The significance of enzyme 3-Ã-hydroxysterol - delta24 reductase in cholesterol biosynthesis and steroidogenesis: an «in vitro» model to study Desmosterolosis
Bibliographic record
Abstract
Desmosterolosis is an autosomal recessive condition in which affected individuals lack expression of the final enzyme in the cholesterol biosynthetic pathway, 3β-hydroxyΔ²4cholesterol reductase (DHCR24). The enzyme is responsible for converting desmosterol to cholesterol. It is characterized by several congenital abnormalities, as well as high circulating levels of desmosterol accompanied by hypocholesterolemia. This study was intended to examine the molecular disruptions involved in desmosterolosis and determine the potential impact on steroidogenesis using an in vitro approach. Due to the importance of cholesterol in cell-signaling and cell membrane integrity, it was found that desmosterol was a poor substitute for cholesterol in cell membranes. Cells deprived of cholesterol for 45 minutes rapidly underwent morphological changes and presumably became apoptotic. This effect was potentiated in cells with DHCR24 knock-down. Additionally, cells responded by increasing levels of cholesterol biosynthetic factors such as, SREBP1, SREBP2, SCAP, S1P, as well as the enzyme HMG Co A reductase all of which were measured using real-time PCR. The increase in these transcripts indicates that desmosterol cannot be sensed by the sterol sensing domain (SSD). Following cholesterol repletion, cells were able to restore a certain level normalcy in terms of morphology and the production of the transcripts listed above. Cholesterol is required for steroidogenesis in the adrenal cortex. We examined whether or not desmosterol could be used as a steroidogenic substrate. We measured levels of steroidogenic acute regulatory protein (StAR) as well as measured cortisol production with DHCR24 knock-down following cholesterol depletion and repletion with and without trophic stimulation. We found that in cells stimulated with vasoactive intestinal polypeptide, devoid of cholesterol and with endogenous synthesis impaired at the leve
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".