Localization of c-myc protooncogene expression in the rat heart in vivo and in the isolated, perfused heart following treatment with norepinephrine

We have investigated the expression of the protooncogene c-myc in rat hearts following exposure to norepinephrine, both in vivo and in isolated perfused preparations. Both chronic and acute norepinephrine treatment produced a rapid, transient elevation of c-myc mRNA in adult rat hearts, but chronic infusion produced a second, larger increase. This expression profile was characteristic for c-myc since it was not found for four other protooncogenes. In the isolated, perfused heart, addition of norepinephrine to the perfusion buffer and elevation of perfusion pressure separately increase c-myc mRNA suggesting both direct hormonal and hemodynamic factors might be important in vivo. Immunocytochemistry showed that Myc protein accumulated predominately in the nuclei of non-myocyte cells following norepinephrine treatment indicating that expression at the mRNA level culminated in protein synthesis. These findings suggest that the c-myc expression observed in the hypertrophying adult heart following exposure to norepinephrine may be associated with proliferating cells like fibroblasts rather than cardiomyocytes.