Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

How does the cell overcome LCP nanoparticle-induced calcium toxicity?

ABSTRACT: To address the question of how cells respond to the possible Ca(2+) toxicity caused by the release of Ca(2+) into the cytoplasm by LCP nanoparticles, a series of in vitro and in vivo studies using Ca(2+) pump inhibitors were conducted. The results indicated that two major Ca(2+) pumps on the plasma membrane and the mitochondrial membrane, respectively, were able to rapidly respond to the elevated cytosolic Ca(2+) concentration and prevent Ca(2+)-induced apoptosis or necrosis. However, exposure to specific inhibitors of calcium pumps would cause LCP-treated H460 cells to undergo necrosis both in vitro and in vivo. These results demonstrated that the Ca(2+) delivered by LCP was not toxic to cells when the cells contain functional Ca(2+) pumps.

SUBMITTER: Tseng YC

PROVIDER: S-EPMC3946490 | biostudies-other | 2013 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

How does the cell overcome LCP nanoparticle-induced calcium toxicity?

Tseng Yu-Cheng YC Yang Angela A Huang Leaf L

Molecular pharmaceutics 20131001 11

To address the question of how cells respond to the possible Ca(2+) toxicity caused by the release of Ca(2+) into the cytoplasm by LCP nanoparticles, a series of in vitro and in vivo studies using Ca(2+) pump inhibitors were conducted. The results indicated that two major Ca(2+) pumps on the plasma membrane and the mitochondrial membrane, respectively, were able to rapidly respond to the elevated cytosolic Ca(2+) concentration and prevent Ca(2+)-induced apoptosis or necrosis. However, exposure t ...[more]

PMID: 24032396

Similar Datasets

Intracellular calcium levels as screening tool for nanoparticle toxicity.

Project description:The use of engineered nano-sized materials led to revolutionary developments in many industrial applications and in the medical field. These materials, however, also may cause cytotoxicity. In addition to size, surface properties and shape were identified as relevant parameters for cell damage. Cell damage may occur as disruption of membrane integrity, induction of apoptosis and by organelle damage. Generation of oxidative stress may serve as an indicator for cytotoxicity. Effects occurring upon short contact of particles with cells, for instance in the systemic blood circulation, could be identified according to increases of intracellular [Ca(2+) ] levels, which are caused by variety of toxic stimuli. Negatively charged, neutral and positively charged polystyrene particles of different sizes were used to study the role of size and surface properties on viability, membrane disruption, apoptosis, lysosome function, intracellular [Ca(2+) ] levels and generation of oxidative stress. Silica particles served to test this hypothesis. Twenty nm polystyrene particles as well as 12 nm and 40 nm silica particles caused membrane damage and apoptosis with no preference of the surface charge. Only 20 nm plain and amine functionalized polystyrene particles cause oxidative stress and only the plain particles lysosomal damage. A potential role of surface charge was identified for 200 nm polystyrene particles, where only the amidine particles caused lysosomal damage. Increases in intracellular [Ca(2+) ] levels and cytotoxicity after 24 h was often linked but determination of intracellular [Ca(2+) ] levels could serve to characterize further the type of membrane damage.

| S-EPMC4606983 | biostudies-literature

Kupffer Cell Isolation for Nanoparticle Toxicity Testing.

Project description:The large majority of in vitro nanotoxicological studies have used immortalized cell lines for their practicality. However, results from nanoparticle toxicity testing in immortalized cell lines or primary cells have shown discrepancies, highlighting the need to extend the use of primary cells for in vitro assays. This protocol describes the isolation of mouse liver macrophages, named Kupffer cells, and their use to study nanoparticle toxicity. Kupffer cells are the most abundant macrophage population in the body and constitute part of the reticulo-endothelial system (RES), responsible for the capture of circulating nanoparticles. The Kupffer cell isolation method reported here is based on a 2-step perfusion method followed by purification on density gradient. The method, based on collagenase digestion and density centrifugation, is adapted from the original protocol developed by Smedsrød et al. designed for rat liver cell isolation and provides high yield (up to 14 x 10(6) cells per mouse) and high purity (>95%) of Kupffer cells. This isolation method does not require sophisticated or expensive equipment and therefore represents an ideal compromise between complexity and cell yield. The use of heavier mice (35-45 g) improves the yield of the isolation method but also facilitates remarkably the procedure of portal vein cannulation. The toxicity of functionalized carbon nanotubes f-CNTs was measured in this model by the modified LDH assay. This method assesses cell viability by measuring the lack of structural integrity of Kupffer cell membrane after incubation with f-CNTs. Toxicity induced by f-CNTs can be measured consistently using this assay, highlighting that isolated Kupffer cells are useful for nanoparticle toxicity testing. The overall understanding of nanotoxicology could benefit from such models, making the nanoparticle selection for clinical translation more efficient.

