liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1
Karolinska Institute, Sweden .
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Karolinska Institute, Sweden .
University of Dusseldorf, Germany .
Karolinska Institute, Sweden .
Show others and affiliations
2013 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 50, 20057-20062 p.Article in journal (Refereed) Published
Abstract [en]

Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione-disulfide oxidoreductase with a critical role for embryonic brain development. Here, we discovered an essential function of glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse studies based on two-photon microscopy revealed that morpholino-based knockdown of glutaredoxin 2 in zebrafish, a model organism to study vertebrate embryogenesis, resulted in a delayed and disordered blood vessel network. We were able to show that formation of a functional vascular system requires glutaredoxin 2-dependent reversible S-glutathionylation of the NAD(+)-dependent protein deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2-specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved between zebrafish and humans. These results link S-glutathionylation to vertebrate development and successful embryonic angiogenesis.

Place, publisher, year, edition, pages
National Academy of Sciences , 2013. Vol. 110, no 50, 20057-20062 p.
Keyword [en]
proteomics, cardiovascular system
National Category
Natural Sciences
URN: urn:nbn:se:liu:diva-102769DOI: 10.1073/pnas.1313753110ISI: 000328061700035OAI: diva2:683928

Funding Agencies|Karolinska Institutet|2379/07-225|Heinrich Heine University research commission of the Medical Faculty||Graduate School iBrain||CLICK imaging facility||KAW|2006.0192|Swedish Cancer Society|961|Swedish Research Council|K2012-68X-03529-41-3|

Available from: 2014-01-07 Created: 2013-12-26 Last updated: 2014-01-07

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Dahl Ejby Jensen, LasseCao, Yihai
By organisation
Division of Cardiovascular MedicineFaculty of Health Sciences
In the same journal
Proceedings of the National Academy of Sciences of the United States of America
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar
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

Altmetric score

Total: 102 hits
ReferencesLink to record
Permanent link

Direct link