Utilizing Biomarker Techniques: Cellular Membrane Potential as a Biomarker of Subchronic Toxicity

2009 ◽  
pp. 177-177-11
Author(s):  
DJ Fort ◽  
EL Stover ◽  
SL Burks ◽  
RA Atherton ◽  
JT Blankemeyer
Keyword(s):  
Membrane Potential ◽  
Cellular Membrane ◽  
Subchronic Toxicity

Investigation of the effect of magnetite iron oxide particles size on cytotoxicity in A549 cell line

2019 ◽  
Vol 35 (11-12) ◽  
pp. 703-713 ◽  
Author(s):  
Athena Rafieepour ◽  
Mansour R Azari ◽  
Habibollah Peirovi ◽  
Fariba Khodagholi ◽  
Jalal Pourahmad Jaktaji ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Iron Oxide ◽  
Cell Line ◽  
Cellular Membrane ◽  
Human Cell Line ◽  
Control Measures ◽  
Iron Oxide Particles ◽  
Magnetite Particles ◽  
Oxide Particles ◽  
Reduced Rate

Introduction: Magnetite as iron oxide is widely used in various industries, in the pharmaceutical industry in particular where it is used for its magnetic properties. The environmental and occupational exposure to airborne nanoparticles and microparticles of iron oxide compounds have been reported. Since authors have reported contradictory results, the objective of this study was to investigate the effect of particles’ size in their toxicities. Methods: The human cell line A549 was exposed with magnetite iron oxide in two size categories of micro (≥5 µm) and nano (<100 nm), with four concentrations of 10, 50, 100, and 250 µg/ml at two time periods of 24 and 72 h. The cell viability, reactive oxygen species (ROS), changes in mitochondrial membrane potential, and incidence of apoptosis were studied. Results: Nano and micro magnetite particles demonstrated diverse toxicity effects on the A549 cell line at the 24- and 72-h exposure periods; however, the effects produced were time- and concentration-dependent. Nano magnetite particles produced greater cellular toxicities in forms of decreased viabilities at concentration exposures greater than 50 µg/ml ( p < 0.05), along with increased ROS ( p < 0.05), decreased cellular membrane potential ( p < 0.05), and reduced rate of apoptosis ( p < 0.05). Discussion: The results of this study demonstrated that magnetite iron in nano-range sizes had a greater absorbability for the A549 cell line compared to micro sizes, and at the same time, nanoparticles were more toxic than microparticles, demonstrating higher production of ROS and decreased viabilities. Considering the greater toxicity of nanoparticles of magnetite iron in this study, thorough precautionary control measures must be taken before they can be used in various industries.

scholarly journals Tissue-specific modification of cellular bioelectrical activities using the chemogenetic tool, DREADD, in zebrafish

2021 ◽  
Author(s):  
Martin R. Silic ◽  
GuangJun Zhang
Keyword(s):  
Membrane Potential ◽  
Model Organism ◽  
Cellular Membrane ◽  
Designer Drugs ◽  
Pigment Cells ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Tissue Specific ◽  
Morphological Alterations ◽  
Research Fields

Cellular electronic activity plays an essential role in neuronal communication. Manipulation and visualization of cellular membrane potential remain essential tasks in order to study electrical signaling in living organisms. Light-controlled optogenetic and designed chemical-controlled chemogenetic tools were developed to manipulate cellular electric activities for neuroscience research. One of the most common chemogenetic tools is DREADD (designer receptors exclusively activated by designer drugs). It has been extensively utilized due to its convenience and long-lasting effects in murine and primate models, but not in zebrafish, a leading model organism in various research fields. Here, we first establish multiple tissue-specific transgenic zebrafish lines that express two different DREADDs with a genetically encoded voltage indicator, ASAP2s. We observed voltage changes in zebrafish melanophores, epidermis, and neurons by hM4DGi or rM3DGs receptors measured by ASAP2s fluorescence intensity. Alteration to melanophore bioelectricity by DREADD generated dynamic electric signals and resulted in morphological alterations to pigment cells. We also tested a few agonists and found that the latest generation performs better than clozapine N-oxide (CNO). Collectively, our experiments demonstrate that DREADD can be utilized to manipulate cell-specific membrane potential in the zebrafish model. The availability of this tool in zebrafish will offer a new resource for a variety of bioelectricity research fields such as neuroscience, cardiology, and developmental biology.

