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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 ISSN 2045-2322.

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Official URL: https://doi.org/10.1038/s41598-021-04517-9

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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
Subjects: Q Science > QH Natural history
Q Science > QM Human anatomy
Q Science > QP Physiology
R Medicine > RC Internal medicine
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
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:
DateEvent
11 January 2022Published
23 December 2021Accepted
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 (Creative Commons)
Date of first compliant deposit: 17 February 2022
Date of first compliant Open Access: 22 February 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDInterdisziplinäres Zentrum für Klinische Forschung (Erlangen)http://viaf.org/viaf/155825489
03Z22JN12 Centre for Innovation Competence (ZIK) Septomics https://www.septomics.de/en/
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