Zinc and the initiation of myoblast differentiation

Abstract

Previous studies have indicated that a lack of available zinc inhibited myoblast differentiation as shown by a failure of the cells to fuse and low expression of creatine kinase mRNA and activity. However, the nature of the requirement for zinc and its relationship to the events leading to differentiation have been unclear. The current studies with C 2C 12 cells indicated that the muscle-specific enhancer present in the 5′-flanking region of the creatine kinase gene contributed to the zinc sensitivity of this enzyme. Because this enhancer can be activated by expression of the myogenic factors MyoD and myogenin, their sensitivity to zinc was investigated. The concentrations of both MyoD and, particularly, myogenin mRNA, were decreased by zinc deficiency. In vitro translation experiments suggested that these changes closely corresponded with alterations in their rates of synthesis. Further experiments failed to indicate a major effect of zinc on the stabilities of these mRNAs. Because an induction of myogenin mRNA is one of the earliest known events in myoblast differentiation, its particular sensitivity to lack of zinc suggests that zinc may be required before or during the initiation of myoblast differentiation.