Plasmalogen Precursors Reverse Lipid Changes in a Barth Syndrome Cell Model
Bibliographic record
Abstract
Barth syndrome is rare X chromosome‐linked genetic disorder that is caused by mutations in tafazzin, a phospholipid‐lysophospholipid transacylase responsible for the last step of cardiolipin (CL) biosynthesis in the mitochondria. The lipid alterations in Barth syndrome include loss in total CL content, an increase in the concentration of monolysocardiolipin (MLCL) and a greater heterogeneity of the acyl chains of CL. These changes are so characteristic of Barth syndrome that they have become the basis of diagnostic tests. Recently, one of us has demonstrated that the major change in the lipid composition of organs that have been depleted of tafazzin is the loss of plasmalogens. In several disease states where loss of plasmalogens has been reported, the condition could be reversed by the administration of plasmalogen precursors. Hence, we hypothesized that administration of plasmalogen precursors could reverse the phenotype of Barth syndrome. Here, we present the high‐resolution 31 P‐NMR phospholipidomic study of the total lipid extract of a Barth syndrome cell model, i.e ., lymphoblasts derived from Barth syndrome patients compared with controls in absence and presence of feeding plasmalogen precursors. Lymphoblasts derived from Barth patients in comparison to controls are ideal for studies of the mechanism as it is a single cell type that can be grown in culture and have all the characteristics of cells from patients with this Syndrome. In agreement with previous results we observed a marked decrease in plasmalogen in Barth lymphoblasts compared to controls together with other lipid alterations reported in those cells. Furthermore, as expected, feeding the cells with plasmalogen precursors restored plasmalogen levels. However, to our surprise the feeding also markedly increased the level of CL. Moreover, we also could show that the CL increase is not a consequence of a decrease in CL hydrolysis by a phospholipase (degradation) as evinced by the lack of MLCL accumulation in cells fed with plasmalogen precursors. In summary, we are able to reverse, at least in part, the lipid changes associated with Barth syndrome by feeding our cell model with plasmalogen precursors. We wish to extend these findings to determine how these changes in lipid composition affect the functioning of their mitochondria. This may present a simple and rapid process to bring these new strategies to the clinic since the precursors we are using are non‐toxic and have been administered to humans for other purposes. Support or Funding Information An award from the Barth Syndrome Foundation, Inc. and the Barth Syndrome Foundation of Canada. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.000 |
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".