Role of mitochondrial glycerophosphate dehydrogenase (mGPDH) in prostate cancer cells
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 45, 2004 768 Reactive oxygen species (ROS) generation is characteristic of cancer cells and linked to tumor progression. Most ROS formation normally occurs as a by-product when electrons flow through Complexes I and III of the respiratory chain in mitochondria. However, the specific, endogenous mechanisms responsible for ROS production by mitochondria are poorly understood. mGPDH is involved in oxidation of cytosolic NADH by glecerophosphate shuttle which bypasses Complex I. We hypothesized that mGPDH is as another potential site for the production of ROS which plays an important role in the prostate cancer phenotype. The oxygen consumption of prostate cancer cells (LNCaP, DU145, PC3 and CL1) is significantly higher than that of normal immortalized prostate epithelial cells (PNT1A, PNT2C2) when glycerophosphate is used as a substrate. The higher oxygen consumption is inhibited by sodium oleate, a specific inhibitor of mGPDH. We also found that the production of ROS measured fluorometrically is significantly elevated with gycerophosphate than succinate in prostate cancer cells. However, the enzymatic activity of succinate cytochrome c reductase is even higher than that of glycerophosphate cytochrome c reductase. This indicates that more ROS is produced during oxidation of glycerophosphate than oxidation of succinate. Overall, these data suggest that mGPDH is an important site where the leakage of electrons leads to substantial ROS production in prostate cancer cells. Taken together these data suggest that ROS production in prostate cancer cells could be reduced by inhibiting mGPDH. Thus implicating that mGPDH could be a potential target in inhibiting prostate cancer proliferation. (This research was supported by Canadian Institute of Health Research to G. S.)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".