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Zinc modulates several transcription-factor regulated pathways in mouse skeletal muscle cells

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Vahidi Ferdowsi, P, Ng, R, Adulcikas, J ORCID: 0000-0001-9193-6709, Sohal, SS ORCID: 0000-0001-9627-6498 and Myers, S ORCID: 0000-0003-4793-3820 2020 , 'Zinc modulates several transcription-factor regulated pathways in mouse skeletal muscle cells' , Molecules, vol. 25, no. 21 , pp. 1-15 , doi: 10.3390/molecules25215098.

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Abstract

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.

Item Type: Article
Authors/Creators:Vahidi Ferdowsi, P and Ng, R and Adulcikas, J and Sohal, SS and Myers, S
Keywords: zinc, skeletal muscle, transcription factors, cell signalling, insulin
Journal or Publication Title: Molecules
Publisher: Molecular Diversity Preservation International
ISSN: 1420-3049
DOI / ID Number: 10.3390/molecules25215098
Copyright Information:

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license http://creativecommons.org/licenses/by/4.0/.

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