Dataset Information

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development.

ABSTRACT: Organ development is a highly regulated process involving the coordinated proliferation and differentiation of diverse cellular populations. The pathways regulating cell proliferation and their effects on organ growth are complex and for many organs incompletely understood. In all vertebrate species, the cardiac natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the developing heart. However, their role during cardiogenesis is not defined. Using the embryonic zebrafish and neonatal mammalian cardiomyocytes we explored the natriuretic peptide signaling network during myocardial development. We observed that the cardiac natriuretic peptides ANP and BNP and the guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2 are functionally redundant during early cardiovascular development. In addition, we demonstrate that low levels of the natriuretic peptides preferentially activate Npr3, a receptor with Gi activator sequences, and increase cardiomyocyte proliferation through inhibition of adenylate cyclase. Conversely, high concentrations of natriuretic peptides reduce cardiomyocyte proliferation through activation of the particulate guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2, and activation of protein kinase G. These data link the cardiac natriuretic peptides in a complex hierarchy modulating cardiomyocyte numbers during development through opposing effects on cardiomyocyte proliferation mediated through distinct cyclic nucleotide signaling pathways.

SUBMITTER: Becker JR

PROVIDER: S-EPMC3879815 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development.

Becker Jason R JR Chatterjee Sneha S Robinson Tamara Y TY Bennett Jeffrey S JS Panáková Daniela D Galindo Cristi L CL Zhong Lin L Shin Jordan T JT Coy Shannon M SM Kelly Amy E AE Roden Dan M DM Lim Chee Chew CC MacRae Calum A CA

Development (Cambridge, England) 20131218 2

Organ development is a highly regulated process involving the coordinated proliferation and differentiation of diverse cellular populations. The pathways regulating cell proliferation and their effects on organ growth are complex and for many organs incompletely understood. In all vertebrate species, the cardiac natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the developing heart. However, their role during cardiogenesis is not defined. Using the embryonic zebrafish and neon ...[more]

PMID: 24353062

Similar Datasets

Project description:Atrionatriuretic peptide (ANP) lowers intraocular pressure in the eyes of humans and rabbits. We examined the effects of natriuretic peptides on cGMP formation and 125I-labelled-ANP binding to cultured cells derived from ciliary body epithelium, the site of aqueous humour formation in the eye. ANP, brain natriuretic peptide (BNP) and C-natriuretic peptide (CNP) at 1 microM stimulated cGMP formation 8.2(+/-1.2)-fold, 4.8(+/-0.6)-fold and 87.3(+/-12.1)-fold respectively. 125I-ANP bound to intact cells at a single site, with a dissociation constant KD=0.30+/-0.01 nM. BNP was as effective as ANP in displacing 125I-ANP, whereas CNP displaced label with a slightly higher IC50. 125I-ANP binding was displaced >95% by c-ANP, a specific ligand for natriuretic peptide C receptors (NPR-C). Cross-linking of 125I-ANP to cells labelled predominantly a protein of Mr 62000. These data suggest that 125I-ANP binding was primarily to NPR-C, whereas cGMP stimulation occurred primarily via natriuretic peptide B receptors (NPR-B). Vasopressin and histamine, both activators of the inositol phosphate/diacylglycerol phosphate pathway in non-pigmented ciliary epithelial cells, inhibited CNP stimulation of guanylate cyclase (NPR-B) and 125I-ANP binding (NPR-C) by 30-38%. Inhibition was mimicked by PMA, dioctanoylglycerol and phorbol didecanoate, whereas 4alpha phorbol didecanoate had no effect. Staurosporine and bisindolylmaleimide both blocked inhibition of 125I-ANP binding and cGMP formation by PMA. These results suggest that protein kinase C (PKC) down-regulates both NPR-B and NPR-C. PKC down-regulation of NPR-B varied inversely with CNP concentration. Inhibition by 1 microM PMA was 30.6(+/-4.0)% with 500 nM CNP, but 83.4(+/-8.8)% with 10 nM CNP, indicating that increasing CNP could partially overcome inhibition by PMA. Since extracellular CNP levels were not affected by PKC activation, the effect of PKC on NPR-B is best explained as a reduction in NPR-B affinity for CNP. NPR-C measured as 125I-ANP binding was likewise reduced 36.4(+/-5.1)% by exposure to PMA. In contrast with NPR-B inhibition, however, inhibition of NPR-C was due largely to a reduction in the number of receptor binding sites per cell rather than a reduction in receptor affinity for ligand. The data therefore suggest that both NPR-B and NPR-C are down-regulated by PKC, but that the mechanisms of down-regulation of the two receptors are different.

Project description:Purpose:Natriuretic peptides (NPs) negatively feedback on the renin-angiotensin-aldosterone system (RAAS) and play a critical role in preserving cardiac structure and maintaining metabolic homeostasis. Well-treated HIV-infected individuals are at risk for fat redistribution and demonstrate evidence of RAAS dysregulation, which relates to metabolic dysfunction. We investigated circulating NPs in relation to RAAS physiology and metrics of body composition in HIV. Methods:We assessed atrial natriuretic peptide, brain natriuretic peptide (BNP), and amino terminal pro B-type natriuretic peptide (NT-proBNP) during acute activation of the RAAS using a low-sodium controlled diet among 20 HIV-infected and 10 non-HIV-infected individuals well phenotyped for body composition. Results:BNP was significantly lower [median, 60 (interquartile range, 44, 152) pg/mL vs 196 (91, 251) pg/mL, respectively; P = 0.04], and serum aldosterone was higher, among HIV-infected than among non-HIV-infected individuals. BNP was significantly and inversely associated with body composition [waist circumference: r = -0.46 (P = 0.04); BMI: r = -0.55 (P = 0.01); body adiposity index: r = -0.49 (P = 0.03)], metabolic indices [total cholesterol: r = -0.44 (P = 0.05), insulin resistance calculated by using homeostatic model assessment: r = -0.44 (P = 0.05); mean arterial pressure: r = -0.44 (P = 0.05)], and serum aldosterone (r = -0.49; P = 0.03) among the HIV-infected group. These relationships were not demonstrated in the non-HIV-infected group. In a four-group comparison stratifying by HIV serostatus and above or below a body mass index (BMI) of 25 kg/m2, BNP decreased significantly across groups; it was highest in non-HIV-infected patients with a BMI <25 kg/m2 and lowest in HIV-infected patients with a BMI ?25 kg/m2 (overall P = 0.01). Conclusion:Relatively reduced NP, particularly BNP, among HIV-infected individuals with excess adiposity may contribute to reduced suppression of aldosterone and potentially drive aldosterone-mediated metabolic complications. Strategies that target RAAS blockade and/or augment NPs may be useful to reduce cardiometabolic disease among HIV-infected individuals in whom these systems are perturbed.

Dataset Information

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development.

Publications

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure