Birgit Gaßner's research while affiliated with University of Wuerzburg and other places

Publications (65)

Article
Aims: Cardiac hypertrophy is a common and often lethal complication of arterial hypertension. Elevation of myocyte cyclic GMP levels by local actions of endogenous atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) or by pharmacological inhibition of phosphodiesterase-5 was shown to counter-regulate pathological hypertrophy. It w...
Article
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The cardiac hormone atrial natriuretic peptide (ANP) regulates systemic and pulmonary arterial blood pressure by activation of its cyclic GMP-producing guanylyl cyclase-A (GC-A) receptor. In the lung, these hypotensive effects were mainly attributed to smooth muscle-mediated vasodilatation. It is unknown whether pulmonary endothelial cells particip...
Article
Aims Cardiac atrial natriuretic peptide (ANP) participates in the maintenance of arterial blood pressure and intravascular volume homeostasis. The hypovolaemic effects of ANP result from coordinated actions in the kidney and systemic microcirculation. Hence, ANP, via its guanylyl cyclase-A (GC-A) receptor and intracellular cyclic GMP as second mess...
Article
Background: The endocrine balance between atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system is critical for the maintenance of arterial blood pressure and volume homeostasis. This study investigated whether a cardiac imbalance between ANP and aldosterone, toward increased mineralocorticoid receptor (MR) signaling, contr...
Article
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BackgroundC-type natriuretic peptide (CNP)/natriuretic peptide receptor 2 (NPR2) signalling is essential for long bone growth. Enhanced CNP production caused by chromosomal translocations results in tall stature, a Marfanoid phenotype and skeletal abnormalities. A similar phenotype was described in a family with an activating NPR2 mutation within t...
Article
Full-text available
Background. C-type natriuretic peptide (CNP)/natriuretic peptide receptor 2 (NPR2) signalling is essential for long bone growth. Enhanced CNP production caused by chromosomal translocations results in tall stature, a Marfanoid phenotype and skeletal abnormalities. A similar phenotype was described in a family with an activating NPR2 mutation within...
Article
Full-text available
Atrial natriuretic peptide (ANP), via its cGMP-forming guanylyl cyclase-A (GC-A) receptor, is critically involved in the regulation of arterial blood pressure and intravascular volume. To elucidate the role of the endothelial effects of ANP, we generated mice with conditional, endothelium (EC)-restricted ablation of the GC-A gene. Our observations...
Article
Full-text available
Background Atrial natriuretic peptide (ANP), via its guanylyl cyclase A (GC-A) receptor and cyclic GMP formation, exerts cardiac antihypertrophic and antifibrotic actions. Conversely, aldosterone promotes pathological cardiac remodeling via the mineralocorticoid receptor (MR). To investigate whether local cardiac ANP/GC-A signaling counteracts the...
Conference Paper
Full-text available
Pulmonary arterial hypertension (PAH) is a rare progressive, usually fatal lung disease of different ethiologies. Endothelial cell dysfunction contributes to the pathogenesis, although the specific mechanisms are not clear. Impaired vascular cGMP signaling seems to be involved in the development of pulmonary vascular remodeling and constriction, be...
Article
Histamine increases microvascular endothelial leakage by activation of complex calcium-dependent and -independent signaling pathways. Atrial natriuretic peptide (ANP) via its cGMP-forming guanylyl cyclase-A (GC-A) receptor counteracts this response. Here, we characterized the molecular mechanisms underlying this interaction, especially the role of...
Article
Calcium-sensitive potassium channels (K(Ca)3.1) are expressed in virtually all migrating cells. Their activity is required for optimal cell migration so that their blockade leads to slowing down. K(Ca)3.1 channels must be inserted into the plasma membrane in order to elicit their physiological function. However, the plasma membrane of migrating cel...
Article
Full-text available
Cardiac atrial natriuretic peptide (ANP) participates in the maintenance of arterial blood pressure and intravascular volume homeostasis. The hypovolaemic effects of ANP result from coordinated actions in the kidney and systemic microcirculation. Hence, ANP, via its guanylyl cyclase-A (GC-A) receptor and intracellular cyclic GMP as second messenger...
Article
Full-text available
Cardiac atrial natriuretic peptide (ANP) regulates arterial blood pressure, moderates cardiomyocyte growth, and stimulates angiogenesis and metabolism. ANP binds to the transmembrane guanylyl cyclase (GC) receptor, GC-A, to exert its diverse functions. This process involves a cGMP-dependent signaling pathway preventing pathological [Ca(2+)](i) incr...
Article
Full-text available
Atrial natriuretic peptide (ANP) and its guanylyl cyclase-A (GC-A) receptor are being involved in metabolism, although their role in the endocrine pancreas is still greatly unknown. The aim of this work is to study a possible role for the ANP/GC-A system in modulating pancreatic beta-cell function. The results presented here show a direct effect of...
