Regulation of Gene Expression
The natriuretic peptides are expressed predominantly by cardiomyocytes of the mixed secretory-contractile phenotype in atrial and ventricular walls. The genes are located in a typical gene cluster consisting of three genes in mammals:
NPPA,
NPPB, and
NPPC (natriuretic peptide precursor A/B/C). All three genes are controlled by a wide variety of transcription regulatory elements that drive gene expression of each of these three genes individually or in common, with many biological scenarios leading to the simultaneous expression of ANP and BNP. Furthermore, mature natriuretic peptides are expressed as prepro-natriuretic peptides that require a series of maturation steps mediated by cleavage enzymes. In an initial step, signal peptidases remove the targeting signal necessary for correct processing through the endoplasmic reticulum and the Golgi apparatus, resulting in the pro-peptide. Corin or furin endopeptidase cleaves the pro-peptide into a hormonally inactive N-terminal peptide and the hormone natriuretic peptide. The N-terminal peptides of ANP, BNP, and CNP are most commonly termed mid-regional proANP (MR-proANP), N-terminal proBNP (NT-proBNP), and NT-proCNP, respectively. The functional hormones are all stabilized by a cysteine-anchored disulfite bond forming a 17-amino acid central ring in the peptide essential for their biological activity. Both N-terminal pro-peptide and mature natriuretic hormone are stored together in atrial (appendage) storage granules within cardiomyocytes and are secreted together in a 1:1 ratio.
Natriuretic peptides are secreted upon various stimuli and contribute to the physiological regulation of cardiovascular function and renal clearance. ANP and BNP are especially released upon cardiac stress and failure due to inflammation and stretch stimuli, and act on natriuretic peptide receptors (NPR) A, B, and C. NPRA and NPRB are guanylyl cyclase-linked receptors which convert GDP to cGMP, which in turn modulates various functions in the respective target cells. NRPC is mostly a clearance receptor that helps eliminate circulating natriuretic peptides.
NT-proBNP as a Marker of Cardiac Failure
The remarkable relation between N-terminal pro-peptides and effector peptide hormones is their co-secretion in a 1:1 ratio. As the N-terminal pro-peptides show remarkably longer half-lives than the respective effector hormone, they are ideal candidates as biomarkers for cardiac stress and failure. Given that under most common clinical scenarios ANP and BNP are secreted in approximately equal parts, especially NT-proBNP has proven to be a reliable diagnostic marker to aid clinicians in assessing cardiac status.
BNP Signalling at Enzo Life Sciences
Enzo Life Sciences offers a comprehensive product portfolio for
metabolic research and
hormonal regulation. Our
BNP Fragment ELISA kit provides a sensitive, quantitative determination of human NT-proBNP fragment in serum and plasma.
Do you have any questions regarding our products or their implementation into your research? Please contact our
Technical support team for more information. We will be happy to assist.
Fast Facts:
- Cardiomyocytes secrete natriuretic peptides in response to stress.
- Natriuretic peptides regulate cardiovascular function and renal clearance.
- NT-proBNP is a crucial diagnostic biomarker for the assessment of heart failure.
