scholarly journals Adenosine Depletion as A New Strategy to Decrease Glioblastoma Stem-Like Cells Aggressiveness

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1353 ◽  
Author(s):  
Ignacio Niechi ◽  
Atenea Uribe-Ojeda ◽  
José Ignacio Erices ◽  
Ángelo Torres ◽  
Daniel Uribe ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Cell Subpopulation ◽  
Migration And Invasion ◽  
Transwell Assay ◽  
Extracellular Adenosine ◽  
Hypoxic Conditions ◽  
New Strategy ◽  
Dependent Cell ◽  
A Cell ◽  
The Brain

Glioblastoma is the brain tumor with the worst prognosis. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine, which are increased even more under hypoxic conditions. Under hypoxia, adenosine signaling is related to HIF-2α expression, enhancing cell aggressiveness. Adenosine can be degraded using recombinant adenosine deaminase (ADA) to revert its pathological effects. The aim of this study was to degrade adenosine using ADA in order to decrease malignancy of GSCs. Adenosine depletion was performed using recombinant ADA. Migration and invasion were measured by transwell and matrigel-coated transwell assay, respectively. HIF-2α-dependent cell migration/invasion decreased in GSCs treated with ADA under hypoxia. MRPs-mediated chemoresistance and colony formation decreased in treatment with ADA. In conclusion, adenosine depletion using adenosine deaminase decreases GSCs aggressiveness.

scholarly journals Decreased Equilibrative Nucleoside Transporter 1 (ENT1) Activity Contributes to the High Extracellular Adenosine Levels in Mesenchymal Glioblastoma Stem-Like Cells

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1914 ◽  
Author(s):  
Sebastián Alarcón ◽  
María de los Ángeles Toro ◽  
Carolina Villarreal ◽  
Rómulo Melo ◽  
Rodrigo Fernández ◽  
...  
Keyword(s):  
Adenosine Monophosphate ◽  
Prostatic Acid Phosphatase ◽  
Cell Subpopulation ◽  
Migration And Invasion ◽  
Nucleoside Transporter ◽  
Extracellular Adenosine ◽  
Adenosine Uptake ◽  
A Cell ◽  
High Level ◽  
Lower Expression

Glioblastoma multiforme is one of the most malignant types of cancer. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine which has been associated with increased chemoresistance, migration, and invasion in glioblastoma. In this study, we attempted to elucidate the mechanisms that control extracellular adenosine levels in GSC subtypes. By using primary and U87MG-derived GSCs, we associated increased extracellular adenosine with the mesenchymal phenotype. [3H]-adenosine uptake occurred mainly through the equilibrative nucleoside transporters (ENTs) in GSCs, but mesenchymal GSCs have lower expression and ENT1-mediated uptake activity than proneural GSCs. By analyzing expression and enzymatic activity, we determined that ecto-5′-nucleotidase (CD73) is predominantly expressed in proneural GSCs, driving AMPase activity. While in mesenchymal GSCs, both CD73 and Prostatic Acid Phosphatase (PAP) contribute to the AMP (adenosine monophosphate) hydrolysis. We did not observe significant differences between the expression of proteins involved in the metabolization of adenosine among the GCSs subtypes. In conclusion, the lower expression and activity of the ENT1 transporter in mesenchymal GSCs contributes to the high level of extracellular adenosine that these GSCs present.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

2020 ◽  
Vol 16 (1) ◽  
pp. 90-93
Author(s):  
Carmen E. Iriarte ◽  
Ian G. Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Candida Glabrata ◽  
High Sensitivity ◽  
Time Dependent ◽  
Colony Forming Units ◽  
Dependent Cell ◽  
The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

Panax Notoginseng Saponins Promote Cell Death and Chemosensitivity in Pancreatic Cancer through the Apoptosis and Autophagy Pathways

2020 ◽  
Vol 20 ◽  
Author(s):  
Li-Chao Yao ◽  
Lun Wu ◽  
Wei Wang ◽  
Lu-Lu Zhai ◽  
Lin Ye ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Panax Notoginseng ◽  
Panax Notoginseng Saponins ◽  
Transwell Assay ◽  
Pancreatic Cancer Cells ◽  
New Strategy ◽  
Induced Apoptosis ◽  
Promote Cell Death

Background:: Panax Notoginseng Saponins (PNS) is used as traditional Chinese medicine for ischemic stroke and cardiovascular disease, it has been proven to possess anticancer activity recently. Objective:: In this study, we aimed to explore the anticancer curative effect and potential mechanisms of PNS in pancreatic cancer cells. Methods:: Pancreatic cancer Miapaca2 and PANC-1 cells were treated with PNS and Gemcitabine (Gem), respectively. Then the cell viability was assessed by CCK-8 assay, cell proliferation was tested by colony formation assay and EdU cell proliferation assay, cell migration and invasiveness were tested by wound healing assay and transwell assay respectively, and cell apoptosis was detected by flow cytometry. Finally, we detected the expression levels of proteins related to migration, apoptosis and autophagy through Western blotting. Results:: PNS not only inhibited the proliferation, migration, invasion and autophagy of Miapaca2 and PANC-1 cells, but also induced apoptosis and promoted chemosensitivity of pancreatic cancer cells to Gem. Conclusion:: PNS may exhibit cytotoxicity and increase chemosensitivity of pancreatic cancer cells to Gem by inhibiting autophagy and inducing apoptosis, providing a new strategy and potential treatment option for pancreatic cancer.

