scholarly journals Differentiated Paju cells have increased resistance to toxic effects of potassium ionophores.

2004 ◽  
Vol 51 (2) ◽  
pp. 539-544 ◽  
Author(s):  
Vera Teplova ◽  
Elina Jääskeläinen ◽  
Mirja Salkinoja-Salonen ◽  
Nils-Erik L Saris ◽  
Martina Serlachius ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane ◽  
Tumor Cell Line ◽  
Differentiated Cells ◽  
Apoptotic Protein ◽  
Undifferentiated Cells ◽  
Elevated Expression ◽  
The Impact ◽  
Microbial Toxins

In this study we have investigated the impact of differentiation of neuronal cells on their sensitivity to microbial toxins. We used the human neural crest-derived tumor cell line Paju, which can be induced to differentiation in vitro by treatment with phorbol 12-myristate 13-acetate. Addition of the highly toxic potassium ionophores cereulide (4.5 and 9.0 ng/ml) or valinomycin (20 ng/ml), to cultures of undifferentiated Paju cells caused collapse of the mitochondrial membrane potential - measured with the fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetrabenzimidazole carbocyanine iodide (JC-1) followed by detachment of the cells and their apoptotic death. After induced differentiation of the Paju cells, their mitochondria retained the membrane potential upon exposure to the toxins and the cells displayed increased resistance to apoptosis as compared with undifferentiated cells. This effect may be caused by an elevated expression of the anti-apoptotic protein Bcl-2 and of the neuroprotective factor, stanniocalcin, in differentiated cells.

scholarly journals Degradation of Mitochondria and Oxidative Stress as the Main Mechanism of Toxicity of Pristine Graphene on U87 Glioblastoma Cells and Tumors and HS-5 Cells

2019 ◽  
Vol 20 (3) ◽  
pp. 650 ◽  
Author(s):  
Sławomir Jaworski ◽  
Barbara Strojny ◽  
Ewa Sawosz ◽  
Mateusz Wierzbicki ◽  
Marta Grodzik ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Pristine Graphene ◽  
Infrared Measurements ◽  
The Impact

Due to the development of nanotechnologies, graphene and graphene-based nanomaterials have attracted immense scientific interest owing to their extraordinary properties. Graphene can be used in many fields, including biomedicine. To date, little is known about the impact graphene may have on human health in the case of intentional exposure. The present study was carried out on U87 glioma cells and non-cancer HS-5 cell lines as in vitro model and U87 tumors cultured on chicken embryo chorioallantoic membrane as in vivo model, on which the effects of pristine graphene platelets (GPs) were evaluated. The investigation consisted of structural analysis of GPs using transmission electron microscopy, Fourier transmission infrared measurements, zeta potential measurements, evaluation of cell morphology, assessment of cell viability, investigation of reactive oxygen species production, and investigation of mitochondrial membrane potential. The toxicity of U87 glioma tumors was evaluated by calculating the weight and volume of tumors and performing analyses of the ultrastructure, histology, and protein expression. The in vitro results indicate that GPs have dose-dependent cytotoxicity via ROS overproduction and depletion of the mitochondrial membrane potential. The mass and volume of tumors were reduced in vivo after injection of GPs. Additionally, the level of apoptotic and necrotic markers increased in GPs-treated tumors.

scholarly journals Effects of the Czech Propolis on Sperm Mitochondrial Function

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Miroslava Cedikova ◽  
Michaela Miklikova ◽  
Lenka Stachova ◽  
Martina Grundmanova ◽  
Zdenek Tuma ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Sperm Motility ◽  
Mitochondrial Membrane ◽  
Human Sperm ◽  
World Health ◽  
Mitochondrial Activity ◽  
The Impact ◽  
Mitochondrial Respiratory