scholarly journals Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cellular Membrane Potential Are Predictors of E-Liquid Induced Cellular Toxicity

2020 ◽  
Vol 22 (Supplement_1) ◽  
pp. S4-S13
Author(s):  
Eva Correia-Álvarez ◽  
James E Keating ◽  
Gary Glish ◽  
Robert Tarran ◽  
M Flori Sassano
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cellular Membrane ◽  
Liquid Composition ◽  
Oxygen Species ◽  
Policy Makers ◽  
Cellular Toxicity ◽  
The U.S

Abstract Introduction The use of flavors in electronic cigarettes appeals to adults and never-smoking youth. Consumption has rapidly increased over the last decade, and in the U.S. market alone, there are over 8000 unique flavors. The U.S. Food and Drug Administration (FDA) has begun to regulate e-liquids, but many have not been tested, and their impact, both at the cellular level, and on human health remains unclear. Methods We tested e-liquids on the human cell line HEK293T and measured toxicity, mitochondrial membrane potential (ΔΨ  m), reactive oxygen species production (ROS), and cellular membrane potential (Vm) using high-throughput screening (HTS) approaches. Our HTS efforts included single-dose and 16-point dose–response curves, which allowed testing of ≥90 commercially available e-liquids in parallel to provide a rapid assessment of cellular effects as a proof of concept for a fast, preliminary toxicity method. We also investigated the chemical composition of the flavors via gas chromatography–mass spectrometry. Results We found that e-liquids caused a decrease in ΔΨ  m and Vm and an increase in ROS production and toxicity in a dose-dependent fashion. In addition, the presence of five specific chemical components: vanillin, benzyl alcohol, acetoin, cinnamaldehyde, and methyl-cyclopentenolone, but not nicotine, were linked with the changes observed in the cellular traits studied. Conclusion Our data suggest that ΔΨ  m, ROS, Vm, and toxicity may be indicative of the extent of cell death upon e-liquid exposure. Further research on the effect of flavors should be prioritized to help policy makers such as the FDA to regulate e-liquid composition. Implications E-liquid cellular toxicity can be predicted using parameters amenable to HTS. Our data suggest that ΔΨ  m, ROS, Vm, and toxicity may be indicative of the extent of cell death upon e-liquid exposure, and this toxicity is linked to the chemical composition, that is, flavoring components. Further research on the effect of flavors should be prioritized to help policy makers such as the FDA to regulate e-liquid composition.

A model for understanding membrane potential using springs

2005 ◽  
Vol 29 (4) ◽  
pp. 204-207 ◽  
Author(s):  
David L. Cardozo
Keyword(s):  
Membrane Potential ◽  
Simple Model ◽  
Cellular Membrane ◽  
Equilibrium Potential ◽  
Ionic Conductance ◽  
Similar Form ◽  
Ionic Equilibrium ◽  
Ionic Conductances ◽  
The Relationship

In this report, I present a simple model using springs to conceptualize the relationship between ionic conductances across a cellular membrane and their effect on membrane potential. The equation describing the relationships linking membrane potential, ionic equilibrium potential, and ionic conductance is of similar form to that describing the force generated by a spring as a function of its displacement. The spring analogy is especially useful in helping students to conceptualize the effects of multiple conductances on membrane potential.

