Downregulation of Iron–Sulfur Cluster Biogenesis May Contribute to Hyperglycemia-Mediated Diabetic Peripheral Neuropathy in Murine Models
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Glucose and Insulin Tolerance Tests
2.3. Hot Plate Test
2.4. Rotarod Test
2.5. Beam-Walk Test
2.6. Electron Microscopy
2.7. Histological Assays
2.8. Ferrozine Iron Assays
2.9. Labile Iron Pool (LIP) Measurements
2.10. The Enzymatic Activities of Aconitase, Complexes I and II, and Mitochondrial Membrane Potential (MMP) Levels
2.11. ROS Detection Assays
2.12. Western Blot Assays
2.13. Quantitative Real-Time PCR
2.14. Statistics Analysis
3. Results
3.1. High Glucose Downregulates Fe-S-Cluster Biogenesis and Fe-S-Containing Enzymatic Activities in RSC96 Cells
3.2. High-Glucose Treatment Increases the Cellular Labile Iron Pool and Promotes ROS Production in RSC96 Cells
3.3. Pioglitazone Treatment Increases the Expression of Genes Involved in the Biosynthesis of Fe-S Clusters and Recovers Iron Homeostasis and Redox Balance in RSC96 Cells
3.4. Rescue of Fe-S Cluster Biosynthesis by Pioglitazone Treatment Correlates Well with the Increase in the Enzymatic Activities of Fe-S Protein and with the Improvement of Iron Homeostasis and Inflammation in Sciatic Nerve
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Wu, L.; Huang, F.; Sun, Z.; Zhang, J.; Xia, S.; Zhao, H.; Liu, Y.; Yang, L.; Ding, Y.; Bian, D.; et al. Downregulation of Iron–Sulfur Cluster Biogenesis May Contribute to Hyperglycemia-Mediated Diabetic Peripheral Neuropathy in Murine Models. Antioxidants 2024, 13, 1036. https://doi.org/10.3390/antiox13091036
Wu L, Huang F, Sun Z, Zhang J, Xia S, Zhao H, Liu Y, Yang L, Ding Y, Bian D, et al. Downregulation of Iron–Sulfur Cluster Biogenesis May Contribute to Hyperglycemia-Mediated Diabetic Peripheral Neuropathy in Murine Models. Antioxidants. 2024; 13(9):1036. https://doi.org/10.3390/antiox13091036
Chicago/Turabian StyleWu, Lin, Fei Huang, Zichen Sun, Jinghua Zhang, Siyu Xia, Hongting Zhao, Yutong Liu, Lu Yang, Yibing Ding, Dezhi Bian, and et al. 2024. "Downregulation of Iron–Sulfur Cluster Biogenesis May Contribute to Hyperglycemia-Mediated Diabetic Peripheral Neuropathy in Murine Models" Antioxidants 13, no. 9: 1036. https://doi.org/10.3390/antiox13091036