B cell activation and proliferation increase intracellular zinc levels
B cell activation and proliferation increase intracellular zinc levels
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DOI：
10.1016/j.jnutbio.2018.10.008
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发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Rink, Lothar
中科院分区：
文献类型：
--
作者：
Ollig, Johanna;Kloubert, Veronika;Rink, Lothar
锌离子作为第二信使在主要的细胞途径，包括增殖的调节途径，其适当的调节是必要的稳态和健康的有机体。因此，锌转运蛋白的表达可以在各种癌细胞系中改变，并且通常涉及产生升高的细胞内锌水平。在这项研究中，人类B细胞被EB病毒（EBV）感染，产生永生化细胞，这揭示了肿瘤细胞的特征，如高增殖率和延长的寿命。这些细胞显示出差异改变的锌转运蛋白表达，其中ZIP 7 RNA和蛋白质表达尤其增加，以及在EBV转化的B细胞中ZIP 7的相应增加的磷酸化。因此，这些细胞内的游离锌水平升高。为了证明所观察到的变化是由永生化还是相当高的增殖引起的，测定了体外活化的B细胞和表达活化标志物CD 69的新鲜分离的B细胞中的游离锌水平。在这里，相对增加的锌水平被发现，这表明，激活和增殖，但不是永生化，作为细胞内游离锌升高的关键因素。(C)2018作者爱思唯尔公司出版
Zinc ions serve as second messengers in major cellular pathways, including the regulation pathways of proliferation and their proper regulation is necessary for homeostasis and a healthy organism. Accordingly, expression of zinc transporters can be altered in various cancer cell lines and is often involved in producing elevated intracellular zinc levels. In this study, human B cells were infected with Epstein-Barr virus (EBV) to generate immortalized cells, which revealed traits of tumor cells, such as high proliferation rates and an extended lifespan. These cells showed differentially altered zinc transporter expression with ZIP7 RNA and protein expression being especially increased as well as a corresponding increased phosphorylation of ZIP7 in EBV-transformed B cells. Accordingly, free zinc levels were elevated within these cells. To prove whether the observed changes resulted from immortalization or rather high proliferation, free zinc levels in in vitro activated B cells and in freshly isolated B cells expressing the activation marker CD69 were determined. Here, comparatively increased zinc levels were found, suggesting that activation and proliferation, but not immortalization, act as crucial factors for the elevation of intracellular free zinc. (C) 2018 The Authors. Published by Elsevier Inc.