Phospholipid metabolism in the MCF-7 cell cycle, regulation of phosphatidylcholine accumulation
Bibliographic record
Abstract
Cells reproduce by duplicating their components, doubling their size and dividing in two. Since phospholipids are major components of cell membranes, cells must double their phospholipid mass so that the daughter cells formed have the same membrane composition as the parent. However, the mode of phospholipid accumulation and how this is regulated within the cell cycle remained largely unknown. The objective of this project is to investigate how membrane phospholipid accumulation is coordinated and regulated in the cell cycle, with special emphasis on the accumulation of phosphatidylcholine (PC). Two synchronization protocols were developed that synchronized approximately 90% of the cells at specific points in the cell cycle. The double hydroxyurea treatment synchronized MCF-7 cells at the G1/S boundary while the combination of hydroxyurea and nocodazole blocked the cells at mitosis. Synchronized cells at different stages of the cell cycle were obtained by harvesting cells at various times after removal of the cell cycle blocking agents. Measurement of phospholipid mass at different stages of the cell cycle revealed that the contents of PC, phosphatidylethanolamine (PE) and phosphatidylinositol (PI) declined during S phase followed by a net accumulation in G2/M phase. The relative composition of PC, PE and PI remained unchanged throughout the cell cycle, suggesting that the e might be coordinated metabolism of these lipids in the cell cycle. Further studies demonstrated that the rate of incorporation of [3H]choline into PC was low in early S phase, increased from late S and throughout G2/M. The fluxes in PC synthesis correlated with changes in the activities of CTP:phosphocholine cytidylyltransferase (PCCT), cholinephosphotransferase (CPT) and the levels of membrane-associated PCCT. The results suggest that PC synthesis contributes to the fluctuation in PC levels observed during the MCF-7 cell cycle. On the other hand, there was little change in the rate of incorporation of [14C]ethanolamine into PE during S and G2/M phases. The activity of CTP:phosphoethanolamine cytidylyltransferase (PECT), the rate limiting enzyme in PE synthesis, showed little variation in the cell cycle, suggesting that the rate of PE catabolism is the dominant factor in regulating PE levels during the cell cycle. No evidence was obtained to implicate changes in cellular CTP levels in the cell cycle regulation of phospholipid synthesis. Studies on PC catabolism revealed that the rate of PC catabolism was enhanced during S phase but terminated in the G2/M phase. Taken together, our studies demonstrated that the decrease in PC content during S phase resulted from enhanced PC catabolism, while PC accumulation in G2/M was attributed to both enhanced PC biosynthesis and cessation of PC catabolism.
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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) | 0.000 | 0.000 |
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".