scholarly journals Hypoxic activation of the atrial natriuretic peptide gene promoter through direct and indirect actions of hypoxia-inducible factor-1

2003 ◽  
Vol 370 (1) ◽  
pp. 149-157 ◽  
Author(s):  
Yang-Sook CHUN ◽  
Ju-Yeon HYUN ◽  
Yong-Geun KWAK ◽  
In-San KIM ◽  
Chan-Hyung KIM ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Promoter Activity ◽  
Hypoxia Inducible Factor ◽  
Gene Promoter ◽  
Ventricular Myocardium ◽  
Dominant Negative ◽  
Hypoxia Inducible Factor 1 ◽  
Binding Sequence ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) is a cardiac peptide, the transcription of which is up-regulated in the ischaemic ventricle. However, the molecular mechanism of ANP induction is unclear. This study demonstrated that ANP mRNA expression in rat ventricular myocardium is induced in an early phase of ischaemia, preceded by hypoxia-inducible factor-1 (HIF-1) α expression. The ANP gene was also induced by hypoxia or HIF-1 inducers such as CoCl2 and desferrioxamine in H9c2 and neonatal cardiomyocytes. The 2307bp 5′-flanking region of the rat ANP gene was cloned and fused to the luciferase gene. Evidence of the promoter activity was only apparent in the myocytes and was induced by hypoxia and HIF-1 inducers. The overexpression of HIF-1α markedly enhanced ANP promoter activity, and a dominant-negative isoform completely suppressed it. We demonstrated that the promoter regions are essential for hypoxic ANP induction. One promoter region, containing the HIF-1-binding sequence, is regulated directly by HIF-1. The other region is also activated by HIF-1 despite having no HIF-1-binding sequence. These results suggest that HIF-1 enhances the transactivation of the ANP gene in hypoxic myocytes, implying that stimulation of the ANP promoter by HIF-1 may in fact be responsible for the induction of the ANP gene in ischaemic ventricular myocardium.

scholarly journals Vitamin D-dependent Suppression of Human Atrial Natriuretic Peptide Gene Promoter Activity Requires Heterodimer Assembly

1999 ◽  
Vol 274 (16) ◽  
pp. 11260-11266 ◽  
Author(s):  
Songcang Chen ◽  
Claudia H. R. M. Costa ◽  
Karl Nakamura ◽  
Ralff C. J. Ribeiro ◽  
David G. Gardner
Keyword(s):  
Vitamin D ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Promoter Activity ◽  
Gene Promoter ◽  
Human Atrial Natriuretic Peptide ◽  
Peptide Gene ◽  
Atrial Natriuretic

Ischemia stimulates the release of atrial natriuretic peptide from rat cardiac ventricular myocardium in vitro

Life Sciences ◽  
1992 ◽  
Vol 50 (5) ◽  
pp. 365-373 ◽  
Author(s):  
Paavo A. Uusimaa ◽  
Keijo J. Peuhkurinen ◽  
Ilmo E. Hassinen ◽  
Olli Vuolteenaho ◽  
Heikki Ruskoaho
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Ventricular Myocardium ◽  
Atrial Natriuretic

Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis

2015 ◽  
Vol 308 (7) ◽  
pp. C557-C569 ◽  
Author(s):  
Adam Hotchkiss ◽  
Tiam Feridooni ◽  
Mark Baguma-Nibasheka ◽  
Kathleen McNeil ◽  
Sarita Chinni ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Progenitor Cells ◽  
Natriuretic Peptide ◽  
Biological Effects ◽  
Active Form ◽  
Specific Inhibitor ◽  
Ventricular Myocardium ◽  
Biologically Active ◽  
Cardiac Progenitor Cells ◽  
Atrial Natriuretic

The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways.

scholarly journals The protein tyrosine kinase inhibitor genistein suppresses hypoxia-induced atrial natriuretic peptide secretion mediated by the PI3K/Akt-HIF-1α pathway in isolated beating rat atria

2021 ◽  
pp. 1-7
Author(s):  
Qiu-li Zhang ◽  
Ping Li ◽  
Lan Hong ◽  
Rui-zhuang Li ◽  
Jia-qi Wang ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Tyrosine Kinase ◽  
Natriuretic Peptide ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Acute Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Protein Tyrosine ◽  
Downstream Signaling ◽  
Atrial Natriuretic

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, has been shown to play pivotal roles in the signal transduction pathways of hypoxic disorders. In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced atrial natriuretic peptide (ANP) secretion. Radioimmunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor 1α (HIF-1α), and GATA4 in the atrial tissue. The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 μM). By Western blotting analysis, we found that hypoxia-induced increase in phosphorylation of Akt and transcriptional factors, including HIF-1α, were also reversed by genistein. The perfused HIF-1α inhibitors rotenone (0.5 μM) or CAY10585 (10 μM) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist insulin-like growth factor 1 (30 μM) also abolished ANP secretion induced by genistein and inhibited expression of HIF-1α. In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the phosphoinositide-3 kinase (PI3K)/HIF-1α dependent pathway.

scholarly journals Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos.

1992 ◽  
Vol 12 (1) ◽  
pp. 292-301 ◽  
Author(s):  
B Kovacic-Milivojević ◽  
D G Gardner
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Transcriptional Activation ◽  
Gene Promoter ◽  
Regulatory Elements ◽  
Neonatal Rat ◽  
Regulatory Sequence ◽  
Mobility Shift ◽  
Human Atrial Natriuretic Peptide ◽  
Atrial Natriuretic

Employing transient transfection analysis in neonatal rat cardiocytes, we have demonstrated that overexpression of c-jun results in a dose-dependent induction of the human atrial natriuretic peptide (hANP) gene promoter. Studies using a series of mutations in the hANP gene promoter identified a TRE-like, cis-acting regulatory sequence which conferred c-jun sensitivity. This same region was shown to interact with the c-jun/c-fos complex in an in vitro gel mobility shift assay. Selective mutation of this site suppressed basal activity of the hANP promoter and significantly reduced c-jun-dependent activation. Overexpression of c-fos had a biphasic effect on hANP gene promoter activity. At low levels, in concert with c-jun, it activated, while at higher levels it suppressed, transcription from the hANP gene promoter. This inhibition was both cell and promoter specific. hANP gene promoter sequences which mediate c-fos-dependent inhibition appear to be separable from those responsible for the induction. In addition, the protein domains on c-fos responsible for transcriptional activation and repression can be segregated topographically, with the inhibitory activity being localized to the carboxy-terminal domain. Thus, c-fos can activate or repress hANP gene expression through two separate functional domains that act on distinct regulatory elements in the hANP gene promoter. These data imply that the ANP gene may be a physiological target for c-fos- and c-jun-dependent activity in the heart and suggest a potential mechanism linking environmental stimuli to its expression.

scholarly journals Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1αas Adaptive Response to a High Salt Diet

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Silvana Lorena Della Penna ◽  
Gabriel Cao ◽  
Andrea Carranza ◽  
Elsa Zotta ◽  
Susana Gorzalczany ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Adaptive Response ◽  
Hypoxia Inducible Factor ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sodium Overload ◽  
Atrial Natriuretic

In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1αis involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP andUVNalevels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1αcompared to their control. These findings suggest that HIF-1αand ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis.Erratum to “Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet”

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