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 isola ted perfused preparations. Both chronic and acute norepinephrine treat ment 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, addit ion of norepinephrine to the perfusion buffer and elevation of perfusi on pressure separately increase c-myc mRNA suggesting both direct horm onal and hemodynamic factors might be important in vivo. Immunocytoche mistry showed that Myc protein accumulated predominately in the nuclei of non-myocyte cells following norepinephrine treatment indicating th at expression at the mRNA level culminated in protein synthesis. These findings suggest that the c-myc expression observed in the hypertroph ying adult heart following exposure to norepinephrine may be associate d with proliferating cells like fibroblasts rather than cardiomyocytes .