Dataset Information

Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.

ABSTRACT: Background:The protective effect of selenium (Se) on cadmium (Cd) toxicity is well documented, but underlying mechanisms are unclear.

Methods:Male mice fed standard diet were given Cd (CdCl₂, 18??mol/L) in drinking water with or without Se (Na₂SeO_4, 20??mol/L) for 16?weeks. Lungs were analyzed for Cd concentration, transcriptomics and metabolomics. Data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined transcriptome-metabolome-wide association study.

Results:Mice treated with Cd had higher lung Cd content (1.7?±?0.4?pmol/mg protein) than control mice (0.8?±?0.3?pmol/mg protein) or mice treated with Cd and Se (0.4?±?0.1?pmol/mg protein). Gene set enrichment analysis of transcriptomics data showed that Se prevented Cd effects on inflammatory and myogenesis genes and diminished Cd effects on several other pathways. Similarly, Se prevented Cd-disrupted metabolic pathways in amino acid metabolism and urea cycle. Integrated transcriptome and metabolome network analysis showed that Cd treatment had a network structure with fewer gene-metabolite clusters compared to control. Centrality measurements showed that Se counteracted changes in a group of Cd-responsive genes including Zdhhc11, (protein-cysteine S-palmitoyltransferase), Ighg1 (immunoglobulin heavy constant gamma-1) and associated changes in metabolite concentrations.

Conclusion:Co-administration of Se with Cd prevented Cd increase in lung and prevented Cd-associated pathway and network responses of the transcriptome and metabolome. Se protection against Cd toxicity in lung involves complex systems responses.

General significance:Environmental Cd stimulates proinflammatory and profibrotic signaling. The present results indicate that dietary or supplemental Se could be useful to mitigate Cd toxicity.

SUBMITTER: Hu X

PROVIDER: S-EPMC6188826 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.

Hu Xin X Chandler Joshua D JD Fernandes Jolyn J Orr Michael L ML Hao Li L Uppal Karan K Neujahr David C DC Jones Dean P DP Go Young-Mi YM

Biochimica et biophysica acta. General subjects 20180412 11

<h4>Background</h4>The protective effect of selenium (Se) on cadmium (Cd) toxicity is well documented, but underlying mechanisms are unclear.<h4>Methods</h4>Male mice fed standard diet were given Cd (CdCl<sub>2</sub>, 18 μmol/L) in drinking water with or without Se (Na<sub>2</sub>SeO<sub>4,</sub> 20 μmol/L) for 16 weeks. Lungs were analyzed for Cd concentration, transcriptomics and metabolomics. Data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined tran ...[more]

PMID: 29656123

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Project description:Intensive insight into the potential mechanisms of Se-induced Cd tolerance in cucumber seedlings is essential for further improvement of vegetable crop cultivation and breeding to obtain high yields and quality in Cd-contaminated soil. To reveal the ultrastructural and metabolic differences in Se-induced Cd tolerance, we examined the ultrastructures of chloroplasts and root cells and characterised 155 differentially expressed metabolites under Cd and/or Se stress using gas chromatography-mass spectrometry (GC-MS)-based metabolomics. Exogenous Se greatly relieved Cd-caused injuries to the ultrastructures of cucumber leaves and roots; for example, the shapes of chloroplasts treated with Cd + Se improved or even began to return to normal, the nuclei of root cells began to regenerate better and the chromatin was well-distributed compared with plants treated with Cd alone. Metabolite profiling revealed several intermediates of glycolysis and the tricarboxylic acid (TCA) cycle; also, some amino acids were up-accumulated in Cd + Se-treated cucumber seedlings and down-accumulated in Cd-treated cucumber seedlings, such as pyruvic acid, galactose, lactose, glutaric acid and alanine in leaves, glucose-6-phosphate and serine in roots, and lactic acid and glycine in both leaves and roots. These metabolites may play dominant roles in developing Se-mediated Cd tolerance. Moreover, a high level of sugars and polyols, amino acids and organic acids were up-accumulated in Cd-treated plants. Meanwhile, our data suggest that high accumulation of fructose, α-ketoglutaric acid, shikimic acid, fumaric acid and succinic acid in roots is a Cd-specific response, indicating that these metabolites are vital for cucumbers to develop Cd resistance. This study extends the current understanding of the mechanisms of Se in abating Cd contamination in cucumber and demonstrates that metabolomics profiling provides a more comprehensive view of the response of plants to heavy metals.

Project description:BackgroundSelenium (Se) is required for the synthesis of proteins (selenoproteins) with essential biological functions. Selenoproteins have a crucial role in the maintenance of cellular redox homeostasis in nearly all tissues, and are also involved in thyroid hormone metabolism, inflammation and immunity. Several immune processes rely on Se status and can be compromised if this element is present below the required level. Previous work has supported the notion that when Se is delivered at levels above those deemed to be the minimal required but below toxic concentrations it can have a boosting effect on the organism's immune response. Based on this concept Se-enriched supplements may represent a valuable resource for functional feeds in animal farming, including aquaculture.ResultsIn this study we tested the effects of Se supplemented as Sel-Plex during an immune challenge induced by polyinosinic:polycytidylic acid (poly(I:C)), a pathogen-associated molecular pattern (PAMP) that mimics viral infection. Trout were fed two diets enriched with 1 or 4 mg Se Kg(-1) of feed (dry weight) by Sel-Plex addition and a commercial formulation as control. The whole trout transcriptomic response was investigated by microarray and gene ontology analysis, the latter carried out to highlight the biological processes that were influenced by Sel-Plex supplementation in the head kidney (HK) and liver, the main immune and metabolic organs in fish. Overall, Sel-Plex enrichment up to 4 mg Se Kg(-1) induced an important response in the trout HK, eliciting an up-regulation of several genes involved in pathways connected with hematopoiesis and immunity. In contrast, a more constrained response was seen in the liver, with lipid metabolism being the main pathway altered by Se supplementation. Upon stimulation with poly(I:C), supplementation of 4 mg Se Kg(-1) increased the expression of principal mediators of the antiviral defences, especially IFN-γ, and down-stream molecules involved in the cell-mediated immune response.ConclusionsSupplementation of diets with 4 mg Se Kg(-1) using Sel-Plex remarkably improved the fish response to viral PAMP stimulation. Sel-Plex, being a highly bioavailable supplement of organic Se, might represent a suitable option for supplementation of fish feeds, to achieve the final aim of improving fish fitness and resistance against immune challenges.

Dataset Information

Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.

Publications

Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.

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