The skeletal α-actin gene is expressed in fetal rat heart and is induced during norepinephrine (NE)-stimulated hypertrophy in cultures of neonatal rat cardiac myocytes. Here we report that NE positively regulates the human skeletal α-actin gene promoter in transiently transfected neonatal rat cardiac myocytes. NE increased expression from the full-length promoter by 2.4-fold. A DNA region required for NE responsiveness but not for tissue-specific expression was located between base pair -2000 and base pair -1300. Distinct regions required for cardiac myocyte expression were located between -1300 to -710 and -153 to -87. None of these elements separately conferred tissue specificity or adrenergic responsiveness on a heterologous promoter, although the intact promoter from -2000 to -36 conferred both when cloned in its correct position and orientation. Additional elements in the basal promoter (-87 to +187) were required for maximal NE responsiveness. The NE induction was mediated by the β-adrenergic receptor in high-density cultures (3-4 × 106 cells per 60-mm dish), as was induction of hypertrophy, contractility, and endogenous skeletal α-actin gene expression. The β-adrenergic agonist isoproterenol was as potent as NE in inducing expression. Furthermore, β-adrenergic antagonists inhibited the effects on skeletal α-actin gene expression but α1-adrenergic antagonists did not. The α1-adrenergic system was intact in these high-density cultures, since the effects of NE on the expression of another contractile protein gene, α-myosin heavy chain, were blocked by α1 but not by β-adrenergic antagonists. In these high-density cultures, cell contact and intermyocardiocyte bridging were prevalent. When cardiac myocytes were plated at a low density, minimizing cell contact, NE induction of skeletal α-actin gene expression and hypertrophy was mediated by the α1-adrenoceptor. Factors related to cell communication may influence the pathways mediating NE-regulated gene transcription during cardiac myocyte hypertrophy.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1991|
- Cell contact
- Myosin heavy chain
ASJC Scopus subject areas