ATP Receptor-Operated Ca2+ Influx and Catecholamine Release From Neuronal Cells

Physiology ◽  
1992 ◽  
Vol 7 (2) ◽  
pp. 56-59 ◽  
Author(s):  
K Inoue ◽  
K Nakazawa
Keyword(s):  
Mechanism Of Action ◽  
Physiological Function ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Extracellular Atp ◽  
Catecholamine Release ◽  
Cation Channels ◽  
Pc 12 Cells ◽  
P2 Purinoceptors

The physiological function of extracellular ATP was investigated using PC-12 cells as a model neuronal cell. The mechanism of action of ATP proposed is that ATP stimulates P2-purinoceptors, activates Ca2+-permeable cation channels, and causes Ca2+ influx, triggering catecholamine release.

scholarly journals Exosome-Mediated Activation of Neuronal Cells Triggered by γ-Aminobutyric Acid (GABA)

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2544
Author(s):  
Ryo Inotsuka ◽  
Miyako Udono ◽  
Atsushi Yamatsu ◽  
Mujo Kim ◽  
Yoshinori Katakura
Keyword(s):  
Oral Administration ◽  
Memory Function ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Aminobutyric Acid ◽  
Intestinal Cells ◽  
Cell Functions ◽  
Expression Of Genes

γ-Aminobutyric acid (GABA) is a potent bioactive amino acid, and several studies have shown that oral administration of GABA induces relaxation, improves sleep, and reduces psychological stress and fatigue. In a recent study, we reported that exosomes derived from GABA-treated intestinal cells serve as signal transducers that mediate brain–gut interactions. Therefore, the purpose of this study was to verify the functionality of GABA-derived exosomes and to examine the possibility of improving memory function following GABA administration. The results showed that exosomes derived from GABA-treated intestinal cells (Caco-2) activated neuronal cells (SH-SY5Y) by regulating genes related to neuronal cell functions. Furthermore, we found that exosomes derived from the serum of GABA-treated mice also activated SH-SY5Y cells, indicating that exosomes, which are capable of activating neuronal cells, circulate in the blood of mice orally administered GABA. Finally, we performed a microarray analysis of mRNA isolated from the hippocampus of mice that were orally administered GABA. The results revealed changes in the expression of genes related to brain function. Gene Set Enrichment Analysis (GSEA) showed that oral administration of GABA affected the expression of genes related to memory function in the hippocampus.

scholarly journals Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 250 ◽  
Author(s):  
Adel Alhazzani ◽  
Prasanna Rajagopalan ◽  
Zaher Albarqi ◽  
Anantharam Devaraj ◽  
Mohamed Hessian Mohamed ◽  
...  
Keyword(s):  
Cell Death ◽  
Transforming Growth Factor ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Apoptotic Cells ◽  
Sequence Of Events ◽  
Cox 2 ◽  
Anti Inflammatory

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-β, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-B and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-β, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-B and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro.

scholarly journals Haloperidol and Risperidone Induce Apoptosis Neuronal Cell : Invivo Study

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ester G Panserga ◽  
Cecep S Kristanto ◽  
Budi Pratiti ◽  
Patricia Wulandari
Keyword(s):  
Cell Apoptosis ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Total Percentage ◽  
White Rats ◽  
Male Wistar Rats ◽  
Group B

Abstract Introduction Antipsychotics are drugs that are widely prescribed for mental disorders, such as schizophrenia and psychosis. Recent in vitro studies show antipsychotics play a role in the initiation of neuronal cell apoptosis. This study aims to determine the effect of haloperidol and risperidone on neuronal cell apoptosis in Wistar white rats. Methods Male wistar rats aged 8 weeks (n = 30) were used in this study. Wistar rats were randomized into 6 groups. Group A: 5 wistar rats as a control without induced schizophrenia, aquades and drugs. Group B: 5 Wistar-induced psychotic mice (using 30 mg / kgBB ketamine, intraperitoneal injection for 5 days) and aquadest. Group C: 5 rats were induced psychotic and were given haloperidol or 0.05 mg / kgBB orally, for 28 days. Group D: 5 mice were induced psychotic and were given haloperidol 0.1 mg / kg orally, for 28 days. Group E: 5 mice were induced psychotic and were given risperidone 0.05 mg / kgBB orally, for 28 days. Group F: 5 mice were induced psychotic and given risperidone 0.1 mg / kgBB orally, for 28 days. Apoptosis of neuronal cells in the ventral tegmental area was assessed by caspase-3 immunohistochemistry. The colored area will be calculated as a total percentage using the imageJ program. Results Risperidone and haloperidol increase caspase-3 activity, but haloperidol increases caspase-3 activity more than risperidone. Conclussion Risperidone and haloperidol induce apoptosis of neuronal cells and tardive dyskinesia in Wistar rats with psychotic models.

