Cross-species metabolomic analysis of tau- and DDT-related toxicity.

Autor:	Kalia V; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032 USA., Niedzwiecki MM; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029 USA., Bradner JM; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032 USA., Lau FK; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032 USA., Anderson FL; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032 USA., Bucher ML; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032 USA., Manz KE; School of Engineering, Brown University, Providence, RI, 02912 USA., Schlotter AP; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032 USA., Fuentes ZC; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029 USA., Pennell KD; School of Engineering, Brown University, Providence, RI, 02912 USA., Picard M; Department of Neurology, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, 10032 USA., Walker DI; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029 USA., Hu WT; Department of Neurology, Rutgers Biomedical and Health Sciences, New Brunswick, NJ, 08901 USA., Jones DP; Division of Pulmonary, Allergy and Critical Medicine, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, 30322 USA., Miller GW; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032 USA.
Jazyk:	angličtina
Zdroj:	PNAS nexus [PNAS Nexus] 2022 May 03; Vol. 1 (2), pp. pgac050. Date of Electronic Publication: 2022 May 03 (Print Publication: 2022).
DOI:	10.1093/pnasnexus/pgac050
Abstrakt:	Exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) has been associated with increased risk of Alzheimer's disease (AD), a disease also associated with hyperphosphorylated tau (p-tau) protein aggregation. We investigated whether exposure to DDT can exacerbate tau protein toxicity in Caenorhabditiselegans using a transgenic strain that expresses human tau protein prone to aggregation by measuring changes in size, swim behavior, respiration, lifespan, learning, and metabolism. In addition, we examined the association between cerebrospinal fluid (CSF) p-tau protein-as a marker of postmortem tau burden-and global metabolism in both a human population study and in C. elegans , using the same p-tau transgenic strain. From the human population study, plasma and CSF-derived metabolic features associated with p-tau levels were related to drug, amino acid, fatty acid, and mitochondrial metabolism pathways. A total of five metabolites overlapped between plasma and C. elegans , and four between CSF and C. elegans . DDT exacerbated the inhibitory effect of p-tau protein on growth and basal respiration. In the presence of p-tau protein, DDT induced more curling and was associated with reduced levels of amino acids but increased levels of uric acid and adenosylselenohomocysteine. Our findings in C. elegans indicate that DDT exposure and p-tau aggregation both inhibit mitochondrial function and DDT exposure can exacerbate the mitochondrial inhibitory effects of p-tau aggregation. Further, biological pathways associated with exposure to DDT and p-tau protein appear to be conserved between species. (© The Author(s) 2022. Published by Oxford University Press on behalf of the National Academy of Sciences.)
Databáze:	MEDLINE
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