| S-EPMC4692542 | biostudies-other

Genome-wide transcriptional analysis of silica nanoparticle-induced toxicity in zebrafish embryos.

Project description:Although silica nanoparticles (SiNPs) have a promising application in biomedical fields, there is still a lack of comprehensive understanding of genome-wide transcriptional analysis. This study aims to clarify the toxic effect and molecular mechanisms of SiNPs in zebrafish embryos based on microarray analysis and bioinformatics analysis. Microarray data analysis demonstrated that SiNP-induced toxicity in zebrafish embryos affected expression of 2515 genes, including 1107 genes that were up-regulated and 1408 genes that were down-regulated. These differentially expressed genes were subjected to bioinformatics analysis for exploring the biological processes triggered by SiNPs in zebrafish embryos. Gene ontology analysis showed that SiNPs caused significant changes in gene expression patterns related to many important functions, including response to stimuli, immune response, cellular processes, and embryonic development. In addition, pathway analysis and Signal-net analysis indicated that the gap junction, vascular smooth muscle contraction, and metabolic pathways, apoptosis, the MAPK signaling pathway, the calcium signaling pathway and the JAK-STAT signaling pathway were the most prominent significant pathways in SiNP-induced toxicity in zebrafish embryos. In addition, the results from qRT-PCR and western blot analysis showed that the IL-6 dependent JAK1/STAT3 signaling pathway was activated by SiNPs in zebrafish embryos. In summary, our data will provide compelling clues for further exploration of SiNP-induced toxicity in zebrafish embryos.

| S-EPMC6062350 | biostudies-literature

Far-Infrared Ameliorates Pb-Induced Renal Toxicity via Voltage-Gated Calcium Channel-Mediated Calcium Influx.

Project description:Far-infrared (FIR), characterized by its specific electromagnetic wavelengths, has emerged as an adjunctive therapeutic strategy for various diseases, particularly in ameliorating manifestations associated with renal disorders. Although FIR was confirmed to possess antioxidative and anti-inflammatory attributes, the intricate cellular mechanisms through which FIR mitigates lead (Pb)-induced nephrotoxicity remain enigmatic. In this study, we investigated the effects of FIR on Pb-induced renal damage using in vitro and in vivo approaches. NRK52E rat renal cells exposed to Pb were subsequently treated with ceramic-generated FIR within the 9~14 μm range. Inductively coupled plasma mass spectrometry (ICP-MS) enabled quantitative Pb concentration assessment, while proteomic profiling unraveled intricate cellular responses. In vivo investigations used Wistar rats chronically exposed to lead acetate (PbAc) at 6 g/L in their drinking water for 15 weeks, with or without a concurrent FIR intervention. Our findings showed that FIR upregulated the voltage-gated calcium channel, voltage-dependent L type, alpha 1D subunit (CaV1.3), and myristoylated alanine-rich C kinase substrate (MARCKS) (p < 0.05), resulting in increased calcium influx (p < 0.01), the promotion of mitochondrial activity, and heightened ATP production. Furthermore, the FIR intervention effectively suppressed ROS production, concurrently mitigating Pb-induced cellular death. Notably, rats subjected to FIR exhibited significantly reduced blood Pb levels (30 vs. 71 μg/mL; p < 0.01), attenuated Pb-induced glomerulosclerosis, and enhanced Pb excretion compared to the controls. Our findings suggest that FIR has the capacity to counteract Pb-induced nephrotoxicity by modulating calcium influx and optimizing mitochondrial function. Overall, our data support FIR as a novel therapeutic avenue for Pb toxicity in the kidneys.

| S-EPMC10649088 | biostudies-literature

Effect of Nanoparticle Surface Coating on Cell Toxicity and Mitochondria Uptake.

