Metabolic reprograming and increased inflammation by cadmium exposure following early-life respiratory syncytial virus infection-the involvement of protein S-palmitoylation
© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV re-programs metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV re-programs metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/L) in drinking water for 6 weeks (RSV+Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines and inflammatory cells were highest in the RSV+Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV+Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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Enthalten in: |
Toxicological sciences : an official journal of the Society of Toxicology - (2023) vom: 06. Nov. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Jarrell, Zachery R [VerfasserIn] |
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Links: |
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Themen: |
Dietary metal |
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Anmerkungen: |
Date Revised 31.01.2024 published: Print-Electronic Citation Status Publisher |
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doi: |
10.1093/toxsci/kfad112 |
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PPN (Katalog-ID): |
NLM364331909 |
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100 | 1 | |a Jarrell, Zachery R |e verfasserin |4 aut | |
245 | 1 | 0 | |a Metabolic reprograming and increased inflammation by cadmium exposure following early-life respiratory syncytial virus infection-the involvement of protein S-palmitoylation |
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520 | |a Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV re-programs metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV re-programs metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/L) in drinking water for 6 weeks (RSV+Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines and inflammatory cells were highest in the RSV+Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV+Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a dietary metal | |
650 | 4 | |a early life exposure | |
650 | 4 | |a environmental exposure | |
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700 | 1 | |a Lee, Choon-Myung |e verfasserin |4 aut | |
700 | 1 | |a Kim, Ki-Hye |e verfasserin |4 aut | |
700 | 1 | |a He, Xiaojia |e verfasserin |4 aut | |
700 | 1 | |a Smith, Matthew R |e verfasserin |4 aut | |
700 | 1 | |a Raha, Jannatul R |e verfasserin |4 aut | |
700 | 1 | |a Bhatnagasr, Noopur |e verfasserin |4 aut | |
700 | 1 | |a Orr, Michael |e verfasserin |4 aut | |
700 | 1 | |a Kang, Sang-Moo |e verfasserin |4 aut | |
700 | 1 | |a Chen, Yan |e verfasserin |4 aut | |
700 | 1 | |a Jones, Dean P |e verfasserin |4 aut | |
700 | 1 | |a Go, Young-Mi |e verfasserin |4 aut | |
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