College of Health and Medicine, School of Health Sciences, University of Tasmania, Newnham Campus, Launceston 7250, Australia.
Molecules. 2020 Nov 3;25(21):5098. doi: 10.3390/molecules25215098.
Zinc is an essential metal ion involved in many biological processes. Studies have shown that zinc can activate several molecules in the insulin signalling pathway and the concomitant uptake of glucose in skeletal muscle cells. However, there is limited information on other potential pathways that zinc can activate in skeletal muscle. Accordingly, this study aimed to identify other zinc-activating pathways in skeletal muscle cells to further delineate the role of this metal ion in cellular processes. Mouse C2C12 skeletal muscle cells were treated with insulin (10 nM), zinc (20 µM), and the zinc chelator TPEN (various concentrations) over 60 min. Western blots were performed for the zinc-activation of pAkt, pErk, and pCreb. A Cignal 45-Reporter Array that targets 45 signalling pathways was utilised to test the ability of zinc to activate pathways that have not yet been described. Zinc and insulin activated pAkt over 60 min as expected. Moreover, the treatment of C2C12 skeletal muscle cells with TPEN reduced the ability of zinc to activate pAkt and pErk. Zinc also activated several associated novel transcription factor pathways including Nrf1/Nrf2, ATF6, CREB, EGR1, STAT1, AP-1, PPAR, and TCF/LEF, and pCREB protein over 120 min of zinc treatment. These studies have shown that zinc's activity extends beyond that of insulin signalling and plays a role in modulating novel transcription factor activated pathways. Further studies to determine the exact role of zinc in the activation of transcription factor pathways will provide novel insights into this metal ion actions.
锌是一种参与许多生物过程的必需金属离子。研究表明，锌可以激活胰岛素信号通路中的几种分子，同时促进骨骼肌细胞对葡萄糖的摄取。然而，关于锌可以在骨骼肌中激活的其他潜在途径的信息有限。因此，本研究旨在鉴定锌在骨骼肌细胞中激活的其他途径，以进一步阐明该金属离子在细胞过程中的作用。用胰岛素（10 nM）、锌（20 µM）和锌螯合剂 TPEN（不同浓度）处理 C2C12 骨骼肌细胞 60 分钟。进行 Western blot 以检测锌对 pAkt、pErk 和 pCreb 的激活。利用靶向 45 种信号通路的 Cignal 45-Reporter Array 测试锌激活尚未描述的通路的能力。如预期的那样，锌和胰岛素在 60 分钟内激活了 pAkt。此外，用 TPEN 处理 C2C12 骨骼肌细胞会降低锌激活 pAkt 和 pErk 的能力。锌还激活了几种相关的新型转录因子途径，包括 Nrf1/Nrf2、ATF6、CREB、EGR1、STAT1、AP-1、PPAR 和 TCF/LEF，以及锌处理 120 分钟后的 pCREB 蛋白。这些研究表明，锌的活性超出了胰岛素信号通路的范围，在调节新型转录因子激活途径中发挥作用。进一步研究确定锌在转录因子途径激活中的确切作用将为该金属离子的作用提供新的见解。
