scholarly journals Proteomic Identification of Binding Partners for the Brain Metabolite Lanthionine Ketimine (LK) and Documentation of LK Effects on Microglia and Motoneuron Cell Cultures

2010 ◽  
Vol 30 (8) ◽  
pp. 2979-2988 ◽  
Author(s):  
K. Hensley ◽  
A. Christov ◽  
S. Kamat ◽  
X. C. Zhang ◽  
K. W. Jackson ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Binding Partners ◽  
Brain Metabolite ◽  
Proteomic Identification ◽  
The Brain ◽  
Motoneuron Cell

scholarly journals Clozapine Prevents Poly (I:C) Induced Inflammation by Modulating NLRP3 Pathway in Microglial Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 577
Author(s):  
Vijayasree V. Giridharan ◽  
Giselli Scaini ◽  
Gabriela D. Colpo ◽  
Tejaswini Doifode ◽  
Omar F. Pinjari ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Nlrp3 Inflammasome ◽  
Antipsychotic Drugs ◽  
Poly I:C ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Primary Microglial Cell ◽  
Anti Inflammatory ◽  
The Brain ◽  
Nlrp3 Expression

Schizophrenia is a complex psychiatric disorder that exhibits an interconnection between the immune system and the brain. Experimental and clinical studies have suggested the presence of neuroinflammation in schizophrenia. In the present study, the effect of antipsychotic drugs, including clozapine, risperidone, and haloperidol (10, 20 and 20 μM, respectively), on the production of IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IL-18, INF-γ, and TNF-α was investigated in the unstimulated and polyriboinosinic-polyribocytidilic acid [poly (I:C)]-stimulated primary microglial cell cultures. In the unstimulated cultures, clozapine, risperidone, and haloperidol did not influence the cytokine levels. Nevertheless, in cell cultures under strong inflammatory activation by poly (I:C), clozapine reduced the levels of IL-1α, IL-1β, IL-2, and IL-17. Risperidone and haloperidol both reduced the levels of IL-1α, IL-1β, IL-2, and IL-17, and increased the levels of IL-6, IL-10, INF-γ, and TNF-α. Based on the results that were obtained with the antipsychotic drugs and observing that clozapine presented with a more significant anti-inflammatory effect, clozapine was selected for the subsequent experiments. We compared the profile of cytokine suppression obtained with the use of NLRP3 inflammasome inhibitor, CRID3 to that obtained with clozapine, to test our hypothesis that clozapine inhibits the NLRP3 inflammasome. Clozapine and CRID3 both reduced the IL-1α, IL-1β, IL-2, and IL-17 levels. Clozapine reduced the level of poly (I:C)-activated NLRP3 expression by 57%, which was higher than the reduction thay was seen with CRID3 treatment (45%). These results suggest that clozapine might exhibit anti-inflammatory effects by inhibiting NLRP3 inflammasome and this activity is not typical with the use of other antipsychotic drugs under the conditions of strong microglial activation.

scholarly journals The Brain Metabolite Kynurenic Acid Inhibits α7 Nicotinic Receptor Activity and Increases Non-α7 Nicotinic Receptor Expression: Physiopathological Implications

2001 ◽  
Vol 21 (19) ◽  
pp. 7463-7473 ◽  
Author(s):  
Corey Hilmas ◽  
Edna F. R. Pereira ◽  
Manickavasagom Alkondon ◽  
Arash Rassoulpour ◽  
Robert Schwarcz ◽  
...  
Keyword(s):  
Nicotinic Receptor ◽  
Kynurenic Acid ◽  
Receptor Expression ◽  
Receptor Activity ◽  
Brain Metabolite ◽  
The Brain

scholarly journals Boosting GSH Using the Co-Drug Approach: I-152, a Conjugate of N-acetyl-cysteine and β-mercaptoethylamine

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1291 ◽  
Author(s):  
Rita Crinelli ◽  
Carolina Zara ◽  
Michaël Smietana ◽  
Michele Retini ◽  
Mauro Magnani ◽  
...  
Keyword(s):  
Cell Cultures ◽  
In Vivo Studies ◽  
In Vivo Metabolism ◽  
Pharmacokinetic Properties ◽  
Immunomodulatory Properties ◽  
Acetyl Cysteine ◽  
High Doses ◽  
The Brain

