Subtoxic dose of lithium cobalt oxide nanosheets impacts critical molecular pathways in trout gill epithelial cells

Mensch, Arielle C.; Mitchell, Hugh D.; Markillie, Lye Meng; Laudadio, Elizabeth D.; Orbeck, Jenny K. Hedlund; Dohnálková, Alice; Schwartz, Michael P.; Hamers, Robert J.; Orr, Galya

doi:10.1039/d0en00844c

Cited by 4 publications

(22 citation statements)

References 65 publications

(84 reference statements)

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“…These functions are likely activated as part of the cellular response to the NP insult, which has been reported to include strong ROS generation and oxidative stress, DNA and heme protein damage, and energy and oxygen related imbalance. 10 , 12 , 16 , 17 This interpretation is also supported by the observation that the averaged expression level of GAPDH significantly increased in response to all exposure conditions except the nontoxic dose at 24 h ( Figure 5 ).…”

Section: Resultssupporting

confidence: 67%

“…It has been also shown that under certain conditions, GLUT1 and GLUT4 expression is regulated in opposite directions. 51 Prior observations suggesting that LCO NPs induce hypoxia and other stress responses in these cells 17 might explain the more consistent increase in the expression of GLUT1 ( Figure 5 ) while decreasing the priority of GLUT4 relative to other more critical genes for cell survival under the NP insult ( Figure 7 D).…”

Section: Resultsmentioning

confidence: 83%

“…Here we used LCO NPs from the same NP batch used in Mensch et al, 17 where a detailed characterization of the NPs is provided. Briefly, the NPs used here have stoichiometry of Li 0.87 CoO 2 , as determined by ICP-OES.…”

Section: Resultsmentioning

confidence: 99%

“…The 10 genes were selected based on previous observations using bulk RNA-seq in these cells, showing a substantial increase in their expression levels in response to LCO NPs. 17 The full names for the abbreviated genes and the key for the color-codes assigned to each gene through the manuscript are provided in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

“…These observations point to cellular attempts to restore oxygen and energy imbalance by increasing glycolysis rate and glucose import and transport. 17 , 18 However, how the cells prioritize the expression of these genes to achieve optimal cellular response and survival with limited resources under the NP insult is still unclear. More broadly, how a cell under critical stress conditions redistributes resources to restore and maintain energy balance is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Expression Patterns of Energy-Related Genes in Single Cells Uncover Key Isoforms and Enzymes That Gain Priority Under Nanoparticle-Induced Stress

Mitchell

Mensch

et al. 2022

ACS Nano

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Cellular responses to nanoparticles (NPs) have been largely studied in cell populations, providing averaged values that often misrepresent the true molecular processes that occur in the individual cell. To understand how a cell redistributes limited molecular resources to achieve optimal response and survival requires single-cell analysis. Here we applied multiplex single molecule-based fluorescence in situ hybridization (fliFISH) to quantify the expression of 10 genes simultaneously in individual intact cells, including glycolysis and glucose transporter genes, which are critical for restoring and maintaining energy balance. We focused on individual gill epithelial cell responses to lithium cobalt oxide (LCO) NPs, which are actively pursued as cathode materials in lithium-ion batteries, raising concerns about their impact on the environment and human health. We found large variabilities in the expression levels of all genes between neighboring cells under the same exposure conditions, from only a few transcripts to over 100 copies in individual cells. Gene expression ratios among the 10 genes in each cell uncovered shifts in favor of genes that play key roles in restoring and maintaining energy balance. Among these genes are isoforms that can secure and increase glycolysis rates more efficiently, as well as genes with multiple cellular functions, in addition to glycolysis, including DNA repair, regulation of gene expression, cell cycle progression, and proliferation. Our study uncovered prioritization of gene expression in individual cells for restoring energy balance under LCO NP exposures. Broadly, our study gained insight into single-cell strategies for redistributing limited resources to achieve optimal response and survival under stress.

