H3K14 lactylation exacerbates neuronal ferroptosis by inhibiting calcium efflux following intracerebral hemorrhagic stroke.

ABSTRACT: Inhibiting neuronal ferroptosis is essential for mitigating neural damage and enhancing recovery in central nervous system (CNS) disorders, including intracerebral hemorrhagic stroke (ICH). Lactate accumulation correlates with ICH severity, yet the role of lactate-derived histone lactylation, a novel epigenetic modification, in ferroptosis and its mechanisms is not fully understood. In this study, we aimed to investigate the role of histone lactylation on neuronal ferroptosis in ICH models, both in vitro and in vivo. We discovered elevated lactate and histone lactylation post-ICH in mice, with a significant increase in H3K14la during the early stages of ferroptosis in hemin-challenged primary cortical neurons. Pharmacological or genetic inhibition of H3K14la by targeting lactate dehydrogen

SUBMITTER: Sun T 

PROVIDER: S-EPMC12287320 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature