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Glutaredoxin regula...
Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1
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- Brautigam, Lars (författare)
- Karolinska Institutet
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- Dahl Ejby Jensen, Lasse (författare)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Karolinska Institute, Sweden
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- Poschmann, Gereon (författare)
- University of Dusseldorf, Germany
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- Nystrom, Staffan (författare)
- Karolinska Institutet
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- Bannenberg, Sarah (författare)
- Karolinska Institute, Sweden
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- Dreij, Kristian (författare)
- Karolinska Institutet
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- Lepka, Klaudia (författare)
- University of Dusseldorf, Germany
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- Prozorovski, Timour (författare)
- University of Dusseldorf, Germany
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- Montano, Sergio J (författare)
- Karolinska Institute, Sweden
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- Aktas, Orhan (författare)
- University of Dusseldorf, Germany
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- Uhlen, Per (författare)
- Karolinska Institutet
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- Stuehler, Kai (författare)
- University of Dusseldorf, Germany
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- Cao, Yihai (författare)
- Karolinska Institutet,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Karolinska Institute, Sweden
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- Holmgren, Arne (författare)
- Karolinska Institutet
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- Berndt, Carsten (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2013-11-25
- 2013
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:50, s. 20057-20062
- Relaterad länk:
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- proteomics
- cardiovascular system
- MATHEMATICS
- MATEMATIK
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Brautigam, Lars
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Dahl Ejby Jensen ...
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Poschmann, Gereo ...
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Nystrom, Staffan
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Bannenberg, Sara ...
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Dreij, Kristian
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visa fler...
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Lepka, Klaudia
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Prozorovski, Tim ...
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Montano, Sergio ...
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Aktas, Orhan
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Uhlen, Per
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Stuehler, Kai
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Cao, Yihai
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Holmgren, Arne
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Berndt, Carsten
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Medicinsk biotek ...
- Artiklar i publikationen
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Proceedings of t ...
- Av lärosätet
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Linköpings universitet
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Karolinska Institutet