Energy starvation in daphnia magna from exposure to a lithium cobalt oxide nanomaterial

Nicholas J. Niemuth; Becky J. Curtis; Elizabeth D. Laudadio; Elena Sostare; Evan A. Bennett; Nicklaus J. Neureuther; Aurash A. Mohaimani; Angela Schmoldt; Eric D. Ostovich; Mark R. Viant; Robert J. Hamers; Rebecca D. Klaper

doi:10.1021/acs.chemrestox.1c00189

Energy starvation in daphnia magna from exposure to a lithium cobalt oxide nanomaterial

Nicholas J. Niemuth, Becky J. Curtis, Elizabeth D. Laudadio, Elena Sostare, Evan A. Bennett, Nicklaus J. Neureuther, Aurash A. Mohaimani, Angela Schmoldt, Eric D. Ostovich, Mark R. Viant, Robert J. Hamers, Rebecca D. Klaper^*

^*Corresponding author for this work

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Abstract

Growing evidence across organisms points to altered energy metabolism as an adverse outcome of metal oxide nanomaterial toxicity, with a mechanism of toxicity potentially related to the redox chemistry of processes involved in energy production. Despite this evidence, the significance of this mechanism has gone unrecognized in nanotoxicology due to the field's focus on oxidative stress as a universal-but nonspecific-nanotoxicity mechanism. To further explore metabolic impacts, we determined lithium cobalt oxide's (LCO's) effects on these pathways in the model organism Daphnia magna through global gene-expression analysis using RNA-Seq and untargeted metabolomics by direct-injection mass spectrometry. Our results show that a sublethal 1 mg/L 48 h exposure of D. magna to LCO nanosheets causes significant impacts on metabolic pathways versus untreated controls, while exposure to ions released over 48 h does not. Specifically, transcriptomic analysis using DAVID indicated significant enrichment (Benjamini-adjusted p ≤0.0.5) in LCO-exposed animals for changes in pathways involved in the cellular response to starvation (25 genes), mitochondrial function (70 genes), ATP-binding (70 genes), oxidative phosphorylation (53 genes), NADH dehydrogenase activity (12 genes), and protein biosynthesis (40 genes). Metabolomic analysis using MetaboAnalyst indicated significant enrichment (?-adjusted p <0.1) for changes in amino acid metabolism (19 metabolites) and starch, sucrose, and galactose metabolism (7 metabolites). Overlap of significantly impacted pathways by RNA-Seq and metabolomics suggests amino acid breakdown and increased sugar import for energy production. Results indicate that LCO-exposed Daphnia respond to energy starvation by altering metabolic pathways, both at the gene expression and metabolite levels. These results support altered energy production as a sensitive nanotoxicity adverse outcome for LCO exposure and suggest negative impacts on energy metabolism as an important avenue for future studies of nanotoxicity, including for other biological systems and for metal oxide nanomaterials more broadly.

Original language	English
Pages (from-to)	2287-2297
Number of pages	11
Journal	Chemical Research in Toxicology
Volume	34
Issue number	11
Early online date	1 Nov 2021
DOIs	https://doi.org/10.1021/acs.chemrestox.1c00189
Publication status	Published - 15 Nov 2021

Bibliographical note

Funding Information:
This material is based upon the work supported by the National Science Foundation under Grant no. CHE-2001611, the NSF Center for Sustainable Nanotechnology. The CSN is part of the Centers for Chemical Innovation Program. This project used the UW-Milwaukee Great Lakes Genomics Center for RNA isolation, Illumina NovaSeq RNA-sequencing, and bioinformatics services. Metabolomics experiments were carried out in the Environmental Metabolomics Research Laboratory at the University of Birmingham.

