞后，我们在阿司匹林刺激后24小时使用WST-8测定法评估细胞损伤的程度。我们在MDR 1基因转染的Caco 2细胞中进行了相同的程序。为了确定MDR 1在阿司匹林代谢中的作用，使用AC标记的阿司匹林进行流量研究。结果如下：阿司匹林诱导的细胞损伤水平在维拉帕米处理的Caco 2细胞中高于对照细胞，并且在MDR 1转染的Caco 2细胞中不那么严重。维拉帕米处理的Caco 2细胞中，4C标记的阿司匹林的外排高于对照细胞。结论：这些数据表明，阿司匹林外排发生通过MDR 1转运蛋白和MDR 1转运蛋白参与阿司匹林诱导的细胞损伤的发病机制。版权所有（C）2013 S. Karger AG，巴塞尔
Background/Aims: Although the cytotoxicity of aspirin against the intestinal epithelium is a major clinical problem, little is known about its pathogenesis. We assessed the involvement of Multi Drug Resistance (MDR) 1 in intestinal epithelial cell injury caused by aspirin using MDR1 gene-transfected Caco2 cells. Methods: Caco2 cells were treated with various concentrations of aspirin for 24 h. After treatment of Caco2 cells with verapamil, a specific inhibitor of MDR1, we assessed the extent of cell injury using a WST-8 assay at 24 h after aspirin-stimulation. We performed the same procedure in MDR1 gene-transfected Caco2 cells. To determine the function of MDR1 in the metabolism of aspirin, flux study was performed using 'AC-labeled aspirin. Results: The level of aspirin-induced cell injury was higher in verapamil-treated Caco2 cells than in control cells and was less serious in MDR1-transfected Caco2 cells than in control vector-transfected cells. The efflux of '4C-labeled aspirin was higher in verapamil-treated Caco2 cells than in control cells. Conclusion: These data suggest that aspirin efflux occurs through the MDR1 transporter and that the MDR1 transporter is involved in the pathogenesis of aspirin-induced cell injury. Copyright (C) 2013 S. Karger AG, Basel