Hemin-induced transient senescence via DNA damage response: a neuroprotective mechanism against ferroptosis in intracerebral hemorrhage.

ABSTRACT: Intracerebral hemorrhage (ICH) poses acute fatality and long-term neurological risks, in part due to hemin and iron accumulation from hemoglobin breakdown. We observed that hemin induces DNA double-strand breaks (DSBs), prompting a senescence-like phenotype in neurons, necessitating a deeper exploration of cellular responses. Using experimental ICH models and human ICH patient tissue, we elucidate hemin-mediated DNA damage response (DDR) inducing transient senescence and delayed expression of heme oxygenase (HO-1). HO-1 co-localizes with senescence-associated β-Galactosidase (SA-β-Gal) in ICH patient tissues, emphasizing the clinical relevance of inducible HO-1 expression in senescent cells. We reveal a reversible senescence state protective against acute cell death by hemin, while repeat

SUBMITTER: Malojirao VH 

PROVIDER: S-EPMC12006456 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature