Taurine Exerts Robust Protection Against Hypoxia and Oxygen/Glucose Deprivation in Human Neuroblastoma Cell Culture

AbstractThere are many parameters in extrusion-based three-dimensional (3D) bioprinting of different materials that require fine-tuning to obtain the optimal print resolution and cell viability. To standardize this process, methods such as parameter optimization index (POI) have been introduced. The POI aims at pinpointing the optimal printing speed and pressure to achieve the highest accuracy keeping theoretical shear stress low. Here we applied the POI to optimize the process of 3D bioprinting human neuroblastoma cell-laden 2% sodium alginate (SA) hydrogel using freeform reversible embedding of suspended hydrogels (FRESH). Our results demonstrate a notable difference between optimal parameters for printing 2% SA with and without cells in the hydrogel. We also detected a significant influence of long-term cell culture on the printed constructs. This observation suggests that the POI has to be evaluated in the perspective of the final application. When taking these conditions into consideration, we could define a set of parameters that resulted in good quality prints maintaining high neuroblastoma cell viability (83% viable cells) during 7 days of cell culture using 2% SA and FRESH bioprinting. These results can be further used to manufacture neuroblastoma in vitro 3D culture systems to be used for cancer research.

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A novel quantitative high-throughput screen identifies drugs that both activate SUMO conjugation via the inhibition of microRNAs 182 and 183 and facilitate neuroprotection in a model of oxygen and glucose deprivation

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15609939 ◽

2015 ◽

Vol 36 (2) ◽

pp. 426-441 ◽

Cited By ~ 22

Author(s):

Joshua D Bernstock ◽

Yang-ja Lee ◽

Luca Peruzzotti-Jametti ◽

Noel Southall ◽

Kory R Johnson ◽

...

Keyword(s):

Small Molecules ◽

High Throughput ◽

Cortical Neurons ◽

High Throughput Screening ◽

Neuroblastoma Cell ◽

Glucose Deprivation ◽

Renilla Luciferase ◽

Luciferase Reporter ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma

The conjugation/de-conjugation of Small Ubiquitin-like Modifier (SUMO) has been shown to be associated with a diverse set of physiologic/pathologic conditions. The clinical significance and ostensible therapeutic utility offered via the selective control of the global SUMOylation process has become readily apparent in ischemic pathophysiology. Herein, we describe the development of a novel quantitative high-throughput screening (qHTS) system designed to identify small molecules capable of increasing SUMOylation via the regulation/inhibition of members of the microRNA (miRNA)-182 family. This assay employs a SHSY5Y human neuroblastoma cell line stably transfected with a dual firefly-Renilla luciferase reporter system for identification of specific inhibitors of either miR-182 or miR-183. In this study, we have identified small molecules capable of inducing increased global conjugation of SUMO in both SHSY5Y cells and rat E18-derived primary cortical neurons. The protective effects of a number of the identified compounds were confirmed via an in vitro ischemic model (oxygen/glucose deprivation). Of note, this assay can be easily repurposed to allow high-throughput analyses of the potential drugability of other relevant miRNA(s) in ischemic pathobiology.

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In Vitro Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons

Stem Cells International ◽

10.1155/2020/8841026 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Miia Juntunen ◽

Sanna Hagman ◽

Anaick Moisan ◽

Susanna Narkilahti ◽

Susanna Miettinen

Keyword(s):

Stem Cells ◽

Human Cell ◽

Glucose Deprivation ◽

Cell Types ◽

Oxygen Glucose Deprivation ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Stroke Models ◽

Induced Pluripotent

Stroke is a devastating neurological disorder and one of the leading causes of mortality and disability. To understand the cellular and molecular mechanisms of stroke and to develop novel therapeutic approaches, two different in vitro human cell-based stroke models were established using oxygen-glucose deprivation (OGD) conditions. In addition, the effect of adipose stem cells (ASCs) on OGD-induced injury was studied. In the present study, SH-SY5Y human neuroblastoma cells and human induced pluripotent stem cells (hiPSCs) were differentiated into neurons, cultured under OGD conditions (1% O2) for 24 h, and subjected to a reperfusion period for 24 or 72 h. After OGD, ASCs were cocultured with neurons on inserts for 24 or 72 h to study the neuroprotective potential of ASCs. The effect of OGD and ASC coculture on the viability, apoptosis, and proliferation of and axonal damage to neuronal cells was studied. The results showed that OGD conditions induced cytotoxicity and apoptosis of SH-SY5Y- and hiPSC-derived neurons, although more severe damage was detected in SH-SY5Y-derived neurons than in hiPSC-derived neurons. Coculture with ASCs was protective for neurons, as the number of dead ASC-cocultured neurons was lower than that of control cells, and coculture increased the proliferation of both cell types. To conclude, we developed in vitro human cell-based stroke models in SH-SY5Y- and hiPSC-derived neurons. This was the first time hiPSCs were used to model stroke in vitro. Since OGD had different effects on the studied cell types, this study highlights the importance of using several cell types in in vitro studies to confirm the outcomes of the study. Here, ASCs exerted a neuroprotective effect by increasing the proliferation and decreasing the death of SH-SY5Y- and hiPSC-derived neurons after OGD.

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Inhibition of T-type Ca2+ channel induces human neuroblastoma cell death and enhances neurotoxicity of bupivacaine

10.26226/morressier.58f5b031d462b80296c9d36c ◽

2017 ◽

Author(s):

Kumiko Tanaka

Keyword(s):

Cell Death ◽

Neuroblastoma Cell ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma

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p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181128112249 ◽

2020 ◽

Vol 17 (2) ◽

pp. 169-183 ◽

Cited By ~ 1

Author(s):

İrem Bozbey ◽

Suat Sari ◽

Emine Şalva ◽

Didem Kart ◽

Arzu Karakurt

Keyword(s):

Molecular Modeling ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Cytotoxic Agents ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Modeling Studies ◽

Broth Microdilution Method ◽

Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

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