scholarly journals Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
David A. C. Messerer ◽  
Stephanie Denk ◽  
Karl J. Föhr ◽  
Rebecca Halbgebauer ◽  
Christian K. Braun ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Hemorrhagic Shock ◽  
Cellular Membrane ◽  
Significant Shift ◽  
Strong Response ◽  
Electrophysiological Response ◽  
Polymorphonuclear Granulocytes ◽  
Complement C5a ◽  
Induced Changes

Background. Polymorphonuclear granulocytes (PMN) play a crucial role in host defense. Physiologically, exposure of PMN to the complement activation product C5a results in a protective response against pathogens, whereas in the case of systemic inflammation, excessive C5a substantially impairs neutrophil functions. To further elucidate the inability of PMN to properly respond to C5a, this study investigates the role of the cellular membrane potential of PMN in response to C5a. Methods. Electrophysiological changes in cellular and mitochondrial membrane potential and intracellular pH of PMN from human healthy volunteers were determined by flow cytometry after exposure to C5a. Furthermore, PMN from male Bretoncelles-Meishan-Willebrand cross-bred pigs before and three hours after severe hemorrhagic shock were analyzed for their electrophysiological response. Results. PMN showed a significant dose- and time-dependent depolarization in response to C5a with a strong response after one minute. The chemotactic peptide fMLP also evoked a significant shift in the membrane potential of PMN. Acidification of the cellular microenvironment significantly enhanced depolarization of PMN. In a clinically relevant model of porcine hemorrhagic shock, the C5a-induced changes in membrane potential of PMN were markedly diminished compared to healthy littermates. Overall, these membrane potential changes may contribute to PMN dysfunction in an inflammatory environment.

The adsorption behaviour of carbon nanodots modulated by cellular membrane potential

2020 ◽  
Vol 7 (3) ◽  
pp. 880-890 ◽  
Author(s):  
Shuyuan Zhang ◽  
Changqing Xiao ◽  
Hang He ◽  
Ziqiang Xu ◽  
Beibei Wang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cellular Membrane ◽  
Adsorption Behavior ◽  
Carbon Nanodots ◽  
Adsorption Behaviour ◽  
Cellular Membranes

A schematic comparison of the adsorption behavior of CDs on liposomes and cellular membranes.

Grape-seed procyanidins modulate cellular membrane potential and nutrient-induced GLP-1 secretion in STC-1 cells

2014 ◽  
Vol 306 (5) ◽  
pp. C485-C492 ◽  
Author(s):  
Noemi González-Abuín ◽  
Neus Martínez-Micaelo ◽  
Mayte Blay ◽  
Brian D. Green ◽  
Montserrat Pinent ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Hormone Secretion ◽  
Cellular Membrane ◽  
Grape Seed ◽  
Plasma Membrane Potential ◽  
Low Concentrations ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
High Concentrations

Grape-seed procyanidin extracts (GSPE) modulate glucose homeostasis, and it was suggested that GSPE may achieve this by enhancing the secretion of incretin hormones such as glucagon-like peptide-1 (GLP-1). Therefore, the aim of the present study is to examine in detail the effects of GSPE on intestinal endocrine cells (STC-1). GSPE was found to modulate plasma membrane potential in enteroendocrine cells, inducing depolarization at low concentrations (0.05 mg/l) and hyperpolarization at high concentrations (50 mg/l), and surprisingly this was also accompanied by suppressed GLP-1 secretion. Furthermore, how GSPE affects STC-1 cells under nutrient-stimulated conditions (i.e., glucose, linoleic acid, and l-proline) was also explored, and we found that the higher GSPE concentration was effective in limiting membrane depolarization and reducing GLP-1 secretion. Next, it was also examined whether GSPE affected mitochondrial membrane potential, and it was found that this too is altered by GSPE; however, this does not appear to explain the observed effects on plasma membrane potential and GLP-1 secretion. In conclusion, our results show that grape-seed procyanidins modulate cellular membrane potential and nutrient-induced enteroendocrine hormone secretion in STC-1 cells.

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