Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during α-adrenergic stimulation of neonatal rat ventricular cells: Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression

K. U. Knowlton, E. Baracchini, R. S. Ross, A. N. Harris, S. A. Henderson, S. M. Evans, C. C. Glembotski, K. R. Chien

Research output: Contribution to journalArticlepeer-review

217 Scopus citations

Abstract

To study the mechanisms which mediate the transcriptional activation of cardiac genes during α adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. α1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with α-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that α-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate α-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during α-adrenergic stimulation of neonatal rat ventricular cells.

Original languageEnglish (US)
Pages (from-to)7759-7768
Number of pages10
JournalJournal of Biological Chemistry
Volume266
Issue number12
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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