Determinants of inducible brain natriuretic peptide promoter activity

Atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are polypeptide hormones belonging to the cardiac-derived mammalian natriuretic peptide system. These hormones share the same biological properties and receptors and both play important roles in the maintenance of fluid and electrolyte balance and in cardiovascular growth. Most hemodynamic and neurohumoral stimuli can coordinately increase ANF and BNP gene expression. However, instances of discoordinated ANF and BNP gene expression have been described, providing an opportunity for investigating the mechanisms that differentially regulate the expression of the natriuretic peptide genes. For example, exposure of cardiocytes in culture to certain pro-inflammatory cytokines and conditioned medium from mixed lymphocyte cultures upregulate BNP but not ANF gene expression. BNP promoter activity is also upregulated under these conditions but the cis-acting elements involved in this phenomenon are not known. In comparison to the ANF gene, less is known about BNP promoter consensus elements that regulate gene expression by mechanical or neurohumoral agonists. A number of cis-acting elements for GATA, Nkx2.5, NF-kappaB and TEF transcription factors have recently been identified within the BNP promoter that regulate BNP expression in response to specific agonists. This review focuses on the information available regarding cis-acting determinants responsible for inducible BNP transcription.