NPM3 functions as a lactyltransferase to promote necroptosis in male diabetic cardiomyopathy mice models via FASN transcription modulation - PubMed
3 days ago
- #Necroptosis
- #Diabetic Cardiomyopathy
- #Histone Lactylation
- NPM3 functions as a lactyltransferase promoting necroptosis in male diabetic cardiomyopathy (DCM) mice models.
- Lactate-mediated histone lactylation (H3K18la and H3K27la) modulates FASN transcription, contributing to DCM pathogenesis.
- NPM3 regulates H3K18la and H3K27la, activating FASN transcription and triggering necroptosis in DCM.
- Dihydroartemisinin (DHA) inhibits NPM3 lactyltransferase activity by competing for lactate binding sites, reducing necroptosis and cardiac damage.
- DHA treatment alleviates diastolic dysfunction and ventricular hypertrophy in DCM models by lowering NPM3, H3K18la, H3K27la, and FASN expression.
- Inhibiting NPM3-induced histone lactylation via DHA presents a potential therapeutic strategy for DCM.