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首页> 外文期刊>Apoptosis: An international journal on programmed cell death >Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis
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Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis

机译:抑制半胱天冬酶依赖性线粒体通透性转变可保护气道上皮细胞免受芥子油诱导的凋亡

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摘要

In the present study, the toxicity of yperite, SM, and its structural analogue mechlorethamine, HN2, was investigated in a human bronchial epithelial cell line 16HBE. Cell detachment was initiated by caspase-2 activation, down-regulation of Bcl-2 and loss of mitochondrial membrane potential. Only in detached cells, mustards induced apoptosis associated with increase in p53 expression, Bax activation, decrease in Bcl-2 expression, opening of the mitochondrial permeability transition pore, release of cytochrome c, caspase-2, -3, -8, -9 and -13 activation and DNA fragmentation. Apoptosis, occurring only in detached cells, could be recognized as anoikis and the mitochondrion, involved both in cell detachment and subsequent cell death, appears to be a crucial checkpoint. Based on our understanding of the apoptotic pathway triggered by mustards, we demonstrated that inhibition of the mitochondrial pathway by ebselen, melatonin and cyclosporine A markedly prevented mustard-induced anoikis, pointing to these drugs as interesting candidates for the treatment of mustard-induced airway epithelial lesions.
机译:在本研究中,在人支气管上皮细胞系16HBE中研究了亚铁盐SM及其结构类似物甲氧乙胺HN2的毒性。通过caspase-2激活,Bcl-2的下调和线粒体膜电位的丧失来引发细胞脱离。芥子仅在分离的细胞中诱导凋亡,与p53表达增加,Bax激活,Bcl-2表达减少,线粒体通透性过渡孔打开,细胞色素c,caspase-2,-3,-8,-9释放有关和-13激活和DNA片段化。仅在分离的细胞中发生的细胞凋亡可以被认为是神经衰弱,而参与细胞分离和随后细胞死亡的线粒体似乎是关键的检查点。基于我们对芥子气触发的凋亡途径的了解,我们证明依布硒啉,褪黑激素和环孢素A对线粒体途径的抑制作用可显着预防芥子气诱导的神经衰弱,指出这些药物是治疗芥子气诱导的气道上皮的有趣候选药物病变。

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