Stimulation of mechano-growth factor expression by second messengers.

The effect of second messengers on the expression of mechano-growth factor (MGF) synthesis by myoblasts and differentiated myotubes in culture was investigated. cAMP stimulates MGF expression both in murine and human cells. CNG- and HCN-channel blockers slightly activated MGF synthesis, while an activator of Epac protein had no effect. It is assumed that cAMP activates MGF synthesis via protein kinase A. Phorbol ester (PMA) activates MGF synthesis in human myoblasts and myotubes only. The expression of another splice form of IGF-1 gene, IGF-1Ea, was also stimulated in human cells by db-cAMP and PMA and in murine cells by db-cAMP only. Stimulation of MGF expression in human cells by db-cAMP and PMA demonstrated different time dependences but showed additivity when the compounds were applied in a combination. Inhibitors specific to protein kinase A did not affect PMA-mediated activation, while inhibitors specific to protein kinase C did not affect db-cAMP-mediated process. Ca²+ ionophore and ROS inductor strongly inhibited synthesis of the growth factor. PGE2 known as physiological stimulator of cAMP synthesis was shown to stimulate MGF expression both in murine and human cells. Implication of protein kinase A and protein kinase C in MGF synthesis stimulation and a cross-talk between two signaling systems is discussed.