umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Heme detoxification by heme oxygenase-1 reinstates proliferative and immune balances upon genotoxic tissue injury
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). 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.
Show others and affiliations
2019 (English)In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 10, article id 72Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 10, article id 72
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-156599DOI: 10.1038/s41419-019-1342-6ISI: 000457019800015PubMedID: 30683864OAI: oai:DiVA.org:umu-156599DiVA, id: diva2:1290433
Funder
Swedish Childhood Cancer FoundationSwedish Cancer SocietyAvailable from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved

Open Access in DiVA

fulltext(6234 kB)39 downloads
File information
File name FULLTEXT01.pdfFile size 6234 kBChecksum SHA-512
6d29c22f8c6f8aaffcc60825a7d88b0000b99954adec0fa6a32a838ab63ebfe5645180ed3939a0bbc5bcd1b27ea04c8baca0184af1d90b8f2914e8b4be9c0a07
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Persson, Jenny L.

Search in DiVA

By author/editor
Canesin, GiacomoPersson, Jenny L.
By organisation
Department of Molecular Biology (Faculty of Medicine)
In the same journal
Cell Death and Disease
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 39 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 135 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf