Institute of Immunology, Faculty of Medicine, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074 Aachen, Germany.
Breast Cancer Molecular Pharmacology, Welsh School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3NB, United Kingdom.
J Nutr Biochem. 2019 Feb;64:72-79. doi: 10.1016/j.jnutbio.2018.10.008. Epub 2018 Oct 26.
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.
锌离子作为第二信使在主要的细胞途径中发挥作用，包括增殖的调节途径，其适当的调节对于维持内环境平衡和生物体的健康是必要的。因此，锌转运体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，用人疱疹病毒 4 型（EBV）感染 B 细胞以产生永生化细胞，这些细胞显示出肿瘤细胞的特征，如高增殖率和延长的寿命。这些细胞表现出锌转运体表达的差异改变，ZIP7 的 RNA 和蛋白表达特别增加，以及 EBV 转化的 B 细胞中 ZIP7 的相应磷酸化增加。因此，这些细胞内的游离锌水平升高。为了证明观察到的变化是由于永生化还是高增殖引起的，测定了体外激活的 B 细胞中和表达激活标志物 CD69 的新鲜分离的 B 细胞中的游离锌水平。这里发现比较高的锌水平，提示激活和增殖，而不是永生化，是细胞内游离锌升高的关键因素。