Article
Full-text available
Atrial natriuretic peptide (ANP), via its guanylyl cyclase A (GC-A) receptor and intracellular guanosine 3′,5′-cyclic monophosphate production, is critically involved in the regulation of blood pressure. In patients with chronic heart failure, the plasma levels of ANP are increased, but the cardiovascular actions are severely blunted, indicating a...
Article
Atrial natriuretic peptide (ANP) via its guanylyl cyclase-A (GC-A) receptor participates in regulation of arterial blood pressure and vascular volume. Previous studies demonstrated that concerted renal diuretic/natriuretic and endothelial permeability effects of ANP cooperate in intravascular volume regulation. We show that the microvascular endoth...
Article
Full-text available
The ATP-sensitive potassium (K(ATP)) channel is a key molecule involved in glucose-stimulated insulin secretion. The activity of this channel regulates beta-cell membrane potential, glucose- induced [Ca(2+)](i) signals, and insulin release. In this study, the rapid effect of physiological concentrations of 17beta-estradiol (E2) on K(ATP) channel ac...
Article
Full-text available
Atrial (ANP) and B-type natriuretic peptides (BNP) modulate blood pressure and volume through the stimulation of cyclic GMP production by their guanylyl cyclase-A (GC-A) receptor. A novel isoform of GC-A has been identified that is the result of differential splicing of exon 4. The deletion of a 51-bp sequence is predicted to delete 17 amino acids...
Article
Full-text available
Atrial natriuretic peptide (ANP) regulates arterial blood pressure and volume. Its guanylyl cyclase-A (GC-A) receptor is expressed in vascular endothelium and mediates increases in cGMP, but the functional relevance is controversial. Notably, mice with endothelial-restricted GC-A deletion [EC GC-A knockout (KO) mice] exhibit significant chronic hyp...
Article
Tumor cells exhibit mechanisms by which chemotherapeutic drugs can be actively pumped out of the cell (e.g., p-glycoprotein pGP, MRP1), resulting in a multidrug resistant phenotype. Many human tumors show pronounced hypoxia which can result in a local ATP depletion which in turn may compromise the efficacy of these transporters. The aim of this stu...
Article
The cardiac hormones atrial and brain natriuretic peptides (NPs) counteract the systemic, hypertensive, and hypervolemic actions of angiotensin II (Ang II) via their guanylyl cyclase-A (GC-A) receptor. In the present study, we took advantage of genetically modified mice with conditional, cardiomyocyte (CM)-restricted disruption of GC-A (CM GC-A kno...
Article
Full-text available
The metabolic microenvironment of solid tumors is characterized by an oxygen deficiency and increased anaerobic glycolysis leading to extracellular acidosis and ATP depletion, which in turn may affect other energy-dependent cellular pathways. Since many tumors overexpress active drug transporters (e.g. the p-glycoprotein) leading to a multidrug-res...
Article
In the microenvironment of solid growing tumors, pronounced hypoxia or extracellular acidosis is commonly found. The aim of this study was the analysis of the cytotoxic effect of different chemotherapeutic agents (cisplatin, daunorubicin, docetaxel) under these conditions in vitro. Prostate carcinoma cells (R3327-AT1) were exposed to hypoxia (pO2 <...
Article
Full-text available
The expression and activity of P-glycoprotein (pGP) play a role in the multidrug resistance of tumors. Because solid-growing tumors often show pronounced hypoxia or extracellular acidosis, this study attempted to analyze the impact of an acidic environment on the expression and activity of pGP and on the cytotoxicity of chemotherapeutic agents. For...
Article
The steroid hormone aldosterone is a major regulator of extracellular volume and blood pressure. Aldosterone effectors are for example the epithelial Na(+) channel (ENaC), the Na(+)-K(+)-ATPase and the proximal tubule Na(+)/H(+) exchanger isoform 3 (NHE3). The aim of this study was to investigate whether aldosterone acts directly on proximal tubule...
Article
Cell migration is crucial for immune defence, wound healing or formation of tumour metastases. It has been shown that the activity of the Na(+)-H(+) exchanger (NHE1) plays an important role in cell migration. However, so far it is unknown whether Na(+)- HCO(3)(-) cotransport (NBC), which has similar functions in the regulation of intracellular pH (...
Article
Their glycolytic metabolism imposes an increased acid load upon tumour cells. The surplus protons are extruded by the Na+/H+ exchanger (NHE) which causes an extracellular acidification. It is not yet known by what mechanism extracellular pH (pHe) and NHE activity affect tumour cell migration and thus metastasis. We studied the impact of pHe and NHE...
Article
Full-text available
The steroid hormone aldosterone is important for salt and water homeostasis as well as for pathological tissue modifications in the cardiovascular system and the kidney. The mechanisms of action include a classical genomic pathway, but physiological relevant nongenotropic effects have also been described. Unlike for estrogens or progesterone, the m...
Article
The degree of albuminuria, the presence of sodium-dependent hypertension, and histological evidence of both tubular and interstitial pathology correlate with the progression of diabetic nephropathy. The sodium-hydrogen exchanger NHE-3 plays an integral role in both sodium reabsorption and receptor-mediated albumin endocytosis in proximal tubular ce...
Article
Full-text available
The epidermal growth factor (EGF) regulates cell proliferation, differentiation, and ion transport using ERK1/2 as a downstream effector. Furthermore, the EGF receptor (EGFR) is involved in signaling by G-protein-coupled receptors, growth hormone, and cytokines via transactivation. It has been suggested that steroids interact with peptide hormones....
Article
Full-text available
Receptor-mediated, clathrin-dependent endocytosis (RME) is important for macromolecular transport and regulation of cell-surface protein expression. Pharmacological studies have shown that the plasma membrane transport protein Na(+)/H(+) exchanger 3 (NHE3), which shuttles between the plasma membrane and the early endosomal compartment by means of c...
Article
Filtered proteins play a role in the pathogenesis of renal interstitial inflammation and fibrosis. At least part of these effects are mediated by the nuclear factor kappaB (NF-kappaB). Receptor-mediated endocytosis of proteins like albumin in renal proximal tubular cells is in part dependent on Na superset+/H superset+ exchanger (NHE) isoform 3. We...
Article
Albuminuria represents one of the most unfavourable diagnostic factors for the prognosis of nephropathies. We investigated albumin-induced NF-kappaB activation and the potential contribution of tyrosine kinase and protein kinase C. Therefore we exposed proximal tubule-derived human (IHKE-1), opossum (OK) and porcine (LLC-PK1) cell lines to serum al...
Article
Several studies support a role of filtered albumin in the pathogenesis of renal interstitial inflammation and fibrosis. At least, parts of these effects are mediated by the nuclear factor kappaB (NF-kappaB). Na+-H+ exchanger (NHE) isoform 3 supports receptor-mediated endocytosis of albumin in renal proximal tubular cells by a yet not completely und...
Article
Several studies support a role of filtered albumin in the pathogenesis of renal interstitial inflammation and fibrosis. At least, parts of these effects are mediated by the nuclear factor κB (NF-κB). Na+-H+ exchanger (NHE) isoform 3 supports receptor-mediated endocytosis of albumin in renal proximal tubular cells by a yet not completely understood...
Article
1. Receptor-mediated endocytosis is an important mechanism for transport of macromolecules and regulation of cell-surface receptor expression. In renal proximal tubules, receptor-mediated endocytosis mediates the reabsorption of filtered albumin. Acidification of the endocytic compartments is essential because it interferes with ligand-receptor dis...
Article
Previously, we showed that migration of transformed renal epithelial cells (MDCK-F cells) is a K&plus; channel-dependent process [J Clin Invest 1994;93:1631]. In order to determine whether K&plus; channel activity is a general requirement for locomotion, we extended our observations to NIH3T3 fibroblasts and human melanoma cells. Migration of both...
Article
Ochratoxin A (OTA) is a ubiquitous fungal metabolite with predominant nephrotoxic action. OTA impairs postproximal renal electrolyte handling and increases the incidence of renal adenoma and carcinoma. Furthermore, it is supposed to be involved in the pathogenesis of different forms of human renal diseases. Previously we have shown that OTA activat...
Article
Madin Darby canine kidney cells transformed by alkaline stress (MDCK-F cells) constitutively migrate at a rate of about 1 microm.min-1. Migration depends on the intermittent activity of a Ca2+-stimulated, 53-pS K+ channel (KCa channel) that is inhibitable by charybdotoxin. In the present study we examined whether this intermittent KCa channel activ...
Article
We investigated the effects of endothelin-1 (ET-1) on Madin-Darby canine kidney (MDCK) cells, a cell line originating from the renal collecting duct. The activity of transepithelial transport was assessed as the rate of dome formation in monolayers grown on solid support. The pH value of the dome fluid (dome pH) was measured by means of pH-selectiv...
Article
Similar to growth factors aldosterone stimulates Na+/H+ exchange in renal target cells leading to cytoplasmic alkalinization. An alkaline intracellular pH reduces the H+ bonds between repressor proteins and DNA leading to the destabilization of the nuclear chromatin. We observed that sustained alkaline stress "per se" can lead to malignant transfor...
Article
This chapter discusses the detailed description of the isolation and perfusion of the frog kidney, which has served for some years as a reliable experimental model in various studies. This chapter also focuses on a novel technique for fusing single epithelial cells to form giant cells. This experimental model could be a valuable tool for future res...
Article
The evaluation of the intracellular signal train and its regulatory function in controlling transepithelial transport with electrophysiological methods often requires intracellular measurements with microelectrodes. However, multiple impalements in epithelial cells are hampered by the small size of the cells. In an attempt to avoid these problems w...
Article
Aldosterone maintains acid-base balance and K+ homeostasis by controlling H+ and K+ secretion in renal epithelial cells. We have shown recently in the amphibian distal nephron that aldosterone activates a Na+/H+ exchange system in the luminal cell membrane, leading to transepithelial H+ secretion and cytoplasmic alkalinization. Since H+ secretory f...

Citations

... 5 Furthermore, intravital microscopy studies in mice have shown that ANP increases microvascular transendothelial albumin transport. 6 Vascular integrity depends upon inter endothelial cell junctions and the endothelial glycocalyx layer. The endothelial glycocalyx layer is composed of proteoglycans, glycoproteins, glycosaminoglycans (GAG) and associated plasma proteins. ...
... On the other hand, however, cardiomyocyte-specific overexpression of PDE5A recovered impaired cardiac functions from pressure overload and myocardial infarction (Pokreisz et al., 2009). Frantz and Kuhn et al. generated animals with cardiomyocyte-restricted deletion of PKG, and demonstrated the animals developed severe hypertrophy by chronic angiotensin II infusion or pressure overload (Frantz et al., 2013). Recently, we have consistently reported that sildenafil exhibited protective effects against cardiac hypertrophy via proliferator activated receptor γ co-activator-1α-PKG cascade (Zhu et al., 2021). ...
... Emerging evidence indicates that the cause of PE is associated with genetic factors since it was first expounded in the early 1960s [3,4]. Pregnant mice lacking catechol-O-methyltransferase, Corin, atrial natriuretic peptide, or Elabela exhibit a PE-like phenotype [5][6][7][8]. In humans, geneticists [9] suggested that a single gene may possibly be responsible for PE. ...
... A number of studies suggest that NUPs directly and indirectly affect glucose metabolism. Clinical studies revealed an increase in serum insulin level during the infusion of ANP [43]. The effect can be explained by a direct stimulating effect on the βcells. ...
... In HF, though Delrue et al. (43) had confirmed that SERPINA3 is still an independent predictor of all-cause mortality, studies have paid little attention to the effect of pharmacological treatment of DCM. Spironolactone (44)(45)(46)(47) dominates an important treated role in DCM. The The comparison of the 8 genes between dilated cardiomyopathy (DCM) and healthy in testing sets. ...
... Łączenie kaskad sygnałowych cyklicznych nukleotydów przez PDE3 jest dobrze scharakteryzowane w szlakach sygnałowych peptydów natriuretycznych. Zarówno receptory peptydów natriuretycznych [6], jak i izoforma PDE3B zakotwiczone są w błonie komórkowej w obrębie raft lipidowych zwanych kaweolami [40]. Ponieważ struktury te wprowadzają przedziałowość wewnątrz komórki, PDE3 uczestniczyć może także w odpowiedzi na inne czynniki zewnątrzkomórkowe, których receptory znajdują się w obrębie kaweoli [40]. ...
... Bones are shorter in mice and people with mutations that inactivate NPR2 (Bartels et al., 2004;Tamura et al., 2004;Tsuji and Kunieda, 2005;Khan et al., 2012;Geister et al., 2013;Nakao et al., 2015;Schmidt et al., 2018). Conversely bone length is increased by mutations that result in increased NPR2 activity in the absence of CNP (Miura et al., 2012(Miura et al., , 2014Hannema et al., 2013). ...
... In endothelial cells, cGMP accumulates in response to binding of atrial natriuretic peptide (ANP) to guanylyl cyclase-A (GC-A) or activation of eNOS [125][126][127][128][129] and can influence vascular permeability [114,130,131]. Inhibitors of phosphodiesterase 5 (PDE5) increase intracellular [cGMP] and are efficacious in the treatment of World Health Organization group 1 pulmonary arterial hypertension [132]. ...
... Na V Breast cancer [157] • Altering cytoskeletal elements to adopt cellular morphologies facilitative of migration • Promoting proteolytic degradation of the ECM K V Melanoma [158,159] Neuroblastoma [160] Breast cancer [161] • Interacting with β1-integrins to induce the membrane hyperpolarization preceding extensive cell dispersion and actin cytoskeleton reorganization • Modulating cell migration by allowing calcium entry and inducing rapid focal adhesion turnover rates GABA A R Breast cancer [162,163] Lung cancer [164] • Activating Akt and ERK1/2 kinases to facilitate downstream cellular migration pathways • Mediating upregulation of ECM-degrading metalloproteins nAChR Breast carcinoma [165] Cervical cancer [166] Facilitating nicotine-and growth factor-induced increases in redox regulator thioredoxin, overexpression of which induces: ...