ASJC Scopus subject areas

Toxicology

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NiemuthNJ2021Energy
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.chemrestox.1c00189
Accepted author manuscript, 586 KB
NiemuthNJ2021Energy_supplementary_information
This document is the Accepted Manuscript version (supplementary information) of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.chemrestox.1c00189
Accepted author manuscript, 492 KB

Cite this

Niemuth, N. J., Curtis, B. J., Laudadio, E. D., Sostare, E., Bennett, E. A., Neureuther, N. J., Mohaimani, A. A., Schmoldt, A., Ostovich, E. D., Viant, M. R., Hamers, R. J., & Klaper, R. D. (2021). Energy starvation in daphnia magna from exposure to a lithium cobalt oxide nanomaterial. Chemical Research in Toxicology, 34(11), 2287-2297. https://doi.org/10.1021/acs.chemrestox.1c00189

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title = "Energy starvation in daphnia magna from exposure to a lithium cobalt oxide nanomaterial",

abstract = "Growing evidence across organisms points to altered energy metabolism as an adverse outcome of metal oxide nanomaterial toxicity, with a mechanism of toxicity potentially related to the redox chemistry of processes involved in energy production. Despite this evidence, the significance of this mechanism has gone unrecognized in nanotoxicology due to the field's focus on oxidative stress as a universal-but nonspecific-nanotoxicity mechanism. To further explore metabolic impacts, we determined lithium cobalt oxide's (LCO's) effects on these pathways in the model organism Daphnia magna through global gene-expression analysis using RNA-Seq and untargeted metabolomics by direct-injection mass spectrometry. Our results show that a sublethal 1 mg/L 48 h exposure of D. magna to LCO nanosheets causes significant impacts on metabolic pathways versus untreated controls, while exposure to ions released over 48 h does not. Specifically, transcriptomic analysis using DAVID indicated significant enrichment (Benjamini-adjusted p ≤0.0.5) in LCO-exposed animals for changes in pathways involved in the cellular response to starvation (25 genes), mitochondrial function (70 genes), ATP-binding (70 genes), oxidative phosphorylation (53 genes), NADH dehydrogenase activity (12 genes), and protein biosynthesis (40 genes). Metabolomic analysis using MetaboAnalyst indicated significant enrichment (?-adjusted p <0.1) for changes in amino acid metabolism (19 metabolites) and starch, sucrose, and galactose metabolism (7 metabolites). Overlap of significantly impacted pathways by RNA-Seq and metabolomics suggests amino acid breakdown and increased sugar import for energy production. Results indicate that LCO-exposed Daphnia respond to energy starvation by altering metabolic pathways, both at the gene expression and metabolite levels. These results support altered energy production as a sensitive nanotoxicity adverse outcome for LCO exposure and suggest negative impacts on energy metabolism as an important avenue for future studies of nanotoxicity, including for other biological systems and for metal oxide nanomaterials more broadly. ",

author = "Niemuth, {Nicholas J.} and Curtis, {Becky J.} and Laudadio, {Elizabeth D.} and Elena Sostare and Bennett, {Evan A.} and Neureuther, {Nicklaus J.} and Mohaimani, {Aurash A.} and Angela Schmoldt and Ostovich, {Eric D.} and Viant, {Mark R.} and Hamers, {Robert J.} and Klaper, {Rebecca D.}",

note = "Funding Information: This material is based upon the work supported by the National Science Foundation under Grant no. CHE-2001611, the NSF Center for Sustainable Nanotechnology. The CSN is part of the Centers for Chemical Innovation Program. This project used the UW-Milwaukee Great Lakes Genomics Center for RNA isolation, Illumina NovaSeq RNA-sequencing, and bioinformatics services. Metabolomics experiments were carried out in the Environmental Metabolomics Research Laboratory at the University of Birmingham.",

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doi = "10.1021/acs.chemrestox.1c00189",

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AU - Niemuth, Nicholas J.

AU - Curtis, Becky J.

AU - Laudadio, Elizabeth D.

AU - Sostare, Elena

AU - Bennett, Evan A.

AU - Neureuther, Nicklaus J.

AU - Mohaimani, Aurash A.

AU - Schmoldt, Angela

AU - Ostovich, Eric D.

AU - Viant, Mark R.

AU - Hamers, Robert J.

AU - Klaper, Rebecca D.

N1 - Funding Information: This material is based upon the work supported by the National Science Foundation under Grant no. CHE-2001611, the NSF Center for Sustainable Nanotechnology. The CSN is part of the Centers for Chemical Innovation Program. This project used the UW-Milwaukee Great Lakes Genomics Center for RNA isolation, Illumina NovaSeq RNA-sequencing, and bioinformatics services. Metabolomics experiments were carried out in the Environmental Metabolomics Research Laboratory at the University of Birmingham.

