Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway
Abstract
:1. Introduction
2. Materials and Methods
2.1. Narcissoside, Chemicals, Maintenance and Pretreatment of SH-SY5Y Cell Line
2.2. Cell Viability Assay
2.3. Mitochondrial Membrane Potential Assay of Cells
2.4. Live Cell Nuclear Staining with Hoechst 33258
2.5. Flow Cytometric Analysis of Apoptosis by FITC-Labeled Annexin-V/Propidium Iodide
2.6. Western Blot of Protein Expression
2.7. Quantitative Determination of Intracellular Reactive Oxygen Species
2.8. Determines Intracellular Glutathione (GSH) Content
2.9. Preparation of Nuclear Extract
2.10. NRF2/ARE Luciferase Reporter Assays
2.11. Electrophoretic Mobility Shift Assay (EMSA)
2.12. Transient Transfection of Small Interfering RNA of Nrf2
2.13. Measurement of MiR-200a Expression Level by qRT–PCR
2.14. Downregulation of miR200a with Anti-miR200a
2.15. C. elegans Culture and Synchronization
2.16. Food Clearance Assay Determines the Concentration of Narcissoside to Treat Nematodes
2.17. Narcissoside Pretreatment and 6-OHDA Exposure in Nematodes
2.18. Analysis of Dopaminergic Neuron Degeneration in Nematodes
2.19. Assessment of Dopamine Neuron Functionality in Nematodes with a Food Sensitivity Behavioral Test
2.20. Lifespan Assessment of Nematodes
2.21. Determining the Content of Reactive Oxygen Species in Nematodes
2.22. Determination of Glutathione Content in Nematodes
2.23. Total RNA Isolation and Quantitative Analysis of Gene Expression in Nematodes
2.24. Measurements of the Autophagy Activity of Nematodes
2.25. Statistical Analysis of the Investigation
3. Results
3.1. Narcissoside (NCS) Exhibits Protective Potential to Prevent SH-SY5Y Cells from Apoptosis Induced by 6-OHDA Exposure
3.2. Pretreatment of Narcissoside (NCS) Enhanced Level of Intracellular Glutathione (GSH) to Diminish Production of Reactive Oxygen Species (ROS) in 6-OHDA-Exposed SH-SY5Y Cells
3.3. Treatment with the GSH Synthetic Inhibitor Buthionine Sulphoximine (BSO) Abrogates the Neuroprotective Ability of Narcissoside (NCS) in 6-OHDA-Treated SH-SY5Y Cells
3.4. The Ability of Narcissoside (NCS) to Alleviate 6-OHDA-Induced Apoptosis of SH-SY5Y Cells May Be through Inhibition of p38 and JNK1/2 Mitogen-Activated Protein Kinase (MAPK) Phosphorylation and Enhancing of the Extracellular-Regulated Kinase (ERK) and Akt Pathway
3.5. The Neuroprotective Property of Narcissoside (NCS) in 6-OHDA-Exposed SH-SY5Y Cells Is Associated with the Elevation of the Activity of the Nuclear Factor Erythroid 2–Related Factor 2 (Nrf2) Pathway
3.6. Knockdown of Nrf2 Abolished the Neuroprotective Ability of Narcissoside (NCS) against Oxidative Stress and Apoptosis of SH-SY5Y Induced by 6-OHDA Exposure
3.7. Narcissoside (NCS) Inhibits Keap1 Level by Augmenting Expression of Endogenous MicroRNA-200a and Thus Enhances Nrf2 Activity
3.8. Narcissoside (NCS) Pretreatment Was Effective in Reducing Dopamine Neuron Degeneration Induced by 6-OHDA Exposure in an Animal Model of Caenorhabditis elegans
3.9. Narcissoside (NCS) Pretreatment Restores Deficits in Dopamine-Mediated Food-Sensitive Behavior in Nematodes Exposed to 6-OHDA
3.10. Narcissoside (NCS) Pretreatment Improves Shortened Lifespan of Nematodes Due to 6-OHDA Toxicity
3.11. Narcissoside (NCS) Pretreatment Declines the Level of Reactive Oxygen Species in 6-OHDA-Exposed Nematodes by Enhancing the GSH Production via Rising Expression of Skn-1, Gcs-1, and E01A2.1
3.12. Narcissoside (NCS) Significantly Reduces α-Synuclein Accumulation by Promoting Autophagy of Nematodes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Genes of C. elegans (Human) | Primer Sequences (5′-3′) | (Start→End) Size (bp) |
---|---|---|
Skn-1 (Nrf-2) | Forward: 5′-TCCACCAGCATCTCCATTC-3′ Reverse: 5′-ACTTCTCCATAGCACATCAATC-3′ | (480–600) 121 |
gcs-1 (Gclc) | Forward: 5′-GTTACAAGCCGAAGAGCAG-3′ Reverse: 5′-TGAAGCAGCGATGGACC-3′ | (231–361) 131 |
E01A2.1 (Gclm) | Forward: 5′-CACCAATCCAAACCTCTACTC-3′ Reverse: 5′-TCAAAAGTGGCAGCAATAGC-3′ | (882–1019) 138 |
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Fu, R.-H.; Tsai, C.-W.; Liu, S.-P.; Chiu, S.-C.; Chen, Y.-C.; Chiang, Y.-T.; Kuo, Y.-H.; Shyu, W.-C.; Lin, S.-Z. Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway. Antioxidants 2022, 11, 2089. https://doi.org/10.3390/antiox11112089
Fu R-H, Tsai C-W, Liu S-P, Chiu S-C, Chen Y-C, Chiang Y-T, Kuo Y-H, Shyu W-C, Lin S-Z. Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway. Antioxidants. 2022; 11(11):2089. https://doi.org/10.3390/antiox11112089
Chicago/Turabian StyleFu, Ru-Huei, Chia-Wen Tsai, Shih-Ping Liu, Shao-Chih Chiu, Yen-Chuan Chen, Yu-Ting Chiang, Yun-Hua Kuo, Woei-Cherng Shyu, and Shinn-Zong Lin. 2022. "Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway" Antioxidants 11, no. 11: 2089. https://doi.org/10.3390/antiox11112089