The globular domain of extracellular histones mediates cytotoxicity via membrane disruption mechanism.

ABSTRACT: Histones are traditionally recognized for structuring nuclear architecture and regulating gene expression. Recent advances have revealed their roles in inflammation, coagulation, and immune responses, where they act as damage-associated molecular patterns. The mechanisms by which histones induce membrane leakage are not well understood, and certain cells, including endothelial cells and peritoneal macrophages, show resistance to histone-mediated pore formation. We utilized liposome leakage assays to explore the pore-forming capabilities of different histone configurations, including individual histones, tail regions, and globular domains. Our results demonstrate that globular domains primarily drive pore formation. Using cytotoxicity assays, we further demonstrate that the globular domain

SUBMITTER: Pan Y 

PROVIDER: S-EPMC11732447 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature