scholarly journals Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Daniela Giovannini ◽  
Federica Andreola ◽  
Paola Spitalieri ◽  
Ewa Krystyna Krasnowska ◽  
Arianna Colini Baldeschi ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Primary Cultures ◽  
In Vitro Models ◽  
Neural Population ◽  
Symptomatic Therapy ◽  
Brain Functions ◽  
Dopaminergic Differentiation

AbstractOver the last 20 years, the efforts to develop new therapies for Parkinson’s disease (PD) have focused not only on the improvement of symptomatic therapy for motor and non-motor symptoms but also on the discovering of the potential causes of PD, in order to develop disease-modifying treatments. The emerging role of dysregulation of the Wnt/β-catenin signaling in the onset and progression of PD, as well as of other neurodegenerative diseases (NDs), renders the targeting of this signaling an attractive therapeutic opportunity for curing this brain disorder. The natriuretic peptides (NPs) atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are cardiac and vascular-derived hormones also widely expressed in mammalian CNS, where they seem to participate in numerous brain functions including neural development/differentiation and neuroprotection. We recently demonstrated that ANP affects the Wnt/β-catenin pathway possibly through a Frizzled receptor-mediated mechanism and that it acts as a neuroprotective agent in in vitro models of PD by upregulating this signaling. Here we provide further evidence supporting the therapeutic potential of this class of natriuretic hormones. Specifically, we demonstrate that all the three natriuretic peptides are neuroprotective for SHSY5Y cells and primary cultures of DA neurons from mouse brain, subjected to neurotoxin insult with 6-hydroxydopamine (6-OHDA) for mimicking the neurodegeneration of PD, and these effects are associated with the activation of the Wnt/β-catenin pathway. Moreover, ANP, BNP, CNP are able to improve and accelerate the dopaminergic differentiation and maturation of hiPSCs-derived neural population obtained from two differed healthy donors, concomitantly affecting the canonical Wnt signaling. Our results support the relevance of exogenous ANP, BNP, and CNP as attractive molecules for both neuroprotection and neurorepair in PD, and more in general, in NDs for which aberrant Wnt signaling seems to be the leading pathogenetic mechanism.

Effects of natriuretic peptides and nitroprusside on venous function in trout

1997 ◽  
Vol 273 (2) ◽  
pp. R527-R539 ◽  
Author(s):  
K. R. Olson ◽  
D. J. Conklin ◽  
A. P. Farrell ◽  
J. E. Keen ◽  
Y. Takei ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Aortic Pressure ◽  
Systemic Resistance ◽  
Venous Compliance ◽  
Venous Capacitance ◽  
Unstressed Volume ◽  
Ventral Aorta

Active venous regulation of cardiovascular function is well known in mammals but has not been demonstrated in fish. In the present studies, the natriuretic peptides (NP) rat atrial natriuretic peptide (ANP) and trout ventricular natriuretic peptide (VNP), clearance receptor inhibitor SC-46542, and sodium nitroprusside (SNP) were infused into unanesthetized trout fitted with pressure cannulas in the ventral aorta, dorsal aorta, and ductus Cuvier, and a ventral aorta (VA) flow probe was used to measure cardiac output (CO). In another group, in vivo vascular (venous) capacitance curves were obtained during ANP or SNP infusion. The in vitro effects of NP on vessels and the heart were also examined. ANP, VNP, and SC-46542 decreased central venous pressure (PVen), CO, stroke volume (SV), and gill resistance (RG), whereas systemic resistance (RS) and heart rate (HR) increased. Dorsal aortic pressure (PDA) transiently increased and then fell even though RS remained elevated. ANP decreased mean circulatory filling pressure (MCFP), increased vascular compliance at all blood volumes, and increased unstressed volume in hypovolemic fish. ANP had no direct effect on the heart. ANP responses in vivo were not altered in trout made hypotensive by prior treatment with the angiotensin-converting enzyme inhibitor lisinopril. SNP reduced ventral aortic pressure (PVA), PDA, and RS, increased CO and HR, but did not affect PVen, SV, or RG. SNP slightly decreased MCFP but did not affect compliance or unstressed volume. In vitro, large systemic arteries were more responsive than veins to NP, whereas SNP relaxed both. These results show that, in vivo, NP decrease venous compliance, thereby decreasing venous return, CO, and arterial pressure. Conversely, SNP hypotension is due to decreased RS. This is the first evidence for active regulation of venous capacitance in fish, which probably occurs in small veins or venules. The presence of venous baroreceptors is also suggested.

Natriuretic peptides inhibit rat astroglial proliferation: mediation by C receptor

1991 ◽  
Vol 261 (2) ◽  
pp. R453-R457 ◽  
Author(s):  
E. R. Levin ◽  
H. J. Frank
Keyword(s):  
Growth Factor ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Thymidine Incorporation ◽  
Primary Cultures ◽  
Physiological Role ◽  
Brain Cell ◽  
Bovine Brain ◽  
High Affinity ◽  
Capillary Endothelial Cells

