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Heme detoxification...
Heme detoxification by heme oxygenase-1 reinstates proliferative and immune balances upon genotoxic tissue injury
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- Hedblom, Andreas (författare)
- Umeå University,Lund University,Lunds universitet,Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Surgery, Cancer Research Institute and Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Translational Medicine, Lund University, Lund, Sweden,Experimentell cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Experimental Cancer Research, Malmö,Lund University Research Groups
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- Hejazi, Seyed M. (författare)
- Harvard University,Beth Israel Deaconess Medical Center
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- Canesin, Giacomo (författare)
- Harvard University,Beth Israel Deaconess Medical Center
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- Choudhury, Reeham (författare)
- Beth Israel Deaconess Medical Center,Harvard University
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- Hanafy, Khalid A. (författare)
- Harvard University
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- Csizmadia, Eva (författare)
- Harvard University,Beth Israel Deaconess Medical Center
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- Persson, Jenny L. (författare)
- Umeå University,Lund University,Lunds universitet,Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Translational Medicine, Lund University, Lund, Sweden,Experimentell cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Experimental Cancer Research, Malmö,Lund University Research Groups
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- Wegiel, Barbara (författare)
- Beth Israel Deaconess Medical Center,Harvard University
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(creator_code:org_t)
- 2019-01-25
- 2019
- Engelska.
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Ingår i: Cell Death and Disease. - : Nature Publishing Group. - 2041-4889. ; 10
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- 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 p16INK4a, H2AXγ, and senescence-associated-β-galactosidase (SA-β-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 p16INK4a expression in macrophages, preventing DNA damage and cellular senescence.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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