Knockdown of Cardiolipin Synthase in Human Brain Microvessel Endothelial Cells Modulates Blood Brain Barrier Transport Properties
Bibliographic record
Abstract
The blood brain barrier (BBB) is formed by microvessel endothelial cells and is a restrictively permeable interface that allows transport of only specific compounds into the brain. Cardiolipin (CL) a mitochondrial (MITO) lipid is required for activity/integrity of the respiratory chain. We examined the role of CL in maintaining barrier properties of brain microvessel endothelial cells. We show that human brain capillary endothelial cells (hCMEC/D3) produce a significant proportion of their basal ATP requirement through MITO oxidative phosphorylation. siRNA knockdown (KD) of the CL biosynthetic enzyme CL synthase (CLS) significantly reduced these cells ability to increase MITO function under conditions of increased metabolic demand compared to controls. In addition, KD of CLS acted as a metabolic switch causing hCMEC/D3 cells to become more dependent on glycolysis. KD of CLS increased [3H]‐2‐deoxyglucose ([3H]‐2DG) uptake compared to controls, and this may thus serve as a mechanism to compensate for the cells reduced MITO energy production efficiency. Finally, KD of CLS did not affect movement of the permeability marker fluorescent dextran across confluent hCMEC/D3 monolayers grown on Transwell ® plates, an in vitro model for the human BBB, but caused in an increase in [3H]‐2DG transport across the monolayer compared to controls. The results suggest that brain endothelial MITO energy status play a role in regulating glucose transport across the human BBB. These observations may, in part, explain why brain capillary endothelial cells possess higher MITO content than endothelial cells derived from non‐BBB regions of the body. (Supported by NSERC and the CRC Program)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".