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Metzing, Uta Barbara; von Loeffelholz, Christian; Steidl, Ricardo; Romeike, Bernd; Winkler, René; Rauchfuß, Falk; Settmacher, Utz; Stoppe, Christian; Coldewey, Sina M.; Weinmann, Claudia; Weickert, Martin O.; Claus, Ralf A.; Birkenfeld, Andreas L.; Kosan, Christian; Horn, Paul

Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis

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  • Medientyp: E-Artikel
  • Titel: Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis
  • Beteiligte: Metzing, Uta Barbara; von Loeffelholz, Christian; Steidl, Ricardo; Romeike, Bernd; Winkler, René; Rauchfuß, Falk; Settmacher, Utz; Stoppe, Christian; Coldewey, Sina M.; Weinmann, Claudia; Weickert, Martin O.; Claus, Ralf A.; Birkenfeld, Andreas L.; Kosan, Christian; Horn, Paul
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Scientific Reports
  • Sprache: Englisch
  • DOI: 10.1038/s41598-021-04517-9
  • ISSN: 2045-2322
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle of human patients with peritoneal sepsis and a sepsis model of C57BL/6J mice. Patients undergoing open surgery were included in a cross-sectional study and blood and skeletal muscle samples were taken. Key markers of the UPR and cluster of differentiation 68 (CD68) as surrogate of inflammatory injury were evaluated by real-time PCR and histochemical staining. CD68 mRNA increased with sepsis in skeletal muscle of patients and animals (<jats:italic>p</jats:italic> &lt; 0.05). Mainly the inositol-requiring enzyme 1α branch of the UPR was upregulated as shown by elevated X-box binding-protein 1 (XBP1u) and its spliced isoform (XBP1s) mRNA (<jats:italic>p</jats:italic> &lt; 0.05, respectively). Increased expression of Gadd34 indicated activation of PRKR-Like Endoplasmic Reticulum Kinase (PERK) branch of the UPR, and was only observed in mice (<jats:italic>p</jats:italic> &lt; 0.001) but not human study subjects. Selected cell death signals were upregulated in human and murine muscle, demonstrated by increased bcl-2 associated X protein mRNA and TUNEL staining (<jats:italic>p</jats:italic> &lt; 0.05). In conclusion we provide a first characterization of the UPR in skeletal muscle in human sepsis.</jats:p>
  • Zugangsstatus: Freier Zugang