scholarly journals The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

2018 ◽  
Vol 19 (10) ◽  
pp. 2962 ◽  
Author(s):  
Liliana Rytel
Keyword(s):  
Bisphenol A ◽  
Nerve Fibers ◽  
Double Immunofluorescence ◽  
Negative Effects ◽  
Protective Mechanisms ◽  
Neuregulin 1 ◽  
Small Doses ◽  
The Impact ◽  
First Time

Bisphenol A (BPA), a substance commonly used in the manufacture of plastics, shows multidirectional negative effects on humans and animals. Due to similarities to estrogens, BPA initially leads to disorders in the reproductive system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active substance which enhances the survivability of cells, inhibits apoptosis, and protects tissues against damaging factors. Because the influence of BPA on the nervous system has also been described, the aim of the present study was to investigate for the first time the influence of various doses of BPA on neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus using the routine single- and double-immunofluorescence technique. The obtained results have shown that BPA increases the number and affects the neurochemical characterization of NRG-1-LI in the uterus, and changes are visible even under the impact of small doses of this toxin. The character of observed changes depended on the dose of BPA and the part of the uterus studied. These observations suggest that NRG-1 in nerves supplying the uterus may play roles in adaptive and protective mechanisms under the impact of BPA.

scholarly journals Neuregulin 1 (NRG-1) as a neuronal active substance in the porcine intrahepatic nerve fibers in physiological conditions and under the influence of bisphenol A (BPA)

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Liliana Rytel ◽  
Marcelo Alarcón Lozano ◽  
Slawomir Gonkowski
Keyword(s):  
Bisphenol A ◽  
Liver Damage ◽  
Living Organism ◽  
Nerve Fibers ◽  
Neuregulin 1 ◽  
Physiological Conditions ◽  
High Doses ◽  
Oxide Synthase ◽  
The Impact ◽  
First Time

AbstractBisphenol A (BPA) is a substance commonly used in the production of plastics. Previous studies have described that it shows multidirectional harmful effects on the living organism. It is known that BPA causes liver damage, but knowledge about the roles of intrahepatic nerves in these mechanisms is extremely scanty. On the other hand, the exact roles of some neuronal substances in the nervous structures located in the liver still remain unknown. One of such substances, which is allocated a role in the stimulation of cell survival is neuregulin 1 (NRG-1). The aim of the present studies was to investigate the distribution of NRG-1 -like immunoreactive (NRG-1-LI) nerves in the liver in physiological conditions and under the influence of various doses of BPA using routine double immunofluorescence staining. The results (for the first time) show the presence of NRG-1 in the intrahepatic nerves, and co-localization of NGR-1 with neuronal isoform of nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP). Moreover, it has been observed that high doses of BPA increases the density of NRG-1-LI intrahepatic nerves and the degree of co-localization of NRG-1 with VIP. These observations suggest that NRG-1 located in intrahepatic nerves may play functions in processes connected with liver damage and/or regeneration under the impact of BPA.

scholarly journals Changes Caused by Low Doses of Bisphenol A (BPA) in the Neuro-Chemistry of Nerves Located in the Porcine Heart

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 780
Author(s):  
Krystyna Makowska ◽  
Slawomir Gonkowski
Keyword(s):  
Bisphenol A ◽  
Endocrine Disruptor ◽  
Sympathetic Innervation ◽  
Daily Intake ◽  
Everyday Objects ◽  
Living Organisms ◽  
The Impact ◽  
Heart Wall ◽  
Cholinergic Structures

Bisphenol A (BPA) contained in plastics used in the production of various everyday objects may leach from these items and contaminate food, water and air. As an endocrine disruptor, BPA negatively affects many internal organs and systems. Exposure to BPA also contributes to heart and cardiovascular system dysfunction, but many aspects connected with this activity remain unknown. Therefore, this study aimed to investigate the impact of BPA in a dose of 0.05 mg/kg body weight/day (in many countries such a dose is regarded as a tolerable daily intake–TDI dose of BPA–completely safe for living organisms) on the neurochemical characterization of nerves located in the heart wall using the immunofluorescence technique. The obtained results indicate that BPA (even in such a relatively low dose) increases the number of nerves immunoreactive to neuropeptide Y, substance P and tyrosine hydroxylase (used here as a marker of sympathetic innervation). However, BPA did not change the number of nerves immunoreactive to vesicular acetylcholine transporter (used here as a marker of cholinergic structures). These observations suggest that changes in the heart innervation may be at the root of BPA-induced circulatory disturbances, as well as arrhythmogenic and/or proinflammatory effects of this endocrine disruptor. Moreover, changes in the neurochemical characterization of nerves in the heart wall may be the first sign of exposure to BPA.

