Alpha- and beta-adrenergic stimulation induces distinct patterns of immediate early gene expression in neonatal rat myocardial cells. fos/jun expression is associated with sarcomere assembly; Egr-1 induction is primarily an alpha 1-mediated response.
The present study was designed to determine if alpha- and beta-adrenergic stimulation of neonatal rat myocardial cells might induce common and/or distinct members of the immediate early gene program and to assess whether their induction might correlate with the differential effects of these adrenergic agonists on cardiac gene expression, sarcomere assembly, and several features of myocardial cell hypertrophy. Alpha- and beta-adrenergic stimulation of neonatal rat myocardial cells both produce an increase in the assembly of an individual contractile protein (myosin light chain-2) into organized sarcomeric units and also rapidly induce mRNAs for the immediate early genes c-fos and c-jun, thereby suggesting a potential role for these protooncogenes in sarcomerogenesis. alpha-Adrenergic stimulation results in the co-induction of mRNAs encoding a zinc finger protein gene (Egr-1). However, beta-adrenergic stimulation does not produce a significant increase in the levels of Egr-1 mRNA, providing the first evidence in any cell system that c-fos and Egr-1 expression can regulated separately. Studies with norepinephrine in combination with various adrenergic receptor antagonists revealed that the induction of Egr-1 is primarily an alpha 1-mediated, pertussis toxin-insensitive response. These studies provide the first evidence for the induction of immediate early genes following adrenergic stimulation of myocardial cells and demonstrate alpha- and beta-adrenergic stimulation can rapidly activate the expression of common and distinct subsets of these transcriptional regulators. Since alpha- and beta-adrenergic agonists have differential effects on cardiac gene expression and on the acquisition of several features of myocardial cell hypertrophy, the induction of Egr-1 provides a potential mechanism for the induction of genes that are exclusively induced during alpha-adrenergic-mediated myocardial cell hypertrophy.
Department of Medicine, University of California, La Jolla 92093.
K
K
Iwaki
V P
VP
Sukhatme
H E
HE
Shubeita
K R
KR
Chien
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects*; D005822:Genetic Vectors; D006321:Heart / Q000187:drug effects*; D017874:Immediate-Early Proteins; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes / Q000187:drug effects*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015183:Restriction Mapping; D012518:Sarcomeres / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; D012313:RNA; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D009638:Norepinephrine