title: Proto-oncogene expression in the isolated working rat heart: combination of pressure and volume overload with norepinephrine.
abstract: We have studied the effects of pressure and volume overload as well as of norepinephrine (NE) alone and in combination on the expression of the proto-oncogenes c-fos and c-myc in isolated perfused working rat hearts. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by Northern blots and quantified with densitometry. Total RNA was isolated from hearts after stimulation with NE (3 x 10(-8) M), after increasing left atrial filling pressure (preload) from 8 to 16 cmH2O, and after elevation of afterload from 80 to 100 cmH2O for 15, 30, 60, 90, and 120 min. NE increased the expression of c-fos and c-myc after 30 and 60 min, respectively. This enhancement occurred at about the same time as that induced by elevation of pre- and afterload, but was more pronounced. Combination of NE with pre- and afterload elevation induced the c-fos mRNA signal to appear earlier and to persist for a longer period of time. Similar results were obtained in regard to the c-myc mRNA, however, the signal was more pronounced in intensity. Simultaneous pre- and afterload increase also led to an earlier expression of the proto-oncogenes and to a longer duration of the signals. These results indicate that the combination of two hypertrophy-inducing stimuli, which may cause a higher degree of cardiac hypertrophy in vivo, induce an earlier, more pronounced and longer-lasting expression of the protooncogenes c-fos and c-myc.
authors.affiliation: Department of Physiology, University of Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kolbeck-Rühmkorff
authors.forename: H G
authors.initials: HG
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D016259:Genes, myc; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D009638:Norepinephrine