scholarly journals The Okur-Chung Neurodevelopmental Syndrome (OCNDS) mutation CK2K198R leads to a rewiring of kinase specificity

2021 ◽  
Author(s):  
Danielle M Caefer ◽  
Nhat Q Phan ◽  
Jennifer C Liddle ◽  
Jeremy L Balsbaugh ◽  
Joseph P O’Shea ◽  
...  
Keyword(s):  
High Resolution ◽  
Substrate Specificity ◽  
Tyrosine Phosphorylation ◽  
Initial Step ◽  
Loss Of Function ◽  
Scoring Method ◽  
Disease Condition ◽  
The Impact ◽  
First Time

AbstractOkur-Chung Neurodevelopmental Syndrome (OCNDS) is caused by heterozygous mutations to the CSNK2A1 gene, which encodes the alpha subunit of casein kinase II (CK2). The most frequently occurring mutation is lysine 198 to arginine (K198R). To investigate the impact of this mutation, we first generated a high-resolution phosphorylation motif of CK2WT, including the first characterization of specificity for tyrosine phosphorylation activity. A second high resolution motif representing CK2K198R substrate specificity was also generated. Here we report for the first time the impact of the OCNDS associated CK2K198R mutation. Contrary to prior speculation, the mutation does not result in a loss of function, but rather shifts the substrate specificity of the kinase. Broadly speaking the mutation leads to 1) a decreased preference for acidic residues in the +1 position, 2) a decreased preference for threonine phosphorylation, 3) an increased preference for tyrosine phosphorylation, and 4) an alteration of the tyrosine phosphorylation specificity motif. To further investigate the result of this mutation we have developed a probability-based scoring method, allowing us to predict shifts in phosphorylation in the K198R mutant relative to the wild type kinase. As an initial step we have applied the methodology to the set of axonally localized ion channels in an effort to uncover potential alterations of the phosphoproteome associated with the OCNDS disease condition.

Characterization of transport mechanisms and determinants critical for Na+-dependent Pisymport of the PiT family paralogs human PiT1 and PiT2

2006 ◽  
Vol 291 (6) ◽  
pp. C1377-C1387 ◽  
Author(s):  
Pernille Bøttger ◽  
Susanne E. Hede ◽  
Morten Grunnet ◽  
Boy Høyer ◽  
Dan A. Klærke ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Divalent Cations ◽  
Maximal Activity ◽  
Xenopus Laevis Oocytes ◽  
Transport Function ◽  
Knockout Mutant ◽  
Uptake Medium ◽  
The Impact ◽  
First Time

The general phosphate need in mammalian cells is accommodated by members of the Pitransport (PiT) family ( SLC20), which use either Na+or H+to mediate inorganic phosphate (Pi) symport. The mammalian PiT paralogs PiT1 and PiT2 are Na+-dependent Pi(NaPi) transporters and are exploited by a group of retroviruses for cell entry. Human PiT1 and PiT2 were characterized by expression in Xenopus laevis oocytes with32Pias a traceable Pisource. For PiT1, the Michaelis-Menten constant for Piwas determined as 322.5 ± 124.5 μM. PiT2 was analyzed for the first time and showed positive cooperativity in Piuptake with a half-maximal activity constant for Piof 163.5 ± 39.8 μM. PiT1- and PiT2-mediated Na+-dependent Piuptake functions were not significantly affected by acidic and alkaline pH and displayed similar Na+dependency patterns. However, only PiT2 was capable of Na+-independent Pitransport at acidic pH. Study of the impact of divalent cations Ca2+and Mg2+revealed that Ca2+was important, but not critical, for NaPitransport function of PiT proteins. To gain insight into the NaPicotransport function, we analyzed PiT2 and a PiT2 Pitransport knockout mutant using22Na+as a traceable Na+source. Na+was transported by PiT2 even without Piin the uptake medium and also when Pitransport function was knocked out. This is the first time decoupling of Pifrom Na+transport has been demonstrated for a PiT family member. Moreover, the results imply that putative transmembrane amino acids E55and E575are responsible for linking Piimport to Na+transport in PiT2.

