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dc.contributor.authorGordon, Shellaina J. V.
dc.contributor.authorFenker, Daniel E.
dc.contributor.authorVest, Katherine E.
dc.contributor.authorPadilla-Benavides, Teresita
dc.date2022-08-11T08:08:23.000
dc.date.accessioned2022-08-23T15:53:34Z
dc.date.available2022-08-23T15:53:34Z
dc.date.issued2018-12-12
dc.date.submitted2018-12-26
dc.identifier.citation<p>bioRxiv 494542; doi: https://doi.org/10.1101/49454. <a href="https://doi.org/10.1101/494542" target="_blank">Link to preprint on bioRxiv service.</a></p>
dc.identifier.doi10.1101/494542
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29380
dc.description.abstractTrace elements such as copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn) are enzyme cofactors and second messengers in cell signaling. Trace elements are emerging as key regulators of differentiation and development of mammalian tissues including blood, brain, and skeletal muscle. We previously reported an influx of Cu and dynamic expression of various metal transporters during differentiation of skeletal muscle cells. Here, we demonstrate that during differentiation of skeletal myoblasts an increase of additional trace elements such as Mn, Fe and Zn occurs. Interestingly the Mn increase is concomitant with increased Mn-dependent SOD2 levels. To better understand the Mn import pathway in skeletal muscle cells, we probed the functional relevance of the closely related proteins ZIP8 and ZIP14, which are implicated in Zn, Mn, and Fe transport. Partial depletion of ZIP8 severely impaired growth of myoblasts and led to cell death under differentiation conditions, indicating that ZIP8-mediated metal transport is essential in skeletal muscle cells. Moreover, knockdown of Zip8 impaired activity of the Mn-dependent SOD2. Growth defects were partially rescued by Mn supplementation to the medium, suggesting additional functions for ZIP8 in the skeletal muscle lineage. Knockdown of Zip14, on the other hand, had only a mild effect on myotube size, consistent with a role for ZIP14 in muscle hypertrophy. This is the first report on the functional relevance of two members of the ZIP family of metal transporters in the skeletal muscle lineage, and further supports the paradigm that trace metal transporters are critical modulators of mammalian tissue development.
dc.language.isoen_US
dc.relationNow published in Metallomics doi: 10.1039/C8MT00348C
dc.rightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectmyogenesis
dc.subjectmanganese
dc.subjectZIP8
dc.subjectZIP14
dc.subjectSuperoxide dismutase 2 (SOD2)
dc.subjectcell biology
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectEnzymes and Coenzymes
dc.subjectInorganic Chemicals
dc.titleManganese influx and expression of ZIP8 is essential in primary myoblasts and contributes to activation of SOD2 [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2619&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1609
dc.identifier.contextkey13535655
refterms.dateFOA2022-08-23T15:53:34Z
html.description.abstract<p>Trace elements such as copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn) are enzyme cofactors and second messengers in cell signaling. Trace elements are emerging as key regulators of differentiation and development of mammalian tissues including blood, brain, and skeletal muscle. We previously reported an influx of Cu and dynamic expression of various metal transporters during differentiation of skeletal muscle cells. Here, we demonstrate that during differentiation of skeletal myoblasts an increase of additional trace elements such as Mn, Fe and Zn occurs. Interestingly the Mn increase is concomitant with increased Mn-dependent SOD2 levels. To better understand the Mn import pathway in skeletal muscle cells, we probed the functional relevance of the closely related proteins ZIP8 and ZIP14, which are implicated in Zn, Mn, and Fe transport. Partial depletion of ZIP8 severely impaired growth of myoblasts and led to cell death under differentiation conditions, indicating that ZIP8-mediated metal transport is essential in skeletal muscle cells. Moreover, knockdown of Zip8 impaired activity of the Mn-dependent SOD2. Growth defects were partially rescued by Mn supplementation to the medium, suggesting additional functions for ZIP8 in the skeletal muscle lineage. Knockdown of Zip14, on the other hand, had only a mild effect on myotube size, consistent with a role for ZIP14 in muscle hypertrophy. This is the first report on the functional relevance of two members of the ZIP family of metal transporters in the skeletal muscle lineage, and further supports the paradigm that trace metal transporters are critical modulators of mammalian tissue development.</p>
dc.identifier.submissionpathfaculty_pubs/1609
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology


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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.