Propolis is a natural product that honeybees collect from various plants. It is known for its beneficial pharmacological effects. The aim of our study was to evaluate the impact of propolis on human sperm motility, mitochondrial respiratory activity, and membrane potential. Semen samples from 10 normozoospermic donors were processed according to the World Health Organization criteria. Propolis effects on the sperm motility and mitochondrial activity parameters were tested in the fresh ejaculate and purified spermatozoa. Propolis preserved progressive motility of spermatozoa in the native semen samples. Oxygen consumption determined in purified permeabilized spermatozoa by high-resolution respirometry in the presence of adenosine diphosphate and substrates of complex I and complex II (stateOXPHOSI+II) was significantly increased in the propolis-treated samples. Propolis also increased uncoupled respiration in the presence of rotenone (stateETSII) and complex IV activity, but it did not influence state LEAK induced by oligomycin. Mitochondrial membrane potential was not affected by propolis. This study demonstrates that propolis maintains sperm motility in the native ejaculates and increases activities of mitochondrial respiratory complexes II and IV without affecting mitochondrial membrane potential. The data suggest that propolis improves the total mitochondrial respiratory efficiency in the human spermatozoa in vitro thereby having potential to improve sperm motility.

Protective Effect of SCUBE1 on Oxidative Stress-induced Apoptosis in Human Ovarian Granulosa Cells

2021 ◽  
Author(s):  
Huijiao Fu ◽  
Xuzi Cai ◽  
Qiwen Liu ◽  
Wei Yang ◽  
Xuefeng Wang
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Granulosa Cells ◽  
Mitochondrial Membrane ◽  
Ovarian Granulosa Cells ◽  
Multiple Organs ◽  
Cub Domain ◽  
Induced Apoptosis ◽  
The Impact

Abstract Background: Apoptosis of ovarian granulosa cells (GCs) is a sign of follicular atresia. This study aimed to explore the role and mechanism of signal peptide, CUB domain, epidermal growth factor-like protein1 (SCUBE1) in protecting GCs from apoptosis induced by hydrogen peroxide (H2O2). Results: SCUBE1 was expressed in women of all ages and had the highest expression level in the ovaries in multiple organs and tissues of KM mouse. In vitro cell experiments show that SCUBE1 pretreatment reduced H2O2-induced apoptosis and improved cell viability. SCUBE1 also blocked the production of ROS in cells and improved mitochondrial membrane potential. After SCUBE1 pretreatment, anti-apoptotic protein Bcl-2 expression was upregulated, whereas the expression of the pro-apoptotic proteins Bax, Bax/Bcl-2, Caspase-3, and p53 were downregulated. Analysis of the impact of SCUBE1 (c.1169C >G, p.P390R) mutation from the aspect of mutation pathogenicity; protein stability; and gene haplotype insufficiency, indicated that the p.P390R mutation is significantly pathogenic.Conclusions: This is the first time that the potential role of SCUBE1 in protecting GCs from H2O2-induced damage by blocking the production of ROS, increasing the mitochondrial membrane potential and regulating apoptosis-related proteins, attributing to POI, is studied. SCUBE1 (c.1169C >G, p.P390R) mutation has significant pathogenicity but the specific harm needs to be confirmed by further studies.

scholarly journals PC12 and THP-1 Cell Lines as Neuronal and Microglia Model in Neurobiological Research

2021 ◽  
Vol 11 (9) ◽  
pp. 3729
Author(s):  
Katarzyna Balon ◽  
Benita Wiatrak
Keyword(s):  
Cell Culture ◽  
Dna Damage ◽  
Cell Lines ◽  
Inflammatory Factor ◽  
Research Model ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Primary Cell Lines ◽  
Neurobiological Research ◽  
The Impact

