LONG-LASTING VITAMIN-C DERIVATIVE, ASCORBIC-ACID 2-PHOSPHATE, INCREASES MYOGENIN GENE-EXPRESSION AND PROMOTES DIFFERENTIATION IN L6 MUSCLE-CELLS

Hormones and growth factors are important regulators of myogenic cell differentiation, but little is known about the effect of vitamins on muscle differentiation and development. We recently showed that L-ascorbic acid 2-phosphate, a stable form of vitamin C, increased the expression of muscle-specific glucose and ion transporters. We now show the effect of L-ascorbic acid 2-phosphate on the kinetics of myogenin expression at both the mRNA and protein levels during differentiation of L6 muscle cells. At the fully differentiated stage, control and L-ascorbic acid 2-phosphate treated cultures showed the same degree of cell fusion, but L-ascorbic acid 2-phophate treated myotubes had a larger diameter than control myotubes. During L6 cell differentiation, the amount of both myogenin mRNA and protein reached a maximal level on day 4 before full myotube formation and then declined. L-ascorbic acid 2-phosphate treated cells expressed a higher amount of myogenin at both the mRNA and protein levels on day 4 compared to untreated cultures. Ethyl-3,4-dihydroxybenzoate, an inhibitor of collagen synthesis, prevented expression of myogenin mRNA and protein in both the control and L-ascorbic acid 2-phosphate treated cells. These results demonstrate that vitamin C can promote muscle differentiation likely through the increase of myogenin expression in myogenic cells, which may in turn regulate muscle differentiation in vivo. (C) 1994 Academic Press, Inc.