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Section: Resultssupporting

confidence: 67%

Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression Patterns of Energy-Related Genes in Single Cells Uncover Key Isoforms and Enzymes That Gain Priority Under Nanoparticle-Induced Stress

Mitchell

Mensch

et al. 2022

ACS Nano

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Physiological Impacts on Raphidocelis subcapitata in Response to Lithiated Cobalt Oxide Nanomaterials

Ostovich

Henke

Green

et al. 2023

Enviro Toxic and Chemistry

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Complex metal oxide nanomaterials, like lithiated cobalt oxide (LCO) nanosheets, are among the most widespread classes of nanomaterials on the market. Their ubiquitous application in battery storage technology drives their production to rates of environmental significance without sufficient infrastructure for proper disposal/recycling, thus posing a risk to ecosystem health and sustainability. The present study assesses the general toxicological impacts of LCO when exposed to Raphidocelis subcapitata; physiological endpoints relating to growth and energy production are considered. Algal growth inhibition was significantly increased at concentrations as low as 0.1 µg ml −1 , while exhibiting a median effect concentration of 0.057 µg ml −1 . The average biovolume of cells was significantly enlarged at 0.01 µg ml −1 , thus indicating increased instances of cell cycle arrest in LCO-treated cells. In addition, LCO-treated cells produced significantly less carbon biomass while significantly overproducing neutral lipid content starting at 0.1 µg ml −1 , thus indicating interference with CO 2 assimilation chemistry and/or carbon partitioning. However, the relative abundance of chlorophyll was significantly increased, likely to maximize light harvesting and compensate for photosynthetic interference. Cells that were treated with dissolved Li + /Co 2+ ions did not significantly impact any of the endpoints tested, suggesting that LCO phytotoxicity is mainly induced through nano-specific mechanisms rather than ion-specific ones. These results indicate that this type of nanomaterial can significantly impact the way this alga proliferates, as well as the way it produces and stores its energy, even at lower, sublethal, concentrations. Furthermore, impairments to crucial cellular pathways, like carbon assimilation, could potentially cause implications at the ecosystem level. Thus, in future work, it will be important to characterize the molecular mechanisms of LCO at the nano-bio interface.

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Isolation Methods Influence the Protein Corona Composition on Gold-Coated Iron Oxide Nanoparticles

2022

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Upon exposure to a biological environment, nanoparticles (NPs) acquire biomolecular coatings, the most studied of which is the protein corona. This protein corona gives NPs a new biological identity that will determine various biological responses including cellular uptake, biodistribution, and toxicity. The standard method to isolate NPs from a biological matrix in order to study their coronas is centrifugation, but more gentle means of retrieval may enable deeper understanding of both irreversibly bound hard coronas and more loosely bound soft coronas. In this study, magnetic gold-coated iron oxide NPs were incubated with rainbow trout gill cell total protein extracts and mass spectrometric proteomic analysis was conducted to determine the composition of the protein coronas isolated by either centrifugation or magnetic retrieval. The number of washes were varied to strip away the soft coronas and isolate the hard corona. Hundreds of proteins were adsorbed to the NPs. Some proteins were common to all isolation methods and many others were particular to the isolation method. Some qualitative trends in protein character were discerned from quantitative proteomic analyses, but more importantly, a new kind of protein corona was identified, mixed corona, in which the labile or inert nature of the protein−NP interaction is dependent upon sample history.

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Subtoxic dose of lithium cobalt oxide nanosheets impacts critical molecular pathways in trout gill epithelial cells

Abstract: Global transcriptomics uncovered key molecular processes impacted by subtoxic dose of lithium cobalt oxide nanoparticles, indicating cellular attempts to restore energy and oxygen balance.

Cited by 4 publications

References 65 publications

Expression Patterns of Energy-Related Genes in Single Cells Uncover Key Isoforms and Enzymes That Gain Priority Under Nanoparticle-Induced Stress

Expression Patterns of Energy-Related Genes in Single Cells Uncover Key Isoforms and Enzymes That Gain Priority Under Nanoparticle-Induced Stress

Physiological Impacts on Raphidocelis subcapitata in Response to Lithiated Cobalt Oxide Nanomaterials

Isolation Methods Influence the Protein Corona Composition on Gold-Coated Iron Oxide Nanoparticles

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