Models based on cell cultures have become a useful tool in modern scientific research. Since primary cell lines are difficult to obtain and handle, neoplasm-derived lines like PC12 and THP-1 offer a cheap and flexible solution for neurobiological studies but require prior differentiation to serve as a neuronal or microglia model. PC12 cells constitute a suitable research model only after differentiation by incubation with nerve growth factor (NGF) and THP-1 cells after administering a differentiation factor such as phorbol 12-myristate-13-acetate (PMA). Still, quite often, studies are performed on these cancer cells without differentiation. The study aimed to assess the impact of PC12 or THP-1 cell differentiation on sensitivity to harmful factors such as Aβ25-35 (0.001–5 µM) (considered as one of the major detrimental factors in the pathophysiology of Alzheimer’s disease) or lipopolysaccharide (1–100 µM) (LPS; a pro-inflammatory factor of bacterial origin). Results showed that in most of the tests performed, the response of PC12 and THP-1 cells induced to differentiation varied significantly from the effect in undifferentiated cells. In general, differentiated cells showed greater sensitivity to harmful factors in terms of metabolic activity and DNA damage, while in the case of the free radicals, the results were heterogeneous. Obtained data emphasize the importance of proper differentiation of cell lines of neoplastic origin in neurobiological research and standardization of cell culture handling protocols to ensure reliable results.

scholarly journals Leishmanicidal Activity of Betulin Derivatives in Leishmania amazonensis; Effect on Plasma and Mitochondrial Membrane Potential, and Macrophage Nitric Oxide and Superoxide Production

2021 ◽  
Vol 9 (2) ◽  
pp. 320
Author(s):  
Wilmer Alcazar ◽  
Sami Alakurtti ◽  
Maritza Padrón-Nieves ◽  
Maija Liisa Tuononen ◽  
Noris Rodríguez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Leishmania Amazonensis ◽  
Superoxide Production ◽  
In Vitro Susceptibility ◽  
Intracellular Parasites ◽  
Betulin Derivatives

Herein, we evaluated in vitro the anti-leishmanial activity of betulin derivatives in Venezuelan isolates of Leishmania amazonensis, isolated from patients with therapeutic failure. Methods: We analyzed promastigote in vitro susceptibility as well as the cytotoxicity and selectivity of the evaluated compounds. Additionally, the activity of selected compounds was determined in intracellular amastigotes. Finally, to gain hints on their potential mechanism of action, the effect of the most promising compounds on plasma and mitochondrial membrane potential, and nitric oxide and superoxide production by infected macrophages was determined. Results: From the tested 28 compounds, those numbered 18 and 22 were chosen for additional studies. Both 18 and 22 were active (GI50 ≤ 2 µM, cytotoxic CC50 > 45 µM, SI > 20) for the reference strain LTB0016 and for patient isolates. The results suggest that 18 significantly depolarized the plasma membrane potential (p < 0.05) and the mitochondrial membrane potential (p < 0.05) when compared to untreated cells. Although neither 18 nor 22 induced nitric oxide production in infected macrophages, 18 induced superoxide production in infected macrophages. Conclusion: Our results suggest that due to their efficacy and selectivity against intracellular parasites and the potential mechanisms underlying their leishmanicidal effect, the compounds 18 and 22 could be used as tools for designing new chemotherapies against leishmaniasis.

scholarly journals Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential

2021 ◽  
Vol 7 (2) ◽  
pp. 130
Author(s):  
Nathan P. Wiederhold
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Candida Species ◽  
Mammalian Cells ◽  
Mitochondrial Membrane ◽  
Fungal Infections ◽  
Published Data ◽  
Candida Auris

Invasive infections caused by Candida that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non-albicans Candida species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by Candida auris, as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against Candida species, including C. albicans, C. glabrata, and C. auris strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.

scholarly journals Preferential and persistent impact of acute HIV-1 infection on CD4+ iNKT cells in colonic mucosa

2021 ◽  
Vol 118 (46) ◽  
pp. e2104721118
Author(s):  
Dominic Paquin-Proulx ◽  
Kerri G. Lal ◽  
Yuwadee Phuang-Ngern ◽  
Matthew Creegan ◽  
Andrey Tokarev ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Colonic Mucosa ◽  
Inkt Cells ◽  
Elevated Expression ◽  
Acute Hiv ◽  
The Impact ◽  
Hiv 1

