Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mechanistic Differences in Cell Death Responses to Metal-Based Engineered Nanomaterials in Kupffer Cells and Hepatocytes.

ABSTRACT: The mononuclear phagocyte system in the liver is a frequent target for nanoparticles (NPs). A toxicological profiling of metal-based NPs is performed in Kupffer cell (KC) and hepatocyte cell lines. Sixteen NPs are provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences to study the toxicological effects in KUP5 (KC) and Hepa 1-6 cells. Five NPs (Ag, CuO, ZnO, SiO₂ , and V₂ O₅ ) exhibit cytotoxicity in both cell types, while SiO₂ and V₂ O₅ induce IL-1β production in KC. Ag, CuO, and ZnO induced caspase 3 generated apoptosis in both cell types is accompanied by ion shedding and generation of mitochondrial reactive oxygen species (ROS) in both cell types. However, the cell death response to SiO₂ in KC differs by inducing pyroptosis as a result of potassium efflux, caspase 1 activation, NLRP3 inflammasome assembly, IL-1β release, and cleavage of gasdermin-D. This releases pore-performing peptide fragments responsible for pyroptotic cell swelling. Interestingly, although V₂ O₅ induces IL-1β release and delays caspase 1 activation by vanadium ion interference in membrane Na⁺ /K⁺ adenosine triphosphate (ATP)ase activity, the major cell death mechanism in KC (and Hepa 1-6) is caspase 3 mediated apoptosis. These findings improve the understanding of the mechanisms of metal-based engineered nanomaterial (ENM) toxicity in liver cells toward comprehensive safety evaluation.

SUBMITTER: Wang X

PROVIDER: S-EPMC7263057 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Biological Responses to Engineered Nanomaterials: Needs for the Next Decade.

Project description:The interaction of nanomaterials with biomolecules, cells, and organisms is an enormously vital area of current research, with applications in nanoenabled diagnostics, imaging agents, therapeutics, and contaminant removal technologies. Yet the potential for adverse biological and environmental impacts of nanomaterial exposure is considerable and needs to be addressed to ensure sustainable development of nanomaterials. In this Outlook four research needs for the next decade are outlined: (i) measurement of the chemical nature of nanomaterials in dynamic, complex aqueous environments; (ii) real-time measurements of nanomaterial-biological interactions with chemical specificity; (iii) delineation of molecular modes of action for nanomaterial effects on living systems as functions of nanomaterial properties; and (iv) an integrated systems approach that includes computation and simulation across orders of magnitude in time and space.

| S-EPMC4827556 | biostudies-other

Engineered metal oxide nanomaterials inhibit corneal epithelial wound healing in vitro and in vivo.

Project description:Ocular exposure to metal oxide engineered nanomaterials (ENMs) is common as exemplified by zinc oxide (ZnO), a major constituent of sunscreens and cosmetics. The ocular surface that includes the transparent cornea and its protective tear film are common sites of exposure for metal ENMs. Despite the frequency of exposure of the ocular surface, there is a knowledge gap regarding the effects of metal oxide ENMs on the cornea in health and disease. Therefore, we studied the effects of metal oxide ENMs on the cornea in the presence or absence of injury. Cell viability of immortalized human corneal epithelial (hTCEpi) cells was assessed following treatment with 11 metal oxide ENMs with a concentration ranging from 0.5 to 250 μg/mL for 24 hours. An epithelial wound healing assay with a monolayer of hTCEpi cells was then performed using 11 metal oxide ENMs at select concentrations based on data from the viability assays. Subsequently, based on the in vitro results, in vivo testing of precorneal tear film (PTF) quantity and stability as well as a corneal epithelial wound healing were tested in the presence or absence ZnO or vanadium pentoxide (V2O5) at a concentration of 50 μg/mL. We found that WO3, ZnO, V2O5 and CuO ENMs significantly reduced hTCEpi cell viability in comparison to vehicle control or the other metal oxide ENMs tested. Furthermore, ZnO and V2O5 ENMs also significantly decreased hTCEpi cell migration. Although ZnO and V2O5 did not alter PTF parameters of rabbits in vivo, corneal epithelial wound healing was significantly delayed by topical ZnO while V2O5 did not alter wound healing. Finally, hyperspectral images confirmed penetration of ZnO and V2O5 through all corneal layers and into the iris stroma. Considering the marked epithelial toxicity and corneal penetration of ZnO, further investigations on the impact of this ENM on the eye are warranted.

| S-EPMC7062360 | biostudies-literature

Effects of Engineered Nanomaterials on Mouse Airways: Assessment of 28 Nanomaterials.

Project description:C57BL/6 mice were exposed by oropharyngeal aspiration to 28 nanomaterials including different surface functionalizations on 4 concecutive days with the dose of 10ug/day. Total RNA was collected from the mice lung biopsies after sacrificing.

2021-05-26 | GSE157266 | GEO

Toxicological Profiling of Metal Oxide Nanoparticles in Liver Context Reveals Pyroptosis in Kupffer Cells and Macrophages versus Apoptosis in Hepatocytes.

