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
Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase
Show others and affiliations
2017 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 19, no 13, 2771-2781 p.Article in journal (Refereed) Published
Abstract [en]

Energetic nutrients are oxidized to sustain high intracellular NADPH/NADP(+) ratios. NADPH-dependent reduction of thioredoxin-1 (Trx1) disulfide and glutathione disulfide by thioredoxin reductase-1 (TrxR1) and glutathione reductase (Gsr), respectively, fuels antioxidant systems and deoxyribonucleotide synthesis. Mouse livers lacking both TrxR1 and Gsr sustain these essential activities using an NADPH-independent methionine-consuming pathway; however, it remains unclear how this reducing power is distributed. Here, we show that liver-specific co-disruption of the genes encoding Trx1, TrxR1, and Gsr (triplenull) causes dramatic hepatocyte hyperproliferation. Thus, even in the absence of Trx1, methionine-fueled glutathione production supports hepatocyte S phase deoxyribonucleotide production. Also, Trx1 in the absence of TrxR1 provides a survival advantage to cells under hyperglycemic stress, suggesting that glutathione, likely via glutaredoxins, can reduce Trx1 disulfide in vivo. In triple-null livers like in many cancers, deoxyribonucleotide synthesis places a critical yet relatively low-volume demand on these reductase systems, thereby favoring high hepatocyte turnover over sustained hepatocyte integrity.

Place, publisher, year, edition, pages
Cell Press , 2017. Vol. 19, no 13, 2771-2781 p.
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-137799DOI: 10.1016/j.celrep.2017.06.019ISI: 000404121600012PubMedID: 28658624OAI: oai:DiVA.org:umu-137799DiVA: diva2:1128640
Available from: 2017-07-27 Created: 2017-07-27 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

fulltext(13114 kB)6 downloads
File information
File name FULLTEXT01.pdfFile size 13114 kBChecksum SHA-512
a1bdd6677eb039a04bab82b41d421338bab4c95406fbbff5ff8d7482434d429b62c6ce3938474123793ab3a9d047292159117cd87b360576de1444e300bf73bf
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Gustafsson, Tomas N.
By organisation
Clinical Bacteriology
In the same journal
Cell reports
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 6 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: 256 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