Acute HIV-1 infection (AHI) results in the widespread depletion of CD4+ T cells in peripheral blood and gut mucosal tissue. However, the impact on the predominantly CD4+ immunoregulatory invariant natural killer T (iNKT) cells during AHI remains unknown. Here, iNKT cells from peripheral blood and colonic mucosa were investigated during treated and untreated AHI. iNKT cells in blood were activated and rapidly depleted in untreated AHI. At the time of peak HIV-1 viral load, these cells showed the elevated expression of cell death–associated transcripts compared to preinfection. Residual peripheral iNKT cells suffered a diminished responsiveness to in vitro stimulation early into chronic infection. Additionally, HIV-1 DNA, as well as spliced and unspliced viral RNA, were detected in iNKT cells isolated from blood, indicating the active infection of these cells in vivo. The loss of iNKT cells occurred from Fiebig stage III in the colonic mucosa, and these cells were not restored to normal levels after initiation of ART during AHI. CD4+ iNKT cells were depleted faster and more profoundly than conventional CD4+ T cells, and the preferential infection of CD4+ iNKT cells over conventional CD4+ T cells was confirmed by in vitro infection experiments. In vitro data also provided evidence of latent infection in iNKT cells. Strikingly, preinfection levels of peripheral blood CD4+ iNKT cells correlated directly with the peak HIV-1 load. These findings support a model in which iNKT cells are early targets for HIV-1 infection, driving their rapid loss from circulation and colonic mucosa.

Depolarized Mitochondrial Membrane Potential and Protection with Duroquinone in Isolated Perfused Lungs from Rats Exposed to Hyperoxia

2021 ◽  
Author(s):  
Said H. Audi ◽  
Swetha Ganesh ◽  
Pardis Taheri ◽  
Xiao Zhang ◽  
Ranjan K. Dash ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Complex I ◽  
Mitochondrial Membrane ◽  
Rhodamine 6G ◽  
Computational Approach ◽  
Experimental Protocol ◽  
Perfusion System ◽  
The Impact ◽  
Mitochondrial Uncoupler

Dissipation of mitochondrial membrane potential (Δψm) is a hallmark of mitochondrial dysfunction. our objective was to use a previously developed experimental-computational approach to estimate tissue Δψm in intact lungs of rats exposed to hyperoxia, and to evaluate the ability of duroquinone (DQ) to reverse any hyperoxia-induced depolarization of lung Δψm. Rats were exposed to hyperoxia (>95% O2) or normoxia (room air) for 48 hrs, after which lungs were excised and connected to a ventilation-perfusion system. The experimental protocol consisted of measuring the concentration of the fluorescent dye rhodamine 6G (R6G) during three single-pass phases: loading, washing, and uncoupling, in which the lungs were perfused with and without R6G, and with the mitochondrial uncoupler FCCP, respectively. For normoxic lungs, the protocol was repeated with 1) rotenone (complex I inhibitor), 2) rotenone and either DQ or its vehicle (DMSO), and 3) rotenone, glutathione (GSH), and either DQ or DMSO added to the perfusate. Hyperoxic lungs were studied with and without DQ and GSH added to the perfusate. Computational modeling was used to estimate lung Δψm from R6G data. Rat exposure to hyperoxia resulted in partial depolarization (-33 mV) of lung Δψm, and complex I inhibition depolarized lung Δψm by -83 mV. Results also demonstrate the efficacy of DQ to fully reverse both rotenone-induced and hyperoxia-induced lung Δψm depolarization. This study demonstrates hyperoxia-induced Δψm depolarization in intact lungs, and the utility of this approach for assessing the impact of potential therapies such as exogenous quinones that target mitochondria in intact lungs.

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