scholarly journals Development of a New Polymeric Nanocarrier Dedicated to Controlled Clozapine Delivery at the Dopamine D2-Serotonin 5-HT1A Heteromers

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1000
Author(s):  
Sylwia Łukasiewicz
Keyword(s):  
Physicochemical Parameters ◽  
Modern Science ◽  
Dopamine D2 ◽  
Targeted Transport ◽  
First Choice ◽  
New Strategy ◽  
Cell Components ◽  
Second Generation Antipsychotic ◽  
The Brain ◽  
Polymeric Nanocarrier

Clozapine, the second generation antipsychotic drug, is one of the prominent compounds used for treatment of schizophrenia. Unfortunately, use of this drug is still limited due to serious side effects connected to its unspecific and non-selective action. Nevertheless, clozapine still remains the first-choice drug for the situation of drug-resistance schizophrenia. Development of the new strategy of clozapine delivery into well-defined parts of the brain has been a great challenge for modern science. In the present paper we focus on the presentation of a new nanocarrier for clozapine and its use for targeted transport, enabling its interaction with the dopamine D2 and serotonin 5-HT1A heteromers (D2-5-HT1A) in the brain tissue. Clozapine polymeric nanocapsules (CLO-NCs) were prepared using anionic surfactant AOT (sodium docusate) as an emulsifier, and bio-compatible polyelectrolytes such as: poly-L-glutamic acid (PGA) and poly-L-lysine (PLL). Outer layer of the carrier was grafted by polyethylene glycol (PEG). Several variants of nanocarriers containing the antipsychotic varying in physicochemical parameters were tested. This kind of approach may enable the availability and safety of the drug, improve the selectivity of its action, and finally increase effectiveness of schizophrenia therapy. Moreover, the purpose of the manuscript is to cover a wide scope of the issues, which should be considered while designing a novel means for drug delivery. It is important to determine the interactions of a new nanocarrier with many cell components on various cellular levels in order to be sure that the new nanocarrier will be safe and won’t cause undesired effects for a patient.

scholarly journals Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takahiro Morito ◽  
Ryuichi Harada ◽  
Ren Iwata ◽  
Yiqing Du ◽  
Nobuyuki Okamura ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Post Injection ◽  
Affibody Molecule ◽  
Positron Emission ◽  
A Cell ◽  
Protein Binders ◽  
Rapid Clearance ◽  
Labelling Method ◽  
The Brain ◽  
Ex Vivo Study

AbstractBrain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the performance of an engineered, blood–brain barrier (BBB)-permeable affibody molecule that exhibits rapid clearance from the brain, which was radiolabelled using a unique fluorine-18 labelling method, a cell-free protein radiosynthesis (CFPRS) system. AS69, a small (14 kDa) dimeric affibody molecule that binds to the monomeric and oligomeric states of α-synuclein, was newly designed for brain delivery with an apolipoprotein E (ApoE)-derived brain shuttle peptide as AS69-ApoE (22 kDa). The radiolabelled products 18F-AS69 and 18F-AS69-ApoE were successfully synthesised using the CFPRS system. Notably, 18F-AS69-ApoE showed higher BBB permeability than 18F-AS69 in an ex vivo study at 10 and 30 min post injection and was partially cleared from the brain at 120 min post injection. These results suggest that small, a brain shuttle peptide-fused fluorine-18 labelled protein binders can potentially be utilised for brain molecular imaging.

scholarly journals Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Computational Models ◽  
Neuronal Damage ◽  
Living Organism ◽  
The Body ◽  
Mitochondrial Functions ◽  
A Cell ◽  
The Brain ◽  
And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

Structural features and functional domains of amassin-1, a cell-binding olfactomedin protein

2007 ◽  
Vol 85 (5) ◽  
pp. 552-562 ◽  
Author(s):  
Brian J. Hillier ◽  
Victor D. Vacquier
Keyword(s):  
Disulfide Bonds ◽  
Biological Activities ◽  
Structural Features ◽  
Body Cavity ◽  
Binding Activity ◽  
Coiled Coils ◽  
Cell Binding ◽  
Calcium Dependent ◽  
Dependent Cell ◽  
A Cell

Amassin-1 mediates a rapid cell adhesion that tightly adheres sea urchin coelomocytes (body cavity immunocytes) together. Three major structural regions exist in amassin-1: a short β region, 3 coiled coils, and an olfactomedin domain. Amassin-1 contains 8 disulfide-bonded cysteines that, upon reduction, render it inactive. Truncated forms of recombinant amassin-1 were expressed and purified from Pichia pastoris and their disulfide bonding and biological activities investigated. Expressed alone, the olfactomedin domain contained 2 intramolecular disulfide bonds, existed in a monomeric state, and inhibited amassin-1-mediated clotting of coelomocytes by a calcium-dependent cell-binding activity. The N-terminal β region, containing 3 cysteines, was not required for clotting activity. The coiled coils may dimerize amassin-1 in a parallel orientation through a homodimerizing disulfide bond. Neither amassin-1 fragments that were disulfide-linked as dimers or that were engineered to exist as dimers induced coelomocytes clotting. Clotting required higher multimeric states of amassin-1, possibly tetramers, which occurred through the N-terminal β region and (or) the first segment of coiled coils.

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