Regulation of cardiolipin remodeling in hypoglycemia-induced apoptosis
Bibliographic record
Abstract
Cardiolipin ís a major mitochondrial membrane phospholipid in the mammalian heaÉ and contains a primarily tetra-linoleoyl molecular species composition in this organ.The molecular remodeling of cardiolipin in the heart is essential to maintain this unique fatty acyl composition.The enzyme monolysocardiolipin acyltransferase catalyzes the acylation of monolysocardiolipin to cardiolipin in the molecular remodeling of cardiolipin in mammalian tissues.Monolysocardiolipin has been found to play a crucial role in apoptosis by binding to truncated Bid and causing the mitochondrial release of cytochrome c.Entry of a cell into hypoglycemia-induced apoptosis may be prevented when the cardiolipin molecular composition is maintained, and this maintenance may be mediated by monolysocardiolipin acyltransferase activity.The purpose of this project was to determine whether monolysocardiolipin acyltransferase activity plays a role in preventing hypoglycemia-induced damage to the cardiolipin molecule.Cardiolipin de novo biosynthesis and remodeling were examined in the surviving population of Hgc2 cardiac myoblast cells exposed to metabolic hypoxia.H9c2 cells were induced to undergo apoptosis by addition of 2-deoxyglucose to induce hypoglycemia.H9c2 cells were incubated in the absence or presence of 2-deoxyglucose for 16 hours.Dead cells were removed and the surviving population of cells were incubated with either [1,3-3H]- glycerol or ['l-14C¡-linoleic acid (bound to albumin 1:1 molar ratio) and the radioactivity incorporated into cardiolipin was determined.The cardiolipin pool il size in H9c2 cells treated with 2-deoxyglucose was also determined.In addition, the activities of the cardiolipin biosynthesis and remodeling enzymes, monolysocardiolipin acyltransferase protein and mRNA levels were determined.The [1,3-3H1-glycerol or ¡1-14C¡-linoleic acid incorporated into cardiolipin was unaltered in 2-deoxyglucose-treated cells compared to controls.Then too, the cardiolipin pool size, determined by phosphorous mass, was unaltered in these cells.In addition, the activities of the cardiolipin de novo biosynthetic enzymes were unaltered.Surprisingly, mitochondrial phospholipase Az activity was increased 33% (p<0.05) and monolysocardiolipin acyltransferase activity 1.7-fold (p<0.05) in 2-deoxyglucose{reated cells compared to controls.The increase in monolysocardiolipin acyltransferase activity was due to an elevated expression in monolysocardiolipin acyltransferase protein and this was due to increased mRNA expression.This shows that remodeling/reacylation of cardiolipin was increased in 2-deoxyglucose treated cells.Thus, a compensatory increase in monolysocardiolipin acyltransferase activity and expression occurs in order to maintain the cardiolipin pool size in H9c2 cells exposed to chemically induced hypoxia, in which phospholipase Az activity is elevated.Thus, the increase monolysocardiolipin acyltransferase is protective against accumulation of monolysocardiolipin and apoptosis.ilI
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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".