AFos dissociates cardiac myocyte hypertrophy and expression of the pathological gene program

被引:38
作者
Jeong, MY
Kinugawa, K
Vinson, C
Long, CS
机构
[1] Denver Hlth Med Ctr, Cardiol Sect, Denver, CO 80204 USA
[2] Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan
[3] Natl Canc Inst, Bethesda, MD USA
关键词
hypertrophy; signal transduction; myocytes; molecular biology;
D O I
10.1161/01.CIR.0000160367.99928.87
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. Methods and 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 (beta MHC), atrial/brain natriuretic peptides (ANP/BNP), and skeletal alpha-actin (sACT) was increased, whereas expression for alpha-myosin heavy chain (alpha MHC) 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 alpha MHC 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.
引用
收藏
页码:1645 / 1651
页数:7
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