scholarly journals Poliovirus Internal Ribosome Entry Segment Structure Alterations That Specifically Affect Function in Neuronal Cells: Molecular Genetic Analysis

2002 ◽  
Vol 76 (21) ◽  
pp. 10617-10626 ◽  
Author(s):  
Cécile E. Malnou ◽  
Tuija A. A. Pöyry ◽  
Richard J. Jackson ◽  
Katherine M. Kean
Keyword(s):  
Secondary Structure ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
In Vitro Translation ◽  
Internal Ribosome Entry ◽  
Cell Extracts ◽  
Internal Ribosome Entry Segment ◽  
Domain V ◽  
Bulge Loop

ABSTRACT Translation of poliovirus RNA is driven by an internal ribosome entry segment (IRES) present in the 5′ noncoding region of the genomic RNA. This IRES is structured into several domains, including domain V, which contains a large lateral bulge-loop whose predicted secondary structure is unclear. The primary sequence of this bulge-loop is strongly conserved within enteroviruses and rhinoviruses: it encompasses two GNAA motifs which could participate in intrabulge base pairing or (in one case) could be presented as a GNRA tetraloop. We have begun to address the question of the significance of the sequence conservation observed among enterovirus reference strains and field isolates by using a comprehensive site-directed mutagenesis program targeted to these two GNAA motifs. Mutants were analyzed functionally in terms of (i) viability and growth kinetics in both HeLa and neuronal cell lines, (ii) structural analyses by biochemical probing of the RNA, and (iii) translation initiation efficiencies in vitro in rabbit reticulocyte lysates supplemented with HeLa or neuronal cell extracts. Phenotypic analyses showed that only viruses with both GNAA motifs destroyed were significantly affected in their growth capacities, which correlated with in vitro translation defects. The phenotypic defects were strongly exacerbated in neuronal cells, where a temperature-sensitive phenotype could be revealed at between 37 and 39.5°C. Biochemical probing of mutated domain V, compared to the wild type, demonstrated that such mutations lead to significant structural perturbations. Interestingly, revertant viruses possessed compensatory mutations which were distant from the primary mutations in terms of sequence and secondary structure, suggesting that intradomain tertiary interactions could exist within domain V of the IRES.

scholarly journals Insulin Has Multiple Antiamyloidogenic Effects on Human Neuronal Cells

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 375-387 ◽  
Author(s):  
Giuseppe Pandini ◽  
Vincenza Pace ◽  
Agata Copani ◽  
Sebastiano Squatrito ◽  
Danilo Milardi ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Diabetic Patients ◽  
Cell Fractionation ◽  
Intracellular Accumulation ◽  
Insulin Degrading Enzyme ◽  
App Processing ◽  
Gsk 3Β ◽  
Human Neuronal Cells

Alzheimer’s disease is increased in diabetic patients. A defective insulin activity on the brain has been hypothesized to contribute to the neuronal cell dysregulation leading to AD, but the mechanism is not clear. We analyzed the effect of insulin on several molecular steps of amyloid precursor protein (APP) processing and β-amyloid (Aβ) intracellular accumulation in a panel of human neuronal cells and in human embryonic kidney 293 cells overexpressing APP-695. The data indicate that insulin, via its own receptor and the phosphatidylinositol-3-kinase/AKT pathway, influences APP phosphorylation at different sites. This rapid-onset, dose-dependent effect lasts many hours and mainly concerns dephosphorylation at the APP-T668 site. This effect of insulin was confirmed also in a human cortical neuronal cell line and in rat primary neurons. Cell fractionation and immunofluorescence studies indicated that insulin-induced APP-T668 dephosphorylation prevents the translocation of the APP intracellular domain fragment into the nucleus. As a consequence, insulin increases the transcription of antiamyloidogenic proteins such as the insulin-degrading enzyme, involved in Aβ degradation, and α-secretase. In contrast, the transcripts of pro-amyloidogenic proteins such as APP, β-secretase, and glycogen synthase kinase (Gsk)-3β are decreased. Moreover, cell exposure to insulin favors the nonamyloidogenic, α-secretase-dependent APP-processing pathway and reduces Aβ40 and Aβ42 intracellular accumulation, promoting their release in the extracellular compartment. The latter effects of insulin are independent of both Gsk-3β phosphorylation and APP-T668 dephosphorylation, as indicated by experiments with Gsk-3β inhibitors and with cells transfected with the nonphosphorylatable mutated APP-T668A analog. In human neuronal cells, therefore, insulin may prevent Aβ formation and accumulation by multiple mechanisms, both Gsk-3β dependent and independent.

