Inhibition of O-GlcNAcylation protects from Shiga toxin-mediated cell injury and lethality in hostopen access
- Authors
- Lee, Kyung-Soo; Lee, Jieun; Lee, Pureum; Jeon, Bong Chan; Song, Min Yeong; Kwak, Sojung; Lee, Jungwoon; Kim, Jun-Seob; Kim, Doo-Jin; Kim, Ji Hyung; Tesh, Vernon L.; Lee, Moo-Seung; Park, Sung-Kyun
- Issue Date
- Jan-2022
- Publisher
- WILEY
- Keywords
- apoptosis; hemolytic uremic syndrome; inflammation; O-GlcNAcylation; Shiga toxin
- Citation
- EMBO MOLECULAR MEDICINE, v.14, no.1
- Journal Title
- EMBO MOLECULAR MEDICINE
- Volume
- 14
- Number
- 1
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/84592
- DOI
- 10.15252/emmm.202114678
- ISSN
- 1757-4676
- Abstract
- Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life-threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O-GlcNAcylation, a type of post-translational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx-mediated increase in O-GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx-susceptible cells. The protective effect of O-GlcNAc inhibition for Stx-mediated pathogenic responses was also verified using three-dimensional (3D)-cultured spheroids or organoids mimicking the human kidney. Treatment with an O-GlcNAcylation inhibitor remarkably improved the major disease symptoms and survival rate for mice intraperitoneally injected with a lethal dose of Stx. In conclusion, this study elucidates O-GlcNAcylation-dependent pathogenic mechanisms of Stxs and demonstrates that inhibition of aberrant O-GlcNAcylation is a potential approach to treat Stx-mediated diseases.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - ETC > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/84592)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.