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Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis
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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 and Horn, Paul (2022) Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis. Scientific Reports, 12 (1). p. 504. doi:10.1038/s41598-021-04517-9
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WRAP-Endoplasmic-reticulum-stress-protein-skeleton-muscle-peritoneal-sepsis-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2707Kb) | Preview |
Official URL: https://doi.org/10.1038/s41598-021-04517-9
Abstract
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 (p < 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 (p < 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 (p < 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 (p < 0.05). In conclusion we provide a first characterization of the UPR in skeletal muscle in human sepsis.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Proteins -- Denaturation , Endoplasmic reticulum , Skeleton -- Muscles, Septicemia | |||||||||
| Journal or Publication Title: | Scientific Reports | |||||||||
| Publisher: | Nature Publishing Group UK | |||||||||
| ISSN: | 2045-2322 | |||||||||
| Official Date: | 11 January 2022 | |||||||||
| Dates: |
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| Volume: | 12 | |||||||||
| Number: | 1 | |||||||||
| Page Range: | p. 504 | |||||||||
| DOI: | 10.1038/s41598-021-04517-9 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Reuse Statement (publisher, data, author rights): | ** From Springer Nature via Jisc Publications Router ** History: received 16-09-2021; accepted 23-12-2021; registration 24-12-2021; pub-electronic 11-01-2022; online 11-01-2022; collection 12-2022. ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ | |||||||||
| Access rights to Published version: | Open Access | |||||||||
| RIOXX Funder/Project Grant: |
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