scholarly journals Rapid Effects of Retinoic Acid on CREB and ERK Phosphorylation in Neuronal Cells

2004 ◽  
Vol 15 (12) ◽  
pp. 5583-5592 ◽  
Author(s):  
Estela Cañón ◽  
Jose Miguel Cosgaya ◽  
Sona Scsucova ◽  
Ana Aranda
Keyword(s):  
Retinoic Acid ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Primary Cultures ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Direct Stimulation ◽  
Creb Phosphorylation ◽  
Response Elements ◽  
Stimulation Of

Retinoic acid (RA) is a potent regulator of neuronal cell differentiation. RA normally activates gene expression by binding to nuclear receptors that interact with response elements (RAREs) in regulatory regions of target genes. We show here that in PC12 cell subclones in which the retinoid causes neurite extension, RA induces a rapid and sustained phosphorylation of CREB (cyclic AMP response element binding protein), compatible with a nongenomic effect. RA also causes a rapid increase of CREB phosphorylation in primary cultures of cerebrocortical cells and of dorsal root ganglia neurons from rat embryos. RA-mediated phosphorylation of CREB leads to a direct stimulation of CREB-dependent transcriptional activity and to activation of the expression of genes such as c-fos, which do not contain RAREs but contain cAMP response elements (CREs) in their promoters. CREB is a major target of extracellular signal regulated kinase ERK1/2 signaling in neuronal cells, and we demonstrate here that RA induces an early stimulation of ERK1/2, which is required both for CREB phosphorylation and transcriptional activity. These results demonstrate that RA, by a nongenomic mechanism, stimulates signaling pathways that lead to phosphorylation of transcription factors, which in turn activate the transcription of genes involved in neuronal differentiation.

scholarly journals PEDOT doped with algal, mammalian and synthetic dopants: polymer properties, protein and cell interactions, and influence of electrical stimulation on neuronal cell differentiation

2018 ◽  
Vol 6 (5) ◽  
pp. 1250-1261 ◽  
Author(s):  
P. J. Molino ◽  
L. Garcia ◽  
E. M. Stewart ◽  
M. Lamaze ◽  
B. Zhang ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Cell Differentiation ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Cell Interactions ◽  
Polymer Properties ◽  
Neuronal Cell Differentiation

PEDOT films were electrochemically polymerised with synthetic and biological dopants, characterised, and their interactions with proteins and neuronal cells investigated.

scholarly journals Progesterone induces the release of bull spermatozoa from oviductal epithelial cells

2019 ◽  
Vol 31 (9) ◽  
pp. 1463 ◽  
Author(s):  
J. Romero-Aguirregomezcorta ◽  
S. Cronin ◽  
E. Donnellan ◽  
S. Fair
Keyword(s):  
Epithelial Cells ◽  
Receptor Antagonist ◽  
Mechanism Of Action ◽  
Initial Dose ◽  
Inhibitory Action ◽  
Cumulus Cells ◽  
Optimum Concentration ◽  
Cation Channels ◽  
Bovine Oocyte ◽  
Bovine Spermatozoa

