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Published on: April 23, 2012
Evaluation of Metabolic Characteristics Induced by Deoxynivalenol in 3D4/21 Cells
Yu Han1, Bo Yu1, Wenao Weng1
1Laboratory of Genetic Breeding, Reproduction and Precision Livestock Farming & Hubei Provincial Center of Technology Innovation for Domestic Animal Breeding, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Abstract:
Deoxynivalenol (DON) is a common mycotoxin that causes immunosuppression in pigs. Its effects on cellular metabolism remain unclear. In this study, we investigate DON-induced metabolic alterations in porcine alveolar macrophage cell line 3D4/21 using non-targeted metabolomics. MTT assays showed DON reduced cell viability in a concentration- and time-dependent manner. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) revealed distinct metabolic profiles between control and DON-treated groups. Metabolomic analysis identified 127 differential metabolites (VIP > 1, p < 0.05), primarily in purine metabolism, glutathione metabolism, and arginine-proline metabolism. Integration with transcriptomic data confirmed that these pathways play key roles in DON-induced immunotoxicity. Specifically, changes in purine metabolism suggested disrupted nucleotide synthesis and energy balance, while glutathione depletion indicated weakened antioxidant defense. These findings provided a systems biology perspective on DON's metabolic reprogramming of immune cells and identified potential therapeutic targets to reduce mycotoxin-related immunosuppression in swine.
Insights
Deoxynivalenol (DON) mycotoxin disrupts pig immune cell metabolism, affecting purine and glutathione pathways. This research identifies key metabolic changes linked to DON-induced immunosuppression in swine.
Area of Science:
- Veterinary Immunology
- Toxicology
- Metabolomics
Background:
- Deoxynivalenol (DON) is a prevalent mycotoxin causing immunosuppression in pigs.
- The precise impact of DON on cellular metabolism, particularly in immune cells, is not fully understood.
Purpose of the Study:
- To investigate metabolic alterations induced by DON in a porcine alveolar macrophage cell line (3D4/21).
- To elucidate the role of specific metabolic pathways in DON-induced immunotoxicity using a systems biology approach.
Main Methods:
- Utilized non-targeted metabolomics to analyze metabolic profiles of 3D4/21 cells treated with DON.
- Employed MTT assays for cell viability assessment and multivariate statistical analyses (PCA, OPLS-DA) for metabolic profiling.
- Integrated metabolomic data with transcriptomic data to identify key affected pathways.
Main Results:
- DON exposure reduced cell viability in a dose- and time-dependent manner.
- Distinct metabolic profiles were observed between control and DON-treated cells, with 127 differential metabolites identified.
- Key affected pathways included purine metabolism, glutathione metabolism, and arginine-proline metabolism.
Conclusions:
- DON significantly alters cellular metabolism in porcine immune cells, impacting nucleotide synthesis, energy balance, and antioxidant defense.
- Disruptions in purine and glutathione metabolism are critical contributors to DON-induced immunotoxicity.
- These findings offer insights into therapeutic targets for mitigating mycotoxin-related immunosuppression in swine.