Project description:We report on the effect of surface charge and the ligand coating composition of CdSe/ZnS core/shell quantum dot (QD) nanoparticles on human keratinocyte toxicity using fluorescent microscopy, flow cytometry, transmission electron microscopy. Two commonly reported positive charged (cysteamine, polyethylenimine) and two negative charged (glutathione, dihydrolipoic acid) ligands were studied. The QDs were fully characterized by UV-vis absorption spectroscopy, fluorescence emission spectroscopy, dynamic light scattering and zeta potential. Differences in surface coatings and charges were evaluated against cellular uptake, ROS generation, cytotoxicity, and mitochondrial targeting. Results show that the negative charged QDs coated with GSH exhibit excellent water solubility, high quantum yield and low cytotoxicity. Ligand composition is more important in ROS generation than surface charge whereas surface charge is an important driver of cytotoxicity. Most importantly we observe the selective accumulation of glutathione coated QDs in vesicles in the mitochondria matrix. This observation suggests a new strategy for developing mitochondria-targeted nanomaterials for drug/gene delivery.

| S-EPMC6800125 | biostudies-literature

PASIV: A Pooled Approach-Based Workflow to Overcome Toxicity-Induced Design of Experiments Failures and Inefficiencies.

Project description:We present here a newly developed workflow─which we have called PASIV─designed to provide a solution to a practical problem with design of experiments (DoE) methodology: i.e., what can be done if the scoping phase of the DoE cycle is severely hampered by burden and toxicity issues (caused by either the metabolite or an intermediary), making it unreliable or impossible to proceed to the screening phase? PASIV─standing for pooled approach, screening, identification, and visualization─was designed so the (viable) region of interest can be made to appear through an interplay between biology and software. This was achieved by combining multiplex construction in a pooled approach (one-pot reaction) with a viability assay and with a range of bioinformatics tools (including a novel construct matching tool). PASIV was tested on the exemplar of the lycopene pathway─under stressful constitutive expression─yielding a region of interest with comparatively stronger producers.

| S-EPMC8938949 | biostudies-literature

The addition of mammalian cell culture medium impacts nanoparticle toxicity in zebrafish.

Project description:Engineered nanomaterials (ENMs) are ubiquitous in contemporary applications, yet their environmental and human health impacts remain inadequately understood. This study addresses the challenge of identifying potential risks associated with ENM exposure by highlighting the significant variability in existing research methodologies. Without a systematic collection of toxicological data that encompasses standardized materials, relevant platforms, and assays, the task of identifying potential risks linked to ENM exposure becomes an intricate challenge. In vitro assessments often use media rich in ionic species, such as RPMI and fetal bovine serum (FBS). Zebrafish embryos, known to develop normally in low-ionic environments, were exposed to Cerium Oxide, Zinc Oxide, and Graphene Oxides in different media at varying concentrations. Here, we discovered that zebrafish embryos tolerated a mix of 80 % RPMI, 2 % FBS, and 1 % antibiotic cocktail. The results revealed that adverse effects observed in zebrafish with certain nanomaterials in Ultra-Pure (UP) water were mitigated in cell culture medium, emphasizing the importance of revisiting previously considered non-toxic materials in vitro. The zebrafish results underscore the importance of utilizing a multidimensional in vivo platform to gauge the biological activity of nanomaterials accurately.

| S-EPMC11015449 | biostudies-literature

Alpha-Lipoic Acid Can Overcome The Reduced Developmental Competency Induced by Alcohol Toxicity during Ovine Oocyte Maturation.

