Extracellular Vesicles and Their Renin–Angiotensin Cargo as a Link between Metabolic Syndrome and Parkinson’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Experiments
2.2. Isolation of EVs from Animal Serum
2.3. EV Characterization by Western Blot, Transmission Electron Microscopy (TEM), and Esterase Activity
2.4. EV-RAS Protein Analysis by Exoview®
2.5. EV-mRNA Cargo Analysis
2.6. Cultures of the N27 Dopaminergic Cell Line and the C6 Astrocytic Cell Line
2.7. EV Labeling and Uptaking by the N27 Dopaminergic Cell Line and the C6 Astrocytic Cell Line
2.8. Culture Treatments and MTT Assay
2.9. NADPH-Oxidase Activity and Cytokine Levels
2.10. Analysis of Cell mRNA Expression in Recipient Cells
2.11. Statistical Analysis
3. Results
3.1. Isolation and Characterization of EVs from Rat Serum and Effects of MetS and Candesartan Treatment
3.2. mRNA Expression of RAS Components in Serum EVs and Effects of Treatment of MetS Rats with Candesartan
3.3. RAS Component Proteins in EVs and Effects of MetS and Treatment with Candesartan
3.4. mRNA Expression of Pro-Inflammatory Cytokines and Pro-Oxidative Markers in Serum EVs and Effects of Treatment of MetS Rats with Candesartan
3.5. Uptake of EVMetS by the N27 Dopaminergic Cell Line and the C6 Astrocytic Cell Line In Vitro
3.6. EVMetS Enhance N27 Dopaminergic Cell Line Death in Cell Cultures Mediated by AT1 Receptor Activation
3.7. EVMetS Modulate the C6 Astrocytic Cell Line and N27 Dopaminergic Cell Line Function through AT1 Receptor Activation
3.8. EVMetS Uptake Leads to RAS Dysregulation in Cultured N27 Dopaminergic Cell Line and C6 Astrocytic Cell Line
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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Genes | Primers (5′-3′) | Accession Number | Product Length (bps) |
---|---|---|---|
Ace2 | F: GTGGAGGTGGATGGTCTTTCAGG; R: CACCAACGATCTCCCGCTTCA | NM_001012006.2 | 86 |
Actb | F: TCGTGCGTGACATTAAAGAG; R: TGCCACAGGATTCCATACC | NM_031144.3 | 198 |
Agt | F: GAGTGAGGCAAGAGGTGTA; R: TCCAACGATCCAAGGTAGAA | NM_134432.2 | 90 |
Agtr1a | F: GCCAAGCCAGCCATCAGC; R: TTCAACCTCTACGCCAGTGTG; | NM_030985.4 | 149 |
Atp6ap2 (Prr) | F: TGGTGGGAATGCAGTGGTAGAG; R: GGGACTTTGGGTGTTCTCTTGTT | NM_001007091.1 | 109 |
Cybb (Gp91-phox) | F: ATCTTGCTGCCAGTGTGTCG; R: AATGGTGTGAATGGCCGTGTG | NM_023965.2 | 153 |
Gapdh | F: ACATACTCAGCACCAGCAT; R: GCAAGTTCAACGGCACAGT | NM_017008.4 | 124 |
Gfap | F: TGGAGGTGGAGAGGGACAATC; R: CTCCAGATCCACACGAGCCAA | NM_017009.2 | 152 |
Il1b | F: GGCAACTGTCCCTGAACTCA; R: TGTCGAGATGCTGCTGTGAGA | NM_031512.2 | 170 |
Il6 | F: TGGTATCCTCTGTGAAGTCTC; R: CAGCCAGTTGCCTTCTTG | NM_012589.2 | 91 |
Mas1 | F: TCCCCAGACCAGTCATCCT; R: TGCTGGAGGTATTCATGGCTT | NM_012757.2 | 122 |
Ncf1 (P47-phox) | F: TGTTCCTGGTTAAGTGGCAGGA; R: CTGGGAGCTGGGAGGTGAG | NM_053734.2 | 157 |
Tnf | F: CACGTCGTAGCAAACCACCA; R: GGTTGTCTTTGAGATCCATGCCA | NM_012675.3 | 97 |
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Pedrosa, M.A.; Labandeira, C.M.; Lago-Baameiro, N.; Valenzuela, R.; Pardo, M.; Labandeira-Garcia, J.L.; Rodriguez-Perez, A.I. Extracellular Vesicles and Their Renin–Angiotensin Cargo as a Link between Metabolic Syndrome and Parkinson’s Disease. Antioxidants 2023, 12, 2045. https://doi.org/10.3390/antiox12122045
Pedrosa MA, Labandeira CM, Lago-Baameiro N, Valenzuela R, Pardo M, Labandeira-Garcia JL, Rodriguez-Perez AI. Extracellular Vesicles and Their Renin–Angiotensin Cargo as a Link between Metabolic Syndrome and Parkinson’s Disease. Antioxidants. 2023; 12(12):2045. https://doi.org/10.3390/antiox12122045
Chicago/Turabian StylePedrosa, Maria A., Carmen M. Labandeira, Nerea Lago-Baameiro, Rita Valenzuela, Maria Pardo, Jose Luis Labandeira-Garcia, and Ana I. Rodriguez-Perez. 2023. "Extracellular Vesicles and Their Renin–Angiotensin Cargo as a Link between Metabolic Syndrome and Parkinson’s Disease" Antioxidants 12, no. 12: 2045. https://doi.org/10.3390/antiox12122045