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Vitamin A treatment induces apoptosis through an oxidant-dependent activation of the mitochondrial pathway

机译:维生素A治疗通过线粒体途径的氧化剂依赖性激活诱导凋亡

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摘要

Even though retinoids are widely used as adjuvant in chemotherapeutic interventions to improve cancer cell death, their mechanism(s) of action involves multiple overlapping pathways that remain unclear. We have previously shown that vitamin A, the natural precursor of the retinoids, induces oxidative-dependent cytochrome c release from isolated mitochondria, suggesting a putative mechanism for apoptosis activation. Using Sertoli cells in culture, we show that retinol causes mitochondrial-dependent apoptosis, involving oxidative stress. Apoptosis was evaluated by nuclear morphology, DNA fragmentation, and caspase-3/7 activity. Retinol induced oxidant- and time-dependent imbalance of several mitochondrial parameters, cytochrome c release and caspase-3/7 activation, leading cells to commit apoptosis. All parameters tested were attenuated or blocked by trolox co-administration, suggesting that retinol induces apoptosis through oxidative damage, which mitochondria plays a pivotal role.
机译:尽管类视黄醇广泛用作化疗干预措施的佐剂,以改善癌细胞死亡,但它们的作用机制涉及多种重叠途径,目前尚不清楚。我们先前已经表明,维生素A(类维生素A的天然前体)诱导了线粒体中氧化依赖性细胞色素C的释放,提示了凋亡激活的推测机制。使用文化中的支持细胞,我们表明视黄醇会导致线粒体依赖性细胞凋亡,涉及氧化应激。通过核形态,DNA片段化和caspase-3 / 7活性评估凋亡。视黄醇诱导多种线粒体参数,细胞色素c释放和caspase-3 / 7活化的氧化剂和时间依赖性失衡,导致细胞发生凋亡。通过trolox共同给药可减弱或阻断所有测试参数,表明视黄醇通过氧化损伤诱导细胞凋亡,而线粒体起着关键作用。

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