scholarly journals Bisphenol A (BPA) Affects the Enteric Nervous System in the Porcine Stomach

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2445
Author(s):  
Krystyna Makowska ◽  
Sławomir Gonkowski
Keyword(s):  
Nervous System ◽  
Bisphenol A ◽  
Enteric Nervous System ◽  
Gastric Wall ◽  
Cholinergic Neurons ◽  
Double Immunofluorescence ◽  
Adaptive Processes ◽  
Living Organisms ◽  
The Impact ◽  
Myenteric Ganglia

Bisphenol A (BPA) is widely utilized in plastic production process all over the world. Previous studies have shown that BPA, with its similarity to estrogen, may negatively affect living organisms. It is acknowledged that BPA distorts the activity of multiple internal systems, including the nervous, reproductive, urinary, and endocrine systems. BPA also affects the gastrointestinal tract and enteric nervous system (ENS), which is placed throughout the wall from the esophagus to the rectum. Contrary to the intestine, the influence of BPA on the ENS in the stomach is still little known. This study, performed using the double immunofluorescence method, has revealed that BPA affects the number of nervous structures in the porcine gastric wall immunoreactive to vesicular acetylcholine transporter (VAChT, a marker of cholinergic neurons), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL) and cocaine- and amphetamine-regulated transcript peptide (CART). The character and severity of noted alterations depended on the part of the ENS, the BPA dose, and the type of neuronal substance. Administration of BPA resulted in an increase in the number of nervous structures containing SP, GAL, and/or CART, and a decrease in the number of cholinergic neurons in all parts of the gastric wall. The number of VIP-positive nervous structures increased in the enteric myenteric ganglia, along with the muscular and mucosal layers, whilst it decreased in the submucous ganglia. The exact mechanism of noted changes was not absolutely obvious, but they were probably related to the neuroprotective and adaptive processes constituting the response to the impact of BPA.

scholarly journals Root Proteomic Analysis of Two Grapevine Rootstock Genotypes Showing Different Susceptibility to Salt Stress

2020 ◽  
Vol 21 (3) ◽  
pp. 1076 ◽  
Author(s):  
Bhakti Prinsi ◽  
Osvaldo Failla ◽  
Attilio Scienza ◽  
Luca Espen
Keyword(s):  
Salt Stress ◽  
Abiotic Stress ◽  
Energy Metabolism ◽  
Agricultural Soils ◽  
Agricultural Practices ◽  
Limiting Factor ◽  
Protective Mechanisms ◽  
Biochemical Level ◽  
The Impact ◽  
First Time

Salinity represents a very limiting factor that affects the fertility of agricultural soils. Although grapevine is moderately susceptible to salinity, both natural causes and agricultural practices could worsen the impact of this abiotic stress. A promising possibility to reduce this problem in vineyards is the use of appropriate graft combinations. The responses of grapevine rootstocks to this abiotic stress at the root level still remain poorly investigated. In order to obtain further information on the multifaceted responses induced by salt stress at the biochemical level, in the present work we analyzed the changes that occurred under control and salt conditions in the root proteomes of two grapevine rootstock genotypes, M4 and 101.14. Moreover, we compared the results considering that M4 and 101.14 were previously described to have lower and higher susceptibility to salt stress, respectively. This study highlighted the greater capability of M4 to maintain and adapt energy metabolism (i.e., synthesis of ATP and NAD(P)H) and to sustain the activation of salt-protective mechanisms (i.e., Na sequestration into the vacuole and synthesis of osmoprotectant compounds). Comparitively, in 101.14 the energy metabolism was deeply affected and there was an evident induction of the enzymatic antioxidant system that occurred, pointing to a metabolic scenario typical of a suffering tissue. Overall, this study describes for the first time in grapevine roots some of the more crucial events that characterize positive (M4) or negative (101.14) responses evoked by salt stress conditions.

