RCL glycosylation of serum corticosteroid-binding globulin: implications in cortisol delivery and septic shock
Files
(Published version)
Date
2025
Authors
Chernykh, A.
Sumer-Bayraktar, Z.
Lee, J.H.
Meyer, E.J.
Torpy, D.J.
Thaysen-Andersen, M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Glycobiology, 2025; 35(4):cwaf013-1-cwaf013-10
Statement of Responsibility
Anastasia Chernykh, Zeynep Sumer-Bayraktar, Jessica H. Lee, Emily J. Meyer, David J. Torpy, Morten Thaysen-Andersen
Conference Name
Abstract
Corticosteroid-binding globulin (CBG) is a serum glycoprotein that binds and delivers anti-inflammatory cortisol to inflammatory sites through neutrophil elastase-mediated proteolysis of an exposed reactive centre loop (RCL) on CBG. Timely and tissue-specific delivery of cortisol is critical to alleviate inflammation including in life-threatening septic shock conditions. Herein, we firstly summarise our recently published report of functional RCL O- and N-glycosylation events of serum CBG (Chernykh, J Biol Chem, 2023). A key finding of that published work was the LC–MS/MS-based discovery of RCL O-glycans at Thr342 and Thr345 of serum CBG and their inhibitory roles in neutrophil elastase-mediated RCL proteolysis. While these observations are of significance as they implicate RCL O-glycosylation as a potential regulator of cortisol delivery, the link to septic shock remains unexplored. To this end, we used a similar LC–MS/MS approach to profile the RCL O-glycosylation of CBG purified from serum of twelve septic shock patients. Serum CBG from all patients exhibited RCL O-glycosylation comprising (di)sialyl T (NeuAc₁-₂Gal₁GalNAc₁) core 1-type O-glycan structures decorating exclusively the Thr342 site. Importantly, relative to less severe cases, individuals presenting with the most severe illness displayed elevated RCL O-glycosylation upon ICU admission, suggesting a previously unknown link to septic shock severity. Overall, we have elucidated the coordinated RCL N- and O-glycosylation events of serum CBG, which improve our understanding of molecular mechanisms governing the timely and tissue-specific delivery of cortisol to inflammatory sites. This work provides clues to molecular aberrations and disease mechanisms underpinning septic shock.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
©The Author(s) 2025. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com