The processing and secretion of atrial natriuretic peptide (ANP) from neurons and the expression of high-affinity receptors on astroglia from primary cultures of fetal rat diencephalon have recently been demonstrated. Thus natriuretic peptides may play a role in neuronal-glial signaling, but a physiological role has not been characterized. In these studies, we show that ANP and brain natriuretic peptide significantly (P less than 0.05) decrease the incorporation of [3H]thymidine into astroglia in the presence of fetal bovine serum and inhibit the proliferation of these cells in the presence or absence of serum. These effects were evident at concentrations of natriuretic peptides (10(-10) M) characteristic of the receptor Kd and were not seen in cultured bovine brain capillary endothelial cells, another brain cell expressing high-affinity receptors for the natriuretic peptides. The antiproliferative effects were potently produced by ANP-(4-23), a ring-deleted analogue of ANP-(1-28), which at the concentrations used in this study binds only to the C or low-molecular-weight natriuretic peptide receptor. Thymidine incorporation was not affected by adenosine 3',5'-cyclic monophosphate (cAMP), the inhibition of which has been proposed to mediate postbinding signaling of the C receptor. Epidermal growth factor (10(-9) M) produced an 87% increase in thymidine incorporation, which was not significantly inhibited by either form of ANP. Thus natriuretic peptides in the brain may serve as antigrowth factors for glia through binding to a receptor previously felt to function solely in peptide clearance. The inhibitory effects are not the result of inhibiting the proliferative effects of an endogenous growth factor and are cAMP independent.

scholarly journals Anti-inflammatory activity of Wnt signaling in enteric nervous system: in vitro preliminary evidences in rat primary cultures

2015 ◽  
Vol 12 (1) ◽  
pp. 23 ◽  
Author(s):  
Rosa Di Liddo ◽  
Thomas Bertalot ◽  
Anne Schuster ◽  
Sandra Schrenk ◽  
Alessia Tasso ◽  
...  
Keyword(s):  
Nervous System ◽  
Wnt Signaling ◽  
Enteric Nervous System ◽  
Primary Cultures ◽  
Inflammatory Activity ◽  
Anti Inflammatory

scholarly journals C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice

2021 ◽  
Vol 22 (16) ◽  
pp. 8966
Author(s):  
Guofang Shen ◽  
Shirley Hu ◽  
Zhen Zhao ◽  
Lubo Zhang ◽  
Qingyi Ma
Keyword(s):  
Brain Injury ◽  
Natriuretic Peptide ◽  
Glucose Deprivation ◽  
In Vitro Models ◽  
Neurological Deficits ◽  
Vascular Protection ◽  
The Brain

C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.

scholarly journals In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OΔN89β-catenin system

Oncogene ◽  
2012 ◽  
Vol 32 (7) ◽  
pp. 883-893 ◽  
Author(s):  
T Jardé ◽  
R J Evans ◽  
K L McQuillan ◽  
L Parry ◽  
G J Feng ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
In Vitro Models ◽  
Therapeutic Targeting

Evaluation of renal in vitro models used in ochratoxin research

2016 ◽  
Vol 9 (3) ◽  
pp. 435-454
Author(s):  
A.H. Heussner ◽  
T. Paget
Keyword(s):  
Cell Model ◽  
Primary Cultures ◽  
In Vitro Models ◽  
Cellular Target ◽  
Proximal Tubular ◽  
A Cell ◽  
S3 Segment ◽  
Renal Proximal Tubular ◽  
Tissue Alterations

Ochratoxin A (OTA) induces renal carcinomas in rodents with a specific localisation in the S3 segment of proximal tubules and distinct early severe tissue alterations, which have been observed also in other species. Pronounced species- and sex-specific differences in toxicity occur and similar effects cannot be excluded in humans, however precise mechanism(s) remain elusive until today. In such cases, the use of in vitro models for mechanistic investigations can be very useful; in particular if a non-genotoxic mechanism of cancer formation is assumed which include cytotoxic effects. However, potential genotoxic mechanisms can also be investigated in vitro. A crucial issue of in vitro research is the choice of the appropriate cell model. Apparently, the cellular target of OTA is the renal proximal tubular cell; therefore cells from this tissue area are the most reasonable model. Furthermore, cells from affected species should be used and can be compared to cells of human origin. Another important parameter is whether to use primary cultures or to choose a cell line from the huge variety of cell lines available. In any case, important characteristics and quality controls need to be verified beforehand. Therefore, this review discusses the renal in vitro models that have been used for the investigation of renal ochratoxin toxicity. In particular, we discuss the choice of the models and the essential parameters making them suitable models for ochratoxin research together with exemplary results from this research. Furthermore, new promising models such as hTERT-immortalised cells and 3D-cultures are briefly discussed.

A C TYPE NATRIURETIC PEPTIDE IS A VASODILATOR IN VIVO AND IN VITRO IN THE COMMON DOGFISH

1992 ◽  
Vol 133 (2) ◽  
pp. R1-R4 ◽  
Author(s):  
C. Bjenning ◽  
Y. Takei ◽  
T.X. Watanabe ◽  
K. Nakajima ◽  
S. Sakakibara ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Physiological Role ◽  
Arterial Blood ◽  
Brain Natriuretic Peptides ◽  
Dose Dependent

ABSTRACT The effects of an elasmbranch cardiac C-type natriuretic peptide (dogfish CNP-22) on arterial blood pressure were investigated in vivo in chronically cannulated dogfish Scyliorhinus canicula and in vitro by a myographic technique using the distal part of the first branchial artery. In-vivo dogfish CNP-22 caused a dose-dependent reduction in mean arterial blood pressure which was much more potent than that of α-human ANP. In-vitro dogfish CNP-22 also caused a dose-dependent relaxation which was independent of the endothelium. These results are in marked contrast to those obtained in similar studies on other vertebrate species in which CNP exhibited only mild hypotensive effects compared to both atrial and brain natriuretic peptides. This study indicates the importance of using homologous peptides in determing the physiological role of natriuretic peptides in non-mammalian vertebrates.

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