scholarly journals The Neurochemical Characterization of Parasympathetic Nerve Fibers in the Porcine Uterine Wall Under Physiological Conditions and After Exposure to Bisphenol A (BPA)

2019 ◽  
Vol 35 (4) ◽  
pp. 867-882 ◽  
Author(s):  
Rytel Liliana ◽  
Gonkowski Slawomir ◽  
Janowski Tomasz ◽  
Wojtkiewicz Joanna ◽  
Pomianowski Andrzej
Keyword(s):  
Bisphenol A ◽  
Uterine Wall ◽  
Nerve Fibers ◽  
Parasympathetic Nerve ◽  
Physiological Conditions

scholarly journals Comparison of the In Vitro and Ex Vivo Permeation of Existing Topical Formulations Used in the Treatment of Facial Angiofibroma and Characterization of the Variations Observed

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1060
Author(s):  
Guillaume Le Guyader ◽  
Bernard Do ◽  
Victoire Vieillard ◽  
Karine Andrieux ◽  
Muriel Paul
Keyword(s):  
Ex Vivo ◽  
Thermodynamic Activity ◽  
Physico Chemical ◽  
Ex Vivo Permeation ◽  
Franz Cells ◽  
Great Heterogeneity ◽  
The Impact ◽  
First Time

Rapamycin has been used topically to treat facial angiofibromas associated with tuberous sclerosis for more than a decade. In the absence of a commercial form, a large number of formulations have been clinically tested. However, given the great heterogeneity of these studies, particularly with regard to the response criteria, it was difficult to know the impact and thus to compare the relevance of the formulations used. The objective of this work was therefore to evaluate the link between the diffusion of rapamycin and the physico-chemical characteristics of these different formulations on Strat-M® membranes as well as on human skin using Franz cells. Our results underline the importance of the type of vehicle used (hydrogel > cream > lipophilic ointment), the soluble state of rapamycin and its concentration close to saturation to ensure maximum thermodynamic activity. Thus, this is the first time that a comparative study of the different rapamycin formulations identified in the literature for the management of facial angiofibromas has been carried out using a pharmaceutical and biopharmaceutical approach. It highlights the important parameters to be considered in the development and optimization of topical rapamycin formulations with regard to cutaneous absorption for clinical efficacy.

scholarly journals Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3973
Author(s):  
Nicole Chmielewski-Stivers ◽  
Benoit Petit ◽  
Jonathan Ollivier ◽  
Virginie Monceau ◽  
Pelagia Tsoutsou ◽  
...  
Keyword(s):  
Radiation Toxicity ◽  
Protective Mechanisms ◽  
Molecular Determinant ◽  
Organ Specific ◽  
Radiotherapy Toxicity ◽  
The Impact ◽  
First Time ◽  
Paclitaxel Treatment

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female wild-type (WT) mice were treated with paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB-deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones, including estrogen. In females, RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by paclitaxel but enhanced cardiac sensitivity to radiotherapy. Conversely, rhoB-deficiency protected males from radiation toxicity. In sum, RhoB was identified as a molecular determinant driving estrogen-dependent cardioprotection in female mice, whereas neuroprotection was not sex hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

scholarly journals The Influence of Bisphenol A (BPA) on the Occurrence of Selected Active Substances in Neuregulin 1 (NRG1)-Positive Enteric Neurons in the Porcine Large Intestine

2021 ◽  
Vol 22 (19) ◽  
pp. 10308
Author(s):  
Krystyna Makowska ◽  
Kamila Szymańska ◽  
Jarosław Całka ◽  
Sławomir Gonkowski
Keyword(s):  
Bisphenol A ◽  
Enteric Neurons ◽  
Neuregulin 1 ◽  
Enteric Plexus ◽  
Other Substances ◽  
Intestinal Functions ◽  
Living Organisms ◽  
Oxide Synthase ◽  
The Impact ◽  
Active Substances

Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances.

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