Selective Azapeptide CD36 Ligand MPE-298 Regulates oxLDL-LOX-1-Mediated Inflammation and Mitochondrial Oxidative Stress in Macrophages
Bibliographic record
Abstract
Macrophage mitochondrial dysfunction, caused by oxidative stress, has been proposed as an essential event in the progression of chronic inflammation diseases, such as atherosclerosis. The cluster of differentiation-36 (CD36) and lectin-like oxLDL receptor-1 (LOX-1) scavenger receptors mediate macrophage uptake of oxidized low-density lipoprotein (oxLDL), which contributes to mitochondrial dysfunction by sustained production of mitochondrial reactive oxygen species (mtROS), as well as membrane depolarization. In the present study, the antioxidant mechanisms of action of the selective synthetic azapeptide CD36 ligand MPE-298 have been revealed. After binding to CD36, MPE-298 was rapidly internalized by and simultaneously induced CD36 endocytosis through activation of the Lyn and Syk (spleen) tyrosine kinases. Within this internalized complex, MPE-298 inhibited oxLDL/LOX-1-induced chemokine ligand 2 (CCL2) secretion, abolished the production of mtROS, and prevented mitochondrial membrane potential depolarization in macrophages. This occurred through the inhibition of the multiple-component enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) by oxLDL-activated LOX-1, which was further supported by the reduced recruitment of the p47phox subunit and small GTPase (Rac) 1/2/3 into the plasma membrane. A new mechanism for alleviating oxLDL-induced oxidative stress and inflammation in macrophages is highlighted using the CD36 ligand MPE-298.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".