Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Cell Culture
2.3. SH-SY5Y Cell Differentiation
2.3.1. Differentiation to Produce Cells of a Cholinergic Phenotype
2.3.2. Differentiation to Produce Cells of a Dopaminergic Phenotype
2.4. Cytotoxicity and Cell Viability Assessment Using an MTT Assay
2.5. Bioenergetics Assays
2.5.1. Intracellular ATP Measurements
2.5.2. Mitochondrial Complexes I and III Activity Measurements
2.5.3. Mitochondrial Complex I Assay
2.5.4. Mitochondrial Complex III Assay
2.6. Lactate Production Assay
2.7. Measurements of Markers of Oxidative Stress
2.7.1. Reactive Oxygen Species (ROS) Assay
2.7.2. NF-E2-Related Factor 2 (NRf2)
2.7.3. Thiobarbituric Acid Reactive Substances (TBARS)
2.7.4. Antioxidant Enzyme Activities
2.8. Statistical Analysis
3. Results
3.1. The Cytotoxic Effects of Paraquat, Rotenone, and MPTP
3.2. Bioenergetic Analysis of the Effects of Paraquat, Rotenone, and MPTP
Enzyme Kinetic Effects of Paraquat, Rotenone, and MPTP
3.3. The Effects of Paraquat, Rotenone, and MPTP on Cellular Oxidative Stress
4. Discussion
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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3 h | 6 h | 12 h | 24 h | 48 h | |
---|---|---|---|---|---|
PQ | |||||
SH-SY5Y | 5676 (3878–8306) | 2463 (1735–3494) | 222.3 (183.1–270) | 35.5 (30.4–41.4) | 6.7 (5.9–7.5) |
DA | 1612 (1228–2117) | 495.7 (399.3–615.5) | 72.91 (62.5–85.1) | 13.9 (11.9–16.4) | 1.4 (1.2–1.6) |
CH | 5804 (4243–7938) | 1325 (1044–1682) | 187.3 (156.1–224.7) | 27.21 (23.4–31.6) | 3.337 (2.9–3.8) |
RO | |||||
SH-SY5Y | 2668 (1789–3979) | 1982 (1423–2760) | 706.4 (551.1–905.5) | 150.7 (119.3–165.9) | 38 (33.4–43.3) |
DA | 3291 (2278–4753) | 1441 (1083–1917) | 359.4 (289.4–446.2) | 90.3 (75.2–108.3) | 23.4 (20.4–26.8) |
CH | 4524 (3157–6483) | 1590 (1246–2029) | 586.8 (479.1–718.8) | 123 (115–153.9) | 38.2 (33.4–43.7) |
MPTP | |||||
SH-SY5Y | 2668 (1789–3979) | 1982 (1423–2760) | 706.4 (551.1–905.5) | 150.7 (119.3–165.9) | 38 (33.4–43.3) |
DA | 9244 (6127–13,950) | 3961 (2944–5330) | 811.1 (649.2–1013) | 171.6 (144.6–203.7) | 39.3 (34.4–44.9) |
CH | 9420 (5713–15,530) | 3231 (2314–4511) | 1143 (867.9–1506) | 248.2 (204.9–300.7) | 66.2 (57.6–76) |
PQ | RO | MPTP | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Cell Phenotype | SH-SY5Y | DA | CH | SH-SY5Y | DA | CH | SH-SY5Y | DA | CH | |
MCI | ||||||||||
Control | Vmax | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0. | 0.5 ± 0 | 0.5 ± 0 |
Km | 38.4 ± 4.9 | 38.4 ± 4.9 | 40 ± 5.4 | 23.4 ± 4.9 | 38.4 ± 4.9 | 32.0 ± 5.4 | 38.4 ± 4.9 | 38.4 ± 4.9 | 40.0 ± 5.4 | |
10 µM | Vmax | 0.4 ± 0 | 0.3 ± 0 | 0.4 ± 0 | 0.4 ± 0 | 0.4 ± 0.1 | 0.4 ± 0 | 0.5 ± 0 | 0.4 ± 0 | 0.5 ± 0 |
Km | 49.7 ± 2.3 | 79.4 ± 2 | 51.4 ± 3.9 | 38.7 ± 5.5 | 95.8 ± 14.5 | 45.7 ± 12.4 | 40.8 ± 1.1 | 63.3 ± 12.4 | 45.3 ± 8.6 | |
EC50s | Vmax | 0.2 ± 0 | 0.1 ± 0 | 0.3 ± 0 | 0.2 ± 0 | 0.1 ± 0 | 0.17 ± 0.01 | 0.3 ± 0 | 0.2 ± 0 | 0.3 ± 0 |
Km | 113.4 ± 4.4 | 130.7 ± 12.8 | 123 ± 10.5 | 106.5 ± 7.9 | 179.2 ± 18.9 | 159.2 ± 15.5 | 97.3 ± 16.9 | 114.8 ± 17.5 | 95.6 ± 11.8 | |
MCIII | ||||||||||
Control | Vmax | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.5 ± 0 |
Km | 30.9 ± 1.7 | 29.4 ± 1.3 | 32.9 ± 2.4 | 29.1 ± 1.4 | 33.8 ± 1.4 | 32.9 ± 2.4 | 34.3 ± 1.9 | 29.1 ± 1.4 | 32.9 ± 2.4 | |
10 µM | Vmax | 0.4 ± 0 | 0.4 ± 0 | 0.5 ± 0 | 0.5 ± 0 | 0.4 ± 0 | 0.5 ± 0 | 0.4 ± 0 | 0.4 ± 0.1 | 0.5 ± 0 |
Km | 44.1 ± 3.1 | 54.9 ± 6.3 | 52.3 ± 4.8 | 35.2 ± 1.5 | 45.9 ± 2.8 | 39.8 ± 3.3 | 37.2 ± 1.1 | 70.6 ± 15.8 | 40.1 ± 2.9 | |
EC50s | Vmax | 0.3 ± 0 | 0.3 ± 0.1 | 0.3 ± 0.1 | 0.5 ± 0 | 0.4 ± 0 | 0.4 ± 0.1 | 0.2 ± 0 | 0.2 ± 0 | 0.3 ± 0.1 |
Km | 73.9 ± 13.2 | 81.6 ± 18.4 | 92.8 ± 19.2 | 41 ± 5.5 | 52.8 ± 9.2 | 43.7 ± 6.1 | 92.9 ± 21 | 115.4 ± 23.2 | 99.6 ± 23.4 |
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Elmorsy, E.; Al-Ghafari, A.; Al Doghaither, H.; Hashish, S.; Salama, M.; Mudyanselage, A.W.; James, L.; Carter, W.G. Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells. Brain Sci. 2023, 13, 1717. https://doi.org/10.3390/brainsci13121717
Elmorsy E, Al-Ghafari A, Al Doghaither H, Hashish S, Salama M, Mudyanselage AW, James L, Carter WG. Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells. Brain Sciences. 2023; 13(12):1717. https://doi.org/10.3390/brainsci13121717
Chicago/Turabian StyleElmorsy, Ekramy, Ayat Al-Ghafari, Huda Al Doghaither, Sara Hashish, Mohamed Salama, Anusha W. Mudyanselage, Lipta James, and Wayne G. Carter. 2023. "Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells" Brain Sciences 13, no. 12: 1717. https://doi.org/10.3390/brainsci13121717