Project description:ObjectiveAlpha-lipoic acid (ALA) as a strong antioxidant has a protective effect. This study was designed to assess whether supplementation of maturation medium with ALA during in vitro maturation (IVM) can attenuate the toxic effect of ethanol.Materials and methodsIn this experimental study, to assess the antioxidant capacity of ALA challenged by 1% ethanol during in vitro maturation, immature ovine oocytes were exposed to 1% alcohol in the presence or absence of 25 μM ALA during oocyte maturation. The cumulus expansion index, intracellular reactive oxygen species (ROS), and thiol content levels were assessed in matured oocytes of various treatment groups. Consequently, the blastocyst formation rate of matured oocytes in various treatment groups were assessed. In addition, total cell number (TCN), cell allocation, DNA fragmentation, and relative gene expression of interested genes were assessed in resultant blastocysts.ResultsThe results revealed that alcohol significantly reduced cumulus cells (CCs) expansion index and blastocyst yield and rate of apoptosis in resultant embryos. Addition of 25 μM ALA to 1% ethanol during oocyte maturation decreased ROS level and elevated Thiolcontent. Furthermore, supplementation of maturation medium with ALA attenuated the effect of 1% ethanol and significantly increased the blastocyst formation and hatching rate as compared to control and ethanol groups. In addition, the quality of blastocysts produced in ALA+ethanol was improved based on the low number of TUNEL positive cells, the increased expression level of mRNA for pluripotency, and anti-oxidant markers, and decreased expression of apoptotic genes.ConclusionThe current findings demonstrate that ALA can diminish the effect of ethanol, possibly by decreasing the ROS level and increasing Thiolcontent during oocyte maturation. Using the ALA supplement may have implications in protecting oocytes from alcohol toxicity in affected patients.

| S-EPMC8196229 | biostudies-literature

Morphology-dependent titanium dioxide nanoparticle-induced keratinocyte toxicity and exacerbation of allergic contact dermatitis.

Project description:Titanium dioxide (TiO2) nanoparticles are commonly found in consumer products, such as sunscreens, and human dermal exposures are relatively high. Research suggests potential differences in the toxicity of anatase and rutile crystalline forms of TiO2. Additionally, transition metal dopants are frequently used to enhance physicochemical properties of TiO2, and the toxicity of these nanoparticles are not extensively studied. Therefore, this work examined the keratinocyte toxicity and in vivo skin allergy responses after treatment with 30 nm anatase, 30 nm rutile, or <100 nm Mn-doped TiO2 nanoparticles. After a 24-hour exposure, there were no differences in keratinocyte cytotoxicity; however, Mn-doped TiO2 nanoparticles induced significant in vitro ROS generation and in vivo skin swelling responses in a model of allergic contact dermatitis.

| S-EPMC7643926 | biostudies-literature

Doxorubicin and resveratrol co-delivery nanoparticle to overcome doxorubicin resistance.

Project description:With the extensive application of doxorubicin (DOX), DOX resistance has become one of the main obstacles to the effective treatment of breast cancer. In this paper, DOX and resveratrol (RES) were co-encapsulated in a modified PLGA nanoparticle (NPS) to overcome the DOX resistance. CLSM results indicated that DOX and RES were simultaneously delivered into the nucleus of DOX-resistant human breast cancer cells by DOX/RES-loaded NPS. Consequently, DOX/RES-loaded NPS showed significant cytotoxicity on MDA-MB-231/ADR cells and MCF-7/ADR cells. Furthermore, DOX/RES-loaded NPS could overcome DOX resistance by inhibiting the expression of drug resistance-related protein such as P-gp, MRP-1 and BCRP, and induce apoptosis through down-regulating the expression of NF-κB and BCL-2. In tumor-bearing mice, DOX/RES-loaded NPS mainly delivered DOX and RES to tumor tissue. Compared with free DOX, DOX/RES-loaded NPS significantly inhibited the DOX-resistant tumor growth in tumor-bearing mice without causing significant systemic toxicity. In a word, DOX/RES-loaded NPS could overcome the DOX resistance and had the potential in the treatment of DOX-resistant breast cancer.

| S-EPMC5059704 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data