Engineered Sumoylation-Deficient Prdx6 Mutant Protein-Loaded Nanoparticles Provide Increased Cellular Defense and Prevent Lens Opacity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Human Lens Epithelial Cells
2.3. Generation and Validation of Mouse LECs Isolated from Lenses of Prdx6−/− and Prdx6+/+ Mice
2.4. Expression and Purification of Recombinant Protein, TAT-HA-Prdx6
2.5. Site-Directed Mutagenesis (SDM)
- ➢
- Prdx6 K 122 to R122, (K122R)
- ➢
- Prdx6 K142 to R142, (K142R)
- ➢
- Prdx6 Cysteine (C) 47 to isoleucine (IL) 47, (C47IL)
- ➢
- Prdx6 Histidine (H) 26 to Alanine (A) 26, (H26A)
- ➢
- Prdx6 Serine (S) 32 to A32, (S32A)
- ➢
- Prdx6 Aspartic Acid (D) 140 to A140, (D140A)
2.6. Coomassies Blue Staining and Western Blot Analysis
2.7. Preparation of Nanoparticles Containing TAT-HA-Prdx6 Analog
2.8. Characterization of Size and Zeta Potential of Nanoparticles
2.9. Atomic Force Microscopy (AFM) Imaging and Image Analysis of Nanoparticles
2.10. Quantification of Protein Encapsulation Efficiency (EE)
2.11. Prdx6 Analog Release Assay from Nanoparticles In Vitro
2.12. Sandwich-ELISA (Enzyme Linked Immunosorbent Assay)
2.13. Measurement of Phospholipase A2 (PLA2) Activity
2.14. Glutathione (GSH) Peroxidase Activity
2.15. Cellular Uptake of Prdx6 Protein Analog-Loaded Nanoparticles
2.16. Fluorescence Image and DAPI Staining
2.17. Quantitation of Intracellular ROS Level by H2-DCF-DA and CellROX® Deep Red Reagent
Determination of ROS Levels by H2-DCF-DA in SCR Eye Lenses Ex Vivo
2.18. Cell Viability Assay
2.19. Subconjuctival Delivery of Prdx6 Analog-NPs into SCR Ocular Lenses
2.20. Statistical Analyses
3. Results
3.1. A Schematic Diagram of Engineered TAT-HA-Prdx6 Expression Vector System and Expression Analysis of TAT-Linked Prdx6 Recombinant Proteins, TAT-HA-Prdx6WT or TAT-HA-Prdx6K122/142R or TAT-HA-Prdx6Inactive-mutant
3.2. Encapsulation and Physical Characterization of TAT-Linked Prdx6 Recombinant Proteins, TAT-HA-Prdx6WT or TAT-HA-Prdx6K122/142R or TAT-HA-Prdx6Inactive-mutant-NPs
3.3. In Vitro Release, Stability, and Activity of TAT-HA-Prdx6 Analog-Loaded PLGA-NPs and Encapsulation Efficiency
3.4. Cellular Uptake and Cytoprotective Effects of TAT-HA-Prdx6 Analog-Loaded PLGA-NPs in hLECs In Vitro
3.5. Internalization and Protective Potential of TAT-HA-Prdx6 Analog-NPs in Prdx6−/−-Deficient Mouse LECs Facing Oxidative Stress
3.6. Subconjuctival Administration of TAT-HA-Prdx6 Analog-NPs Prevented Lens Opacity and Delayed the Progression of Cataract Formation in SCRs
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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Chhunchha, B.; Kubo, E.; Kompella, U.B.; Singh, D.P. Engineered Sumoylation-Deficient Prdx6 Mutant Protein-Loaded Nanoparticles Provide Increased Cellular Defense and Prevent Lens Opacity. Antioxidants 2021, 10, 1245. https://doi.org/10.3390/antiox10081245
Chhunchha B, Kubo E, Kompella UB, Singh DP. Engineered Sumoylation-Deficient Prdx6 Mutant Protein-Loaded Nanoparticles Provide Increased Cellular Defense and Prevent Lens Opacity. Antioxidants. 2021; 10(8):1245. https://doi.org/10.3390/antiox10081245
Chicago/Turabian StyleChhunchha, Bhavana, Eri Kubo, Uday B. Kompella, and Dhirendra P. Singh. 2021. "Engineered Sumoylation-Deficient Prdx6 Mutant Protein-Loaded Nanoparticles Provide Increased Cellular Defense and Prevent Lens Opacity" Antioxidants 10, no. 8: 1245. https://doi.org/10.3390/antiox10081245
APA StyleChhunchha, B., Kubo, E., Kompella, U. B., & Singh, D. P. (2021). Engineered Sumoylation-Deficient Prdx6 Mutant Protein-Loaded Nanoparticles Provide Increased Cellular Defense and Prevent Lens Opacity. Antioxidants, 10(8), 1245. https://doi.org/10.3390/antiox10081245