AFos dissociates cardiac myocyte hypertrophy and expression of the pathological gene program.
BACKGROUND
Although induction of activator protein-1 (AP-1) transcription factor activity has been observed in cardiac hypertrophy, a direct role for AP-1 in myocardial growth and gene expression remains obscure.


RESULTS
Hypertrophy was induced in cultured neonatal rat cardiomyocytes with phenylephrine or overexpression of a constitutively active MAP3K, MKK6. In both treatment groups, induction of the pathological gene profile was observed, ie, expression of beta-myosin heavy chain (betaMHC), atrial/brain natriuretic peptides (ANP/BNP), and skeletal alpha-actin (sACT) was increased, whereas expression for alpha-myosin heavy chain (alphaMHC) and the sarcoplasmic reticulum Ca2+-ATPase (SERCA) genes was repressed. The role of AP-1 in the hypertrophic phenotype was evaluated with the use of an adenoviral construct expressing a dominant negative mutant of the c-Fos proto-oncogene (AdAFos). Although AFos did not change the myocyte growth response, it abrogated the gene profile to both agonists, including the upregulation of both alphaMHC and SERCA expression.


CONCLUSIONS
Although c-Fos/AP-1 is necessary for induction of the pathological/fetal gene program, it does not appear to be critical for cardiomyocyte hypertrophy.
Jeong
Mark Y
MY
Cardiology Section, Denver Health Medical Center, Denver, Colo 80204, USA.
Kinugawa
Koichiro
K
Vinson
Charles
C
Long
Carlin S
CS
D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics / Q000502:physiology*; D006984:Hypertrophy / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014161:Transduction, Genetic
D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1