Glutathione (GSH) has poor pharmacokinetic properties; thus, several derivatives and biosynthetic precursors have been proposed as GSH-boosting drugs. I-152 is a conjugate of N-acetyl-cysteine (NAC) and S-acetyl-β-mercaptoethylamine (SMEA) designed to release the parent drugs (i.e., NAC and β-mercaptoethylamine or cysteamine, MEA). NAC is a precursor of L-cysteine, while MEA is an aminothiol able to increase GSH content; thus, I-152 represents the very first attempt to combine two pro-GSH molecules. In this review, the in-vitro and in-vivo metabolism, pro-GSH activity and antiviral and immunomodulatory properties of I-152 are discussed. Under physiological GSH conditions, low I-152 doses increase cellular GSH content; by contrast, high doses cause GSH depletion but yield a high content of NAC, MEA and I-152, which can be used to resynthesize GSH. Preliminary in-vivo studies suggest that the molecule reaches mouse organs, including the brain, where its metabolites, NAC and MEA, are detected. In cell cultures, I-152 replenishes experimentally depleted GSH levels. Moreover, administration of I-152 to C57BL/6 mice infected with the retroviral complex LP-BM5 is effective in contrasting virus-induced GSH depletion, exerting at the same time antiviral and immunomodulatory functions. I-152 acts as a pro-GSH agent; however, GSH derivatives and NAC cannot completely replicate its effects. The co-delivery of different thiol species may lead to unpredictable outcomes, which warrant further investigation.

Growth characteristics in cell culture and pathogenicity in mice of two terrestrial rabies strains indigenous to Canada

1988 ◽  
Vol 34 (1) ◽  
pp. 19-23 ◽  
Author(s):  
W. A. Webster ◽  
K. M. Charlton ◽  
G. A. Casey
Keyword(s):  
Cell Culture ◽  
Cell Cultures ◽  
Culture Supernatant ◽  
Neuroblastoma Cell ◽  
Cell Types ◽  
Kidney Cells ◽  
Baby Hamster Kidney Cell ◽  
Baby Hamster Kidney ◽  
The Brain ◽  
Baby Hamster Kidney Cells

Two strains of street rabies virus from striped skunks (Mephitis mephitis) were used to infect either a murine neuroblastoma (NA 1300) or a baby hamster kidney (BHK-21/C13) cell culture and the cell infection rates were noted during 4 days postinfection. These cultures were then passaged for four consecutive passages, and the viruses obtained in the supernatant fluids of passage 4 were then treated as original isolates and used to infect both neuroblastoma and baby hamster kidney cells. The mortality period in Swiss white mice caused by the various virus suspensions was noted. The virus strain from the brain of skunks from Saskatchewan infected neuroblastoma and baby hamster kidney cells equally well, produced similar virus titres in supernatant fluids after four subcultures in both cell types, and appeared to produce similar mortality periods in mice from either the original brain tissue or from cell culture supernatant fluids. On the other hand, the virus from the brains of skunks from Ontario readily infected neuroblastoma but poorly infected baby hamster kidney cell cultures. Passage of this strain through four subcultures in both cell types produced virus titres in the supernatant fluids of equal magnitude. However, reisolation of the virus from the supernatant fluid of passage 4 in neuroblastoma cell cultures showed a similar pattern to that from the original brain, while the virus from baby hamster kidney cell passage supernatant fluid was considerably altered. Although the mortality period in mice was similar with virus from the brain and neuroblastoma cell cultures, this period was shortened when mice were inoculated with baby hamster kidney culture supernatant virus. Virus from the salivary glands of Ontario skunks readily infected both cell types, producing similar titres at 4 days postinfection. The mortality period of mice inoculated with salivary gland suspensions was shorter than of those inoculated with brain suspensions. These findings demonstrate differences in rabies street virus strains that may have affected diagnostic procedures.