PY - 2021/11/15

Y1 - 2021/11/15

N2 - Growing evidence across organisms points to altered energy metabolism as an adverse outcome of metal oxide nanomaterial toxicity, with a mechanism of toxicity potentially related to the redox chemistry of processes involved in energy production. Despite this evidence, the significance of this mechanism has gone unrecognized in nanotoxicology due to the field's focus on oxidative stress as a universal-but nonspecific-nanotoxicity mechanism. To further explore metabolic impacts, we determined lithium cobalt oxide's (LCO's) effects on these pathways in the model organism Daphnia magna through global gene-expression analysis using RNA-Seq and untargeted metabolomics by direct-injection mass spectrometry. Our results show that a sublethal 1 mg/L 48 h exposure of D. magna to LCO nanosheets causes significant impacts on metabolic pathways versus untreated controls, while exposure to ions released over 48 h does not. Specifically, transcriptomic analysis using DAVID indicated significant enrichment (Benjamini-adjusted p ≤0.0.5) in LCO-exposed animals for changes in pathways involved in the cellular response to starvation (25 genes), mitochondrial function (70 genes), ATP-binding (70 genes), oxidative phosphorylation (53 genes), NADH dehydrogenase activity (12 genes), and protein biosynthesis (40 genes). Metabolomic analysis using MetaboAnalyst indicated significant enrichment (?-adjusted p <0.1) for changes in amino acid metabolism (19 metabolites) and starch, sucrose, and galactose metabolism (7 metabolites). Overlap of significantly impacted pathways by RNA-Seq and metabolomics suggests amino acid breakdown and increased sugar import for energy production. Results indicate that LCO-exposed Daphnia respond to energy starvation by altering metabolic pathways, both at the gene expression and metabolite levels. These results support altered energy production as a sensitive nanotoxicity adverse outcome for LCO exposure and suggest negative impacts on energy metabolism as an important avenue for future studies of nanotoxicity, including for other biological systems and for metal oxide nanomaterials more broadly.

AB - Growing evidence across organisms points to altered energy metabolism as an adverse outcome of metal oxide nanomaterial toxicity, with a mechanism of toxicity potentially related to the redox chemistry of processes involved in energy production. Despite this evidence, the significance of this mechanism has gone unrecognized in nanotoxicology due to the field's focus on oxidative stress as a universal-but nonspecific-nanotoxicity mechanism. To further explore metabolic impacts, we determined lithium cobalt oxide's (LCO's) effects on these pathways in the model organism Daphnia magna through global gene-expression analysis using RNA-Seq and untargeted metabolomics by direct-injection mass spectrometry. Our results show that a sublethal 1 mg/L 48 h exposure of D. magna to LCO nanosheets causes significant impacts on metabolic pathways versus untreated controls, while exposure to ions released over 48 h does not. Specifically, transcriptomic analysis using DAVID indicated significant enrichment (Benjamini-adjusted p ≤0.0.5) in LCO-exposed animals for changes in pathways involved in the cellular response to starvation (25 genes), mitochondrial function (70 genes), ATP-binding (70 genes), oxidative phosphorylation (53 genes), NADH dehydrogenase activity (12 genes), and protein biosynthesis (40 genes). Metabolomic analysis using MetaboAnalyst indicated significant enrichment (?-adjusted p <0.1) for changes in amino acid metabolism (19 metabolites) and starch, sucrose, and galactose metabolism (7 metabolites). Overlap of significantly impacted pathways by RNA-Seq and metabolomics suggests amino acid breakdown and increased sugar import for energy production. Results indicate that LCO-exposed Daphnia respond to energy starvation by altering metabolic pathways, both at the gene expression and metabolite levels. These results support altered energy production as a sensitive nanotoxicity adverse outcome for LCO exposure and suggest negative impacts on energy metabolism as an important avenue for future studies of nanotoxicity, including for other biological systems and for metal oxide nanomaterials more broadly.

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Energy starvation in daphnia magna from exposure to a lithium cobalt oxide nanomaterial

Abstract

Bibliographical note

ASJC Scopus subject areas

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