Heavy Metal Exposure-Mediated Dysregulation of Sphingolipid Metabolism
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Cell Toxicity Assay (MTT Assay)
2.3. Western Blot
2.4. Real-Time PCR
2.5. Cell Viability and Proliferation Assay
2.6. Human Lung (3D)-Perfusion Bioreactor
2.7. Sample Preparation and Extraction of Lipids for Lipidomics Analyses
2.8. LC-MS/MS of Sphingolipids
2.9. Immunofluorescent Staining
2.10. Measurement of Cellular Oxidative Stress
2.11. GeoMx Digital Spatial Profiling
2.12. Statistical Analysis
3. Results
3.1. Exposure to a High Dose of HM Induces Viability Changes in a Dose-Dependent Manner in Lung Epithelial Cells
3.2. Exposure to HM Alters Sphingolipid Metabolic Pathways in a Dose-Dependent Manner in Lung Epithelial Cells
3.3. Exposure to HM Induces Time-Dependent Changes in the Sphingolipid Metabolic Pathways in Lung Epithelial Cells
3.4. Exposure to HM Alters the Expression of Sphingolipid Metabolizing Enzymes at the Transcript Level
3.5. HM Exposure Induces Epithelial Cell-Derived Anti-Apoptotic Sphingolipid Metabolites via the Salvage and De Novo Synthesis Pathways
3.6. Exposure to HM Leads to a Limited Induction of Apoptosis in Epithelial Cells
3.7. HM Exposure in Human Lung Tissues Alters Expression of the Sphingolipid Enzymatic Pathway
3.8. Inhibition of De Novo Synthesis and Induction of Salvage Pathway-Mediated Regulation of Sphingolipid Metabolism in HM-Exposed Lung Tissues
3.9. Exposure to HM Leads to Increased Expression of SPHK1 in Epithelial Cells and Other Structural Cells in Human Lung Tissues
3.10. Upregulation of Oxidative Stress with HM Exposure
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ahmad, S.; Single, S.; Liu, Y.; Hough, K.P.; Wang, Y.; Thannickal, V.J.; Athar, M.; Goliwas, K.F.; Deshane, J.S. Heavy Metal Exposure-Mediated Dysregulation of Sphingolipid Metabolism. Antioxidants 2024, 13, 978. https://doi.org/10.3390/antiox13080978
Ahmad S, Single S, Liu Y, Hough KP, Wang Y, Thannickal VJ, Athar M, Goliwas KF, Deshane JS. Heavy Metal Exposure-Mediated Dysregulation of Sphingolipid Metabolism. Antioxidants. 2024; 13(8):978. https://doi.org/10.3390/antiox13080978
Chicago/Turabian StyleAhmad, Shaheer, Sierra Single, Yuelong Liu, Kenneth P. Hough, Yong Wang, Victor J. Thannickal, Mohammad Athar, Kayla F. Goliwas, and Jessy S. Deshane. 2024. "Heavy Metal Exposure-Mediated Dysregulation of Sphingolipid Metabolism" Antioxidants 13, no. 8: 978. https://doi.org/10.3390/antiox13080978