A Single Radioprotective Dose of Prostaglandin E₂ Blocks Irradiation-Induced Apoptotic Signaling and Early Cycling of Hematopoietic Stem Cells.

ABSTRACT: Ionizing radiation exposure results in acute and delayed bone marrow suppression. Treatment of mice with 16,16-dimethyl prostaglandin E₂ (dmPGE₂) prior to lethal ionizing radiation (IR) facilitates survival, but the cellular and molecular mechanisms are unclear. In this study we show that dmPGE₂ attenuates loss and enhances recovery of bone marrow cellularity, corresponding to a less severe hematopoietic stem cell nadir, and significantly preserves long-term repopulation capacity and progenitor cell function. Mechanistically, dmPGE₂ suppressed hematopoietic stem cell (HSC) proliferation through 24 h post IR, which correlated with fewer DNA double-strand breaks and attenuation of apoptosis, mitochondrial compromise, oxidative stress, and senescenc

SUBMITTER: Patterson AM 

PROVIDER: S-EPMC7419738 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature