Roles of Zip8 and Zip14 Transporters in Myogenesis

Abstract

Transition metals like manganese (Mn) are necessary catalytic and structural cofactors in enzymes and as second messengers in cell signaling. Studies on the molecular mechanisms by which Mn contributes to development are focused on its role as co‐factor of the mitochondrial enzyme superoxide dismutase 2 (SOD2). However, Mn has been proposed to participate in protein glycosylation during bone and neural development. Our laboratory is investigating the biological relevance of Mn in the differentiation of skeletal muscle cells. During myogenesis, total mitochondrial content increases and cells increase expression of SOD2, which protects against oxidative stress. Our lab has shown that the gene and protein levels of ZIP8 and ZIP14, two membrane Zn/Mn transporters, increase during differentiation of the C2C12 immortalized mouse myoblasts. Preliminary data shows a significant increase in the cellular Mn quota during the differentiation of primary myoblasts derived from mouse satellite cells, which are the stem cell pool that sustains and regenerates myofibers in adult skeletal muscle. We hypothesized that ZIP8 and ZIP14 might be associated with the Mn influx during myogenesis. To determine the role of ZIP8, ZIP14, and Mn during myogenesis we used shRNA to delete Zip8 and Zip14 transporters in primary myoblasts derived from primary myoblasts. Partial deletion of these transporters resulted in changes in cellular Mn levels. Zip8 knockdown myoblasts are unable to differentiate compared to control and Zip14 knockdown myoblasts, as shown by the expression of muscle‐specific differentiation markers and alterations on the morphology of differentiating cells. Sod2 activity is reduced also in Zip8 knockdown myoblasts. This work will contribute considerably to the very limited literature related to Mn biology in myogenesis and would provide a foundation for future efforts to understand the contribution of Mn in other differentiation and disease models.Support or Funding InformationThis project was funded by the Faculty Diversity Scholars Award from the University of Massachusetts Medical School Awarded to TP‐B. S. Gordon is supported by the NIH Grant R25 HL092610‐11This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.