p300-mediated histone H3K18 lactylation promotes mitochondrial ROS accumulation via mitophagy inhibition to potentiate dopamine agonists efficacy in prolactinomas - PubMed
6 hours ago
- #ROS
- #Mitophagy
- #Prolactinoma
- Prolactinomas are common functional pituitary adenomas, with dopamine agonists (DAs) as first-line therapy, but 10-30% of patients develop resistance.
- Reduced p300 expression was observed in DA-resistant tumors, inversely correlating with DA dosage.
- DAs decrease p300 by suppressing the cAMP/PKA/CREB pathway.
- Augmenting p300 enhances DA-induced antitumor effects, linked to elevated histone H3K18 lactylation (H3K18la).
- p300-dependent H3K18la upregulates Ndufs7 and Washc1, leading to mitochondrial ROS accumulation and impaired mitophagy.
- YF-2, a p300 activator, synergizes with DAs to inhibit tumor growth in MMQ and AtT-20 cells.
- The study identifies a p300-H3K18la-NDUFS7/WASH1 axis linking mitophagy inhibition to ROS accumulation, suggesting p300 targeting to improve DA efficacy.