Storage of Mutant Human SOD1 in Non-Neural Cells from the Type-1 Amyotrophic Lateral Sclerosis ratG93A Model Correlated with the Lysosomes’ Dysfunction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Rat Primary Fibroblasts: Isolation and Culture
2.3. Rat Bone Marrow Derived Mesenchymal Stem Cells: Isolation and Culture
2.4. Cell Proliferation
2.5. Haematoxylin/Eosin Staining
2.6. Multipotential Property of rBM-MSCs from ALS-PreS, ALS1-EndS and WT Rats
2.6.1. Osteogenic Differentiation
2.6.2. Adipogenic Differentiation
2.7. Immunofluorescences of rFFFs and rBM-MSCs from ALS-PreS, ALS1-EndS, and WT Rats
2.8. Acridine Orange Staining of rFFFs and rBM-MSCs from ALS-PreS, ALS1-EndS, and WT Rats
2.9. LysoTracker® Yellow HCK-123 Staining of rFFFs, and rBM-MSCs from ALS-PreS, ALS1-EndS and WT Rats
2.10. FITC-Dextran Staining of rFFFs, and rBM-MSCs from ALS-PreS, ALS1-EndS and WT Rats
2.11. Images Quantification
- CTCF = corrected total cell fluorescence
- cFID = cell fluorescence integrated density
- Ac = area of masked cell
- MAB = mean area of background (mean of five different ROI)
- MFB = mean fluorescence of the background (mean of five different ROI)
2.12. Subcellular Localization
2.13. Cell and Tissue Extracts
2.14. Lysosomal Enzyme Activity Assays
2.15. SDS-PAGE and Western Blotting
2.16. Statistical Analysis
3. Results
3.1. Study Model
3.2. Human Mutant SOD1* Is Overexpressed in Tissues, rFFFs, and rBM-MSCs from the ALS1 ratG93A Model
3.2.1. ALS1-Tissues
3.2.2. ALS1-rFFFs Model
3.2.3. ALS1-rBM-MSCs
3.3. The Activity of Lysosomal Glycohydrolases and the Expression of Some Relevant Proteases Are Altered in Tissues, rFFFs, and rBM-MSCs from the ALS1 ratG93A Model
3.3.1. Lysosomal Glycohydrolases and Proteases in ALS1 Tissues
3.3.2. Lysosomal Glycohydrolases and Proteases in ALS1-rFFFs- and ALS1-rBM-MSCs
3.4. Lysosomes’ Homeostasis and Size Are Highly Altered in ALS1-rFFFs Compared to ALS1-rBM-MSCs In Vitro Models
3.5. SOD1* Is Stored in the Lysosomes of ALS1-rFFFs and ALS1-rBM-MSCs In Vitro Models
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Bicchi, I.; Morena, F.; Argentati, C.; Nodari, L.R.; Emiliani, C.; Gelati, M.; Vescovi, A.L.; Martino, S. Storage of Mutant Human SOD1 in Non-Neural Cells from the Type-1 Amyotrophic Lateral Sclerosis ratG93A Model Correlated with the Lysosomes’ Dysfunction. Biomedicines 2021, 9, 1080. https://doi.org/10.3390/biomedicines9091080
Bicchi I, Morena F, Argentati C, Nodari LR, Emiliani C, Gelati M, Vescovi AL, Martino S. Storage of Mutant Human SOD1 in Non-Neural Cells from the Type-1 Amyotrophic Lateral Sclerosis ratG93A Model Correlated with the Lysosomes’ Dysfunction. Biomedicines. 2021; 9(9):1080. https://doi.org/10.3390/biomedicines9091080
Chicago/Turabian StyleBicchi, Ilaria, Francesco Morena, Chiara Argentati, Laura Rota Nodari, Carla Emiliani, Maurizio Gelati, Angelo L. Vescovi, and Sabata Martino. 2021. "Storage of Mutant Human SOD1 in Non-Neural Cells from the Type-1 Amyotrophic Lateral Sclerosis ratG93A Model Correlated with the Lysosomes’ Dysfunction" Biomedicines 9, no. 9: 1080. https://doi.org/10.3390/biomedicines9091080