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首页> 外文期刊>Cellular Physiology and Biochemistry >Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells
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Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

机译：TPEN的锌耗竭诱导人类急性早幼粒细胞NB4细胞凋亡。

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>Background/Aims: The effects of zinc signaling on proliferation or apoptosis of leukemia cells remain elusive. In the present study, we used N, N, Na€?, Na€?-tetrakis-(2-pyridylmethyl)-ethylene-diamine (TPEN), a membrane-permeable zinc chelator, to evaluate the effect of zinc depletion on survival and apoptosis of NB4 acute promyelocytic leukemia (APL) cells. Methods: The pro-apoptotic effects of TPEN on NB4 cells were examined by flow cytometry, and observed using an optical microscope. Intracellular labile zinc, nitric oxide (NO) or reactive oxygen species (ROS) changes caused by TPEN were measured by flow cytometry. We then explored possible roles of the crosstalk between intracellular labile zinc signaling and nitric oxide signaling in TPEN-triggered apoptosis. Results: we found that TPEN induced apoptosis in NB4 APL cells in a dosage-dependent manner. We further demonstrated that TPEN triggered apoptosis by attenuating intracellular zinc and nitric oxide signaling in NB4 cells. Both exogenous zinc supplement and the nitric donor sodium nitroprusside (SNP) pre-incubation reversed TPEN-mediated inhibition of intracellular NO and Zn2+ signaling, and rescued NB4 cells from apoptosis. Conclusion: These results suggest for the first time that crosstalk between zinc signaling and nitric oxide pathway is essential for the survival of NB4 cells. TPEN induces apoptosis in NB4 cells via negatively regulating intracellular NO and Zn2+ signaling. Our in vitro data suggest that zinc depletion by TPEN may be a potential therapeutic strategy for APL.
机译：> 背景/目的： 锌信号对白血病细胞增殖或凋亡的影响仍然难以捉摸。在本研究中，我们使用膜渗透性锌螯合剂N，N，Na？，Na？-四-（2-吡啶基甲基）-乙二胺（TPEN）来评估锌耗竭对生存的影响NB4急性早幼粒细胞白血病（APL）细胞的凋亡和凋亡 方法： 用流式细胞仪检测TPEN对NB4细胞的促凋亡作用，并用光学显微镜观察。通过流式细胞仪测量TPEN引起的细胞内不稳定锌，一氧化氮（NO）或活性氧（ROS）的变化。然后，我们探讨了在TPEN触发的细胞凋亡中细胞内不稳定的锌信号传导和一氧化氮信号传导之间的串扰的可能作用。 结果： 我们发现TPEN以剂量依赖性方式诱导NB4 APL细胞凋亡。我们进一步证明，TPEN通过减弱NB4细胞中的细胞内锌和一氧化氮信号而触发凋亡。外源锌补充剂和硝酸供体硝普钠（SNP）的预培养均逆转了TPEN介导的对细胞内NO和Zn 2 + 信号转导的抑制作用，并使NB4细胞免于凋亡。 结论： 这些结果首次表明，锌信号传导与一氧化氮途径之间的串扰对于NB4细胞的生存至关重要。 TPEN通过负调控细胞内NO和Zn 2 + 信号转导诱导NB4细胞凋亡。我们的体外数据表明TPEN消耗锌可能是APL的潜在治疗策略。

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