Manganese influx and expression of ZIP8 is essential in primary myoblasts and contributes to activation of SOD2
| Autor: | Katherine E. Vest, Daniel E. Fenker, Shellaina J. V. Gordon, Teresita Padilla-Benavides |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death SOD2 Biophysics Gene Expression Biochemistry Article Muscle hypertrophy Myoblasts Biomaterials 03 medical and health sciences Enzyme activator medicine Animals Myocyte Cation Transport Proteins Cells Cultured Manganese Gene knockdown 030102 biochemistry & molecular biology Superoxide Dismutase Myogenesis Chemistry Metals and Alloys Skeletal muscle Transporter Cell biology Enzyme Activation Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Chemistry (miscellaneous) Gene Knockdown Techniques Second messenger system |
| Zdroj: | Metallomics |
| ISSN: | 1756-591X 1756-5901 |
| Popis: | Trace elements such as copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn) function as 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 metal transporters during differentiation of skeletal muscle cells. Here, we demonstrate that during differentiation of skeletal myoblasts an increase of Mn, Fe and Zn also 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 only by Mn supplementation to the medium, suggesting additional functions for ZIP8 in the skeletal muscle lineage. Restoring wild type Zip8 into the knockdown cells rescued the proliferation and differentiation phenotypes. On the other hand, knockdown of Zip14, had only a mild effect on myotube size, consistent with a role for ZIP14 in muscle hypertrophy. Simultaneous knockdown of both Zip8 and Zip14 further impaired differentiation and led cell death. 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 important modulators of mammalian tissue development. |
| Databáze: | OpenAIRE |
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