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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells.
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Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells.

机译:柳氮磺胺吡啶诱导的Raw 264.7细胞死亡中,ROS的产生和神经酰胺的产生离解。

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Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.
机译:柳氮磺吡啶(SSZ)是一种用于炎症性肠病的药物,其确切的作用机理尚待阐明。在这里,我们报告与SSZ,而不是水杨酸盐[乙酰水杨酸(ASA),4-氨基水杨酸(4-ASA)和5-ASA]的Raw 264.7细胞孵育会导致细胞凋亡和坏死细胞混合死亡。与之代谢产物磺胺吡啶和5-ASA相比,未加工的264.7细胞中的SSZ暴露导致神经酰胺生成增加了三倍,并且产生了活性氧(ROS)。但是,伏马毒素B1对神经酰胺产生的抑制作用不能减弱细胞死亡。与过氧化氢酶,环孢菌素A(CsA)和邦克里奇酸的预温育可降低ROS的产生。当定量死细胞的凋亡与坏死细胞的数量时,过氧化氢酶和N-乙酰半胱氨酸可再现地减弱细胞凋亡,而观察到的CsA除了减少细胞凋亡外,还显着增强了坏死。总之,由SSZ诱导的Raw 264.7细胞中的细胞死亡反应涉及凋亡肢体中的ROS,但与神经酰胺的形成无关。

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