Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10836241 | Peptides | 2005 | 13 Pages |
Abstract
After brain natriuretic peptide (BNP) was isolated in 1988, rapid progress was made in cloning its cDNA and gene, facilitating studies of tissue-specific expression and molecular regulation of gene expression. This review focuses on the molecular determinants of regulation of the rat and human BNP genes, including signaling pathways that impact on changes in gene expression and cis regulatory elements responsive to these signaling pathways. For both rat and human genes, elements in the proximal promoter (â124 to â80), including GATA, MCAT, and AP-1-like, have been shown to contribute to basal and inducible regulation. More distal elements in the human BNP gene respond to calcium signals (an NF-AT site at â927), thyroid hormone (a thyroid-responsive element at â1000), and mechanical stretch (shear stress-responsive elements at â652 and â162). Understanding how BNP is regulated by signaling molecules that are activated in the hypertrophied and ischemic heart should be useful in understanding the underlying pathology. This may lead to therapeutic strategies that prevent hypertrophy while allowing for the beneficial effects of BNP production.
Keywords
PI3KTEFcalcium/calmodulin kinase IIBNPNF-ATPKCSSRE1-Phosphatidylinositol 3-kinaseFriend of GATAAP-1NRSEpKaCaMKIImyocyte enhancer factorbrain or b-type natriuretic peptideATFMEFANPmCATCRE3′ untranslated region3′UTRMAPKendothelin 1ISOisoproterenolInterleukin-1βGene expressionTherapeutic5′ flanking sequenceNuclear Factor of Activated T Cellsneuron-restrictive silencer elementcAMP-responsive elementactivating transcription factorphenylephrineFogHypertrophyactivator protein-1protein kinase AProtein kinase Cmitogen-activated protein kinasePeptideatrial natriuretic peptide
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Authors
Margot C. LaPointe,