Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer
Abstract
:1. Introduction
2. Results
2.1. Patient Demographics and Biopsy Pathology
2.2. The Oxidative Phosphorylation (OXPHOS) Rate of CII (PCII) Is Higher Than That of CI (PCI) in Non-Malignant Tissue
2.3. PCa GS Grade Enhances CII Flux with Increased L/P Coupling Ratio
2.4. TCA Metabolomics Support Respiratory Finding of Succinate CII Dominant Flux
2.5. GS Grade Is Related to CII Forward ROS Production Rate
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Tissue Procurement and Processing
4.3. Histopathology and Immunohistochemistry
4.4. Respirometry Protocols
4.5. ROS Analysis
4.6. Targeted Metabolomics
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Respiratory State (pmol/(s·mg)) | Biopsy Paired Source | |||
---|---|---|---|---|
GS 3 + X (n = 9) | GS 4 + X (n = 6) | |||
Non-Malignant | Malignant | Non-Malignant | Malignant | |
LEAK (L) | ||||
CI (LCI) | 2.14 ± 0.32 | 2.02 ± 0.52 | 2.09 ± 0.34 | 2.16 ± 0.98 |
CII (LCII) | 4.61 ± 0.79 | 5.88 ± 1.43 | 5.27 ± 0.85 | 8.70 ± 2.58 * |
CI + CII (LCI+CII) | ||||
OXPHOS (P) | ||||
CI (PCI) | 5.49 ± 0.82 (33.19%) 1 | 5.14 ± 0.90 (24.68%) | 5.06 ± 0.62 (32.29%) | 5.34 ± 0.75 (25.05%) |
CII (PCII) | 11.26 ± 1.31 (68.08%) | 12.43 ± 1.31 (59.67%) | 10.79 ± 1.74 (68.86%) | 13.48 ± 2.85 (63.23%) |
CI + CII (PCI+CII) | 16.54 ± 1.31 | 20.83 ± 3.79 | 15.67 ± 1.61 | 21.32 ± 2.25 * |
ETS (E) | ||||
CI (ECI) | ||||
CII (ECII) | 11.98 ± 1.15 | 13.21 ± 1.43 | 11.86 ± 1.38 | 17.44 ± 3.14 |
CI + CII (ECI+CII) | 19.07 ± 1.40 | 23.72 ± 4.19 | 17.81 ± 1.38 | 23.98 ± 2.31 * |
CI + CII Protocol | CII + Rotenone Protocol | ||||
---|---|---|---|---|---|
Injection | Abbreviation | Concentration | Injection | Abbreviation | Concentration |
glutamate | G | 10 mM | rotenone | R | 0.5 µM |
malate | M | 2 mM | succinate | S | 10 mM |
ADP | D | 2.5 mM | ADP | D | 2.5 mM |
cytochrome c | Cyt C | 10 µM | cytochrome c | Cyt C | 10 µM |
pyruvate | P | 5 mM | FCCP | F | 1.5 µM |
succinate | S | 10 mM | malonate | Mna | 5 mM |
FCCP | F | 1.5 µM | Antimycin A | AA | 2.5 µM |
rotenone | R | 0.5 µM | |||
malonate | Mna | 5 mM | |||
Antimycin A | AA | 2.5 µM |
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Zhang, A.; Gupte, A.A.; Chatterjee, S.; Li, S.; Ayala, A.G.; Miles, B.J.; Hamilton, D.J. Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer. Int. J. Mol. Sci. 2022, 23, 12168. https://doi.org/10.3390/ijms232012168
Zhang A, Gupte AA, Chatterjee S, Li S, Ayala AG, Miles BJ, Hamilton DJ. Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer. International Journal of Molecular Sciences. 2022; 23(20):12168. https://doi.org/10.3390/ijms232012168
Chicago/Turabian StyleZhang, Aijun, Anisha A. Gupte, Somik Chatterjee, Shumin Li, Alberto G. Ayala, Brian J. Miles, and Dale J. Hamilton. 2022. "Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer" International Journal of Molecular Sciences 23, no. 20: 12168. https://doi.org/10.3390/ijms232012168