Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells
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 z...
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MDPI AG
2020-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/21/5098 |
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| author | Parisa Vahidi Ferdowsi Rachel Ng John Adulcikas Sukhwinder Singh Sohal Stephen Myers |
| author_facet | Parisa Vahidi Ferdowsi Rachel Ng John Adulcikas Sukhwinder Singh Sohal Stephen Myers |
| author_sort | Parisa Vahidi Ferdowsi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T15:08:10Z |
| format | Article |
| id | doaj.art-89228ea417554bae987e33df091f8778 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:08:10Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-89228ea417554bae987e33df091f87782023-11-20T19:36:44ZengMDPI AGMolecules1420-30492020-11-012521509810.3390/molecules25215098Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle CellsParisa Vahidi Ferdowsi0Rachel Ng1John Adulcikas2Sukhwinder Singh Sohal3Stephen Myers4College of Health and Medicine, School of Health Sciences, University of Tasmania, Newnham Campus, Launceston 7250, AustraliaCollege of Health and Medicine, School of Health Sciences, University of Tasmania, Newnham Campus, Launceston 7250, AustraliaCollege of Health and Medicine, School of Health Sciences, University of Tasmania, Newnham Campus, Launceston 7250, AustraliaCollege of Health and Medicine, School of Health Sciences, University of Tasmania, Newnham Campus, Launceston 7250, AustraliaCollege of Health and Medicine, School of Health Sciences, University of Tasmania, Newnham Campus, Launceston 7250, AustraliaZinc 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.https://www.mdpi.com/1420-3049/25/21/5098zincskeletal muscletranscription factorscell signallinginsulin |
| spellingShingle | Parisa Vahidi Ferdowsi Rachel Ng John Adulcikas Sukhwinder Singh Sohal Stephen Myers Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells Molecules zinc skeletal muscle transcription factors cell signalling insulin |
| title | Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells |
| title_full | Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells |
| title_fullStr | Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells |
| title_full_unstemmed | Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells |
| title_short | Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells |
| title_sort | zinc modulates several transcription factor regulated pathways in mouse skeletal muscle cells |
| topic | zinc skeletal muscle transcription factors cell signalling insulin |
| url | https://www.mdpi.com/1420-3049/25/21/5098 |
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