The mechanism that causes the detachment of spermatozoa from the oviductal reservoir around the time of ovulation remains to be elucidated. Because the cumulus cells of the bovine oocyte are known to secrete progesterone (P4), and P4 has been shown to act upon cation channels of spermatozoa (CatSper) in human spermatozoa, it was hypothesised that P4 could induce hyperactivation due to an influx of extracellular calcium, and this would facilitate detachment of spermatozoa from oviductal epithelial cells. Therefore, this study aimed to investigate the role and mechanism of action of P4 in the release of spermatozoa from bovine oviduct epithelial cells (BOEC). Initial dose–response assessments on sperm hyperactivation determined the optimum concentration of P4 (10 nM), mibefradil (a non-specific Ca2+ channel antagonist; 5µM), NNC 55-0396 dihydrochloride (NNC; a CatSper antagonist; 2µM), mifepristone (a classical and membrane P4 receptor antagonist; 400nM) and AG205 (a membrane P4 receptor antagonist; 10μM). BOEC explants were incubated with frozen–thawed bovine spermatozoa for 30min, following which loosely bound spermatozoa were removed. Two experiments were completed. In Experiment 1, BOECs were treated for 30min with either no treatment, P4, NNC, mibefradil, P4+mibefradil, P4+NNC, P4+mibefradil+NNC or P4+EGTA. In Experiment 2, BOECs were treated for 30min with either no treatment, P4, mifepristone, AG205, mifepristone+AG205, P4+mifepristone, P4+AG205 or P4+mifepristone+AG205. The number of spermatozoa remaining bound per millimetre squared of BOEC explant was determined. Progesterone stimulated the release of bound spermatozoa from BOEC explants, whereas NNC, mibefradil and EGTA inhibited this release. The release of spermatozoa by P4 was inhibited in the presence of both mifepristone and AG205, whereas the combination of both had the greatest inhibitory action on P4 release of spermatozoa. These findings suggest the presence of a P4 membrane receptor on bovine spermatozoa and that P4-induced release of spermatozoa from BOECs is likely mediated by extracellular Ca2+.

Intracellular redistribution of acetyl-CoA, the pivotal point in differential susceptibility of cholinergic neurons and glial cells to neurodegenerative signals

2014 ◽  
Vol 42 (4) ◽  
pp. 1101-1106 ◽  
Author(s):  
Andrzej Szutowicz ◽  
Hanna Bielarczyk ◽  
Anna Ronowska ◽  
Sylwia Gul-Hinc ◽  
Joanna Klimaszewska-Łata ◽  
...  
Keyword(s):  
Cell Viability ◽  
Pyruvate Dehydrogenase Complex ◽  
Neuronal Cells ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Cholinergic Neurons ◽  
Thiamine Pyrophosphate ◽  
Amyloid Β Peptide ◽  
Acetyl Coa ◽  
Dehydrogenase Complex

Intramitochondrial decarboxylation of glucose-derived pyruvate by PDHC (pyruvate dehydrogenase complex) is a principal source of acetyl-CoA, for mitochondrial energy production and cytoplasmic synthetic pathways in all types of brain cells. The inhibition of PDHC, ACO (aconitase) and KDHC (ketoglutarate dehydrogenase complex) activities by neurodegenerative signals such as aluminium, zinc, amyloid β-peptide, excess nitric oxide (NO) or thiamine pyrophosphate deficits resulted in much deeper losses of viability, acetyl-CoA and ATP in differentiated cholinergic neuronal cells than in non-differentiated cholinergic, and cultured microglial or astroglial cell lines. In addition, in cholinergic cells, such conditions caused inhibition of ACh (acetylcholine) synthesis and its quantal release. Furthermore, cholinergic neuronal cells appeared to be resistant to high concentrations of LPS (lipopolysaccharide). In contrast, in microglial cells, low levels of LPS caused severalfold activation of NO, IL-6 (interleukin 6) and TNFα (tumour necrosis factor α) synthesis/release, accompanied by inhibition of PDHC, KDHC and ACO activities, and suppression of acetyl-CoA, but relatively small losses in their ATP contents and viability parameters. Compounds that protected these enzymes against inhibitory effects of neurotoxins alleviated acetyl-CoA and ATP deficits, thereby maintaining neuronal cell viability. These data indicate that preferential susceptibility of cholinergic neurons to neurodegenerative insults may result from competition for acetyl-CoA between mitochondrial energy-producing and cytoplasmic ACh-synthesizing pathways. Such a hypothesis is supported by the existence of highly significant correlations between mitochondrial/cytoplasmic acetyl-CoA levels and cell viability/transmitter functions respectively.

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