首页> 外文期刊>Life sciences >Induction of apoptosis by Meretrix lusoria through reactive oxygen species production, glutathione depletion, and caspase activation in human leukemia cells.
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Induction of apoptosis by Meretrix lusoria through reactive oxygen species production, glutathione depletion, and caspase activation in human leukemia cells.

机译:Meretrix lusoria通过产生活性氧,谷胱甘肽耗竭和人白血病细胞中的半胱天冬酶活化来诱导凋亡。

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Apoptosis-induced directed fractionation and purification was used to identify the bioactive components of hard clams (HC), Meretrix lusoria. Two stereoisomers of epidioxysterol were previously identified as the active compounds in the ethyl acetate fraction (HC-EA). The molecular mechanism of HC-EA-induced apoptosis was also investigated in this study. Dissipation of mitochondrial membrane potential, release of mitochondrial cytochrome c into cytosol, and subsequent induction of pro-caspase-9 and -3 processing preceded apoptosis in HL-60 cells, confirmed by DNA fragmentation, chromatin condensation, changes in the cell membrane and the appearance of a sub-G1 DNA peak. Furthermore, treatment with HC-EA caused a rapid loss of intracellular glutathione content and stimulation of reactive oxygen species (ROS). Antioxidants such as catalase, N-acetylcysteine, pyrrolidine dithiocarbamate, and superoxide dismutase, but not allopurinol and diphenylene iodonium, significantly inhibited HC-EA-induced cell death. Apoptosis was completely prevented by a pan-caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK). The induction of apoptosis by M. lusoria may prove to be a pivotal mechanism for its cancer chemopreventive action.
机译:使用细胞凋亡诱导的定向分馏和纯化来鉴定硬蛤(Meretrix lusoria)的生物活性成分。先前已鉴定了环氧乙烷固醇的两种立体异构体为乙酸乙酯馏分(HC-EA)中的活性化合物。 HC-EA诱导细胞凋亡的分子机制也进行了研究。线粒体膜电位的耗散,线粒体细胞色素c的释放到细胞质中,随后诱导caspase-9和-3的过程先于HL-60细胞凋亡,这一过程已通过DNA片段化,染色质浓缩,细胞膜和细胞膜的改变得以证实。亚G1 DNA峰的外观。此外,用HC-EA进行治疗会引起细胞内谷胱甘肽含量的快速损失并刺激活性氧(ROS)。抗氧化剂,例如过氧化氢酶,N-乙酰半胱氨酸,吡咯烷二硫代氨基甲酸酯和超氧化物歧化酶,而不是别嘌醇和二亚苯基碘鎓,可显着抑制HC-EA诱导的细胞死亡。泛半胱天冬酶抑制剂z-Val-Ala-Asp-氟甲基酮(z-VAD-FMK)完全防止了细胞凋亡。支气管炎支原体诱导的细胞凋亡可能被证明是其化学预防作用的关键机制。

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