65 Detection of presenilin I protein in the brain and primary mesencephalic cell cultures

1996 ◽  
Vol 17 (4) ◽  
pp. S17
Author(s):  
N. Tezapsidis ◽  
J.M. Johnston ◽  
J. Shioi ◽  
H.-C. Li ◽  
G.A. Elder
Keyword(s):  
Cell Cultures ◽  
The Brain

Neurotoxicant-induced inflammatory response in three-dimensional brain cell cultures

2007 ◽  
Vol 26 (4) ◽  
pp. 339-346 ◽  
Author(s):  
F. Monnet-Tschudi ◽  
M-G. Zurich ◽  
P. Honegger
Keyword(s):  
Inflammatory Response ◽  
Cell Cultures ◽  
Neuronal Damage ◽  
Brain Cell ◽  
Brain Inflammation ◽  
Cellular Interactions ◽  
Cns Injury ◽  
Brain Cell Cultures ◽  
The Brain ◽  
Glial Reactivity

Brain inflammatory response is triggered by the activation of microglial cells and astrocytes in response to various types of CNS injury, including neurotoxic insults. Its outcome is determined by cellular interactions, inflammatory mediators, as well as trophic and/or cytotoxic signals, and depends on many additional factors such as the intensity and duration of the insult, the extent of both the primary neuronal damage and glial reactivity and the developmental stage of the brain. Depending on particular circumstances, the brain inflammatory response can promote neuroprotection, regeneration or neurodegeneration. Glial reactivity, regarded as the central phenomenon of brain inflammation, has also been used as an early marker of neurotoxicity. To study the mechanisms underlying the glial reactivity, serum-free aggregating brain cell cultures were used as an in vitro model to test the effects of conventional neurotoxicants such as organophosphate pesticides, heavy metals, excitotoxins and mycotoxins. This approach was found to be relevant and justified by the complex cell—cell interactions involved in the brain inflammatory response, the variability of the glial reactions and the multitude of mediators involved. All these variables need to be considered for the elucidation of the specific cellular and molecular reactions and their consequences caused by a given chemical insult. Human & Experimental Toxicology (2007) 26, 339—346

scholarly journals Identification of EBP50: A PDZ-containing Phosphoprotein that Associates with Members of the Ezrin-Radixin-Moesin Family

1997 ◽  
Vol 139 (1) ◽  
pp. 169-179 ◽  
Author(s):  
David Reczek ◽  
Mark Berryman ◽  
Anthony Bretscher
Keyword(s):  
Immunofluorescence Microscopy ◽  
Cultured Cells ◽  
Bovine Brain ◽  
Pdz Domains ◽  
Binding Partners ◽  
Phosphatase Treatment ◽  
Membrane Attachment ◽  
Polarized Epithelia ◽  
The Brain ◽  
Terminal Domains

Members of the ezrin-radixin-moesin (ERM) family of membrane–cytoskeletal linking proteins have NH2- and COOH-terminal domains that associate with the plasma membrane and the actin cytoskeleton, respectively. To search for ERM binding partners potentially involved in membrane association, tissue lysates were subjected to affinity chromatography on the immobilized NH2-terminal domains of ezrin and moesin, which comprise the ezrin-radixin-moesin–association domain (N-ERMAD). A collection of polypeptides at 50–53 kD from human placenta and at 58-59 kD from bovine brain bound directly to both N-ERMADs. The 50–53-kD placental proteins migrated as a major 50-kD species after phosphatase treatment, indicating that the heterogeneity is due to different phosphorylation states. We refer to these polypeptides as ERM-binding phosphoprotein 50 (EBP50). Sequence analysis of human EBP50 was used to identify an ∼2-kb human cDNA that encodes a 357-residue polypeptide. Recombinant EBP50 binds tightly to the N-ERMADs of ezrin and moesin. Peptide sequences from the brain candidate indicated that it is closely related to EBP50. EBP50 has two PSD-95/DlgA/ZO-1–like (PDZ) domains and is most likely a homologue of rabbit protein cofactor, which is involved in the protein kinase A regulation of the renal brush border Na+/H+ exchanger. EBP50 is widely distributed in tissues, and is particularly enriched in those containing polarized epithelia. Immunofluorescence microscopy of cultured cells and tissues revealed that EBP50 colocalizes with actin and ezrin in the apical microvilli of epithelial cells, and immunoelectron microscopy demonstrated that it is specifically associated with the microvilli of the placental syncytiotrophoblast. Moreover, EBP50 and ezrin can be coimmunoprecipitated as a complex from isolated human placental microvilli. These findings show that EBP50 is a physiologically relevant ezrin binding protein. Since PDZ domains are known to mediate associations with integral membrane proteins, one mode of membrane attachment of ezrin is likely to be mediated through EBP50.

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