The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Among these, ANP and BNP are secreted by the heart and act as cardiac hormones. Both ANP and BNP preferentially bind to natriuretic peptide receptor-A (NPR-A or guanylyl cyslase-A) and exert similar effects through increases in intracellular cyclic guanosine monophosphate (cGMP) within target tissues. Expression and secretion of ANP and BNP are stimulated by various factors and are regulated via multiple signaling pathways. Human ANP has three molecular forms, α-ANP, β-ANP, and proANP (or γ-ANP), with proANP predominating in healthy atrial tissue. During secretion proANP is proteolytically processed by corin, resulting in secretion of bioactive α-ANP into the peripheral circulation. ProANP and β-ANP are minor forms in the circulation but are increased in patients with heart failure. The human BNP precursor proBNP is proteolytically processed to BNP1-32 and N-terminal proBNP (NT-proBNP) within ventricular myocytes. Uncleaved proBNP as well as mature BNP1-32 and NT-proBNP is secreted from the heart, and its secretion is increased in patients with heart failure. Mature BNP, its metabolites including BNP3-32, BNP4-32, and BNP5-32, and proBNP are all detected as immunoreactive-BNP by the current BNP assay system. We recently developed an assay system that specifically detects human proBNP. Using this assay system, we observed that miR30-GALNTs-dependent O-glycosylation in the N-terminal region of proBNP contributes to regulation of the processing and secretion of proBNP from the heart.
Keywords: ANP; BNP; Natriuretic peptides; O-glycosylation.
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