Project description:The liver and the mononuclear phagocyte system are a frequent target for engineered nanomaterials, either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. We not only observed differences between KCs and hepatocytes, but also differences in the toxicological profiles of transition-metal oxides (TMOs, e. g., Co3O4) versus rare-earth oxide (REO) NPs ( e. g., Gd2O3). While pro-oxidative TMOs induced the activation of caspases 3 and 7, resulting in apoptotic cell death in both cell types, REOs induced lysosomal damage, NLRP3 inflammasome activation, caspase 1 activation, and pyroptosis in KCs. Pyroptosis was accompanied by cell swelling, membrane blebbing, IL-1? release, and increased membrane permeability, which could be reversed by knockdown of the pore forming protein, gasdermin D. Though similar features were not seen in hepatocytes, the investigation of the cytotoxic effects of REO NPs could also be seen to affect macrophage cell lines such as J774A.1 and RAW 264.7 cells as well as bone marrow-derived macrophages. These phagocytic cell types also demonstrated features of pyroptosis and increased IL-1? production. Collectively, these findings demonstrate important mechanistic considerations that can be used for safety evaluation of metal oxides, including commercial products that are developed from these materials.

| S-EPMC5946698 | biostudies-literature

Bottom-up synthesis of protein-based nanomaterials from engineered ?-solenoid proteins.

Project description:Biomolecular self-assembly is an emerging bottom-up approach for the synthesis of novel nanomaterials. DNA and viruses have both been used to create scaffolds but the former lacks chemical diversity and the latter lack spatial control. To date, the use of protein scaffolds to template materials on the nanoscale has focused on amyloidogenic proteins that are known to form fibrils or two-protein systems where a second protein acts as a cross-linker. We previously developed a unique approach for self-assembly of nanomaterials based on engineering ?-solenoid proteins (BSPs) to polymerize into micrometer-length fibrils. BSPs have highly regular geometries, tunable lengths, and flat surfaces that are amenable to engineering and functionalization. Here, we present a newly engineered BSP based on the antifreeze protein of the beetle Rhagium inquisitor (RiAFP-m9), which polymerizes into stable fibrils under benign conditions. Gold nanoparticles were used to functionalize the RiAFP-m9 fibrils as well as those assembled from the previously described SBAFP-m1 protein. Cysteines incorporated into the sequences provide site-specific gold attachment. Additionally, silver was deposited on the gold-labelled fibrils by electroless plating to create nanowires. These results bolster prospects for programable self-assembly of BSPs to create scaffolds for functional nanomaterials.

| S-EPMC7034853 | biostudies-literature

Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials: the NIEHS Nano GO Consortium.

Project description:BackgroundEngineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity.MethodsFour laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid "functionalized" (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment.ResultsTiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice.ConclusionsENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.

| S-EPMC3672912 | biostudies-literature

MRNA-Integrative multi-omics survey of effects carbon-based engineered nanomaterials on lung derived cell-lines

Project description:In this study we exposed three human lung derived cell lines to sublethal dosages of nanomaterials for a limited amount of time. For the first time, we assessed the simultaneous effects of nanomaterials exposure on three distinct molecular layers along with their interactions in the determination of the MOA of 10 carbon based nanomaterials. By performing an integrative analysis we provide here a complete picture of the interaction between regulatory factors (DNA methylation and miRNAs) and mRNA deregulation subsequent to exposing different cellular systems to different nanomaterials.

2018-05-19 | E-MTAB-6396 | biostudies-arrayexpress

MIRNA - Integrative multi-omics survey of effects carbon-based engineered nanomaterials on lung derived cell-lines

2018-05-19 | E-MTAB-6406 | biostudies-arrayexpress

Development of reference metal and metal oxide engineered nanomaterials for nanotoxicology research using high throughput and precision flame spray synthesis approaches.

Project description:There is a growing need to develop and characterize reference metal and metal oxide engineered nanomaterials (ENMs) of high purity and tunable intrinsic properties suitable for nanotoxicology research. Here a high throughput (volume) and precision flame spray pyrolysis (FSP) approach coupled with state-of-the-art characterization techniques are utilized to generate such reference ENMs. The lab-based and industrially relevant FSP system, termed as Versatile Engineered Nanomaterials Generation System (VENGES), synthesizes the metals and metal oxides, at high throughput manner with controlled properties, such as primary particle size, aggregate diameter, shape, crystallinity, stoichiometry and surface chemistry. A nanopanel of nine reference ENMs (silica, silver, silver supported on silica, alumina, ceria and iron oxide) was synthesized and characterized using combined electron microscopy, advanced spectroscopic techniques and physical analyses (e.g., BET, XRD, TEM, pycnometry, XPS, ICP-MS and FTIR). ENMs show a high degree of chemical purity and stoichiometry, and low content of carbon residuals, and are sterile and free of bacteria and endotoxins. Further, their colloidal properties and their implication in in-vitro dosimetry have been also investigated in both environmental and test biological media. The suitability of reference ENMs and protocols developed in this study brings forth new arenas to generate reliable and reproducible toxicological data in an effort to reduce conflicting and contradicting inter-laboratory data on relative toxic effects of ENMs.

| S-EPMC6051426 | biostudies-literature

DNA-METHYLATION - Integrative multi-omics survey of effects carbon-based engineered nanomaterials on lung derived cell-lines

2018-05-19 | E-MTAB-6397 | biostudies-arrayexpress