| First Author | Hedblom A | Year | 2019 |
| Journal | Cell Death Dis | Volume | 10 |
| Issue | 2 | Pages | 72 |
| PubMed ID | 30683864 | Mgi Jnum | J:295515 |
| Mgi Id | MGI:6453907 | Doi | 10.1038/s41419-019-1342-6 |
| Citation | Hedblom A, et al. (2019) Heme detoxification by heme oxygenase-1 reinstates proliferative and immune balances upon genotoxic tissue injury. Cell Death Dis 10(2):72 |
| abstractText | Phenotypic changes of myeloid cells are critical to the regulation of premature aging, development of cancer, and responses to infection. Heme metabolism has a fundamental role in the regulation of myeloid cell function and activity. Here, we show that deletion of heme oxygenase-1 (HO-1), an enzyme that removes heme, results in an impaired DNA damage response (DDR), reduced cell proliferation, and increased cellular senescence. We detected increased levels of p16(INK4a), H2AXgamma, and senescence-associated-beta-galactosidase (SA-beta-Gal) in cells and tissues isolated from HO-1-deficient mice. Importantly, deficiency of HO-1 in residential macrophages in chimeric mice results in elevated DNA damage and senescence upon radiation-induced injury. Mechanistically, we found that mammalian target of rapamycin (mTOR)/S6 protein signaling is critical for heme and HO-1-regulated phenotype of macrophages. Collectively, our data indicate that HO-1, by detoxifying heme, blocks p16(INK4a) expression in macrophages, preventing DNA damage and cellular senescence. |
