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Ketamine inhibits T...
Ketamine inhibits TNF-α-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS
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- Deng, Bin (författare)
- Xiamen University,Xi'an Jiaotong University
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- Yang, Daowei (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Other operations, LTH,Faculty of Engineering, LTH,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Wu, Huanghui (författare)
- Xiamen University
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- Wang, Lu (författare)
- Xiamen University,Jiaxing University
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- Wu, Rui (författare)
- Xiamen University
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- Zhu, Hongrui (författare)
- Xiamen University
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- Huang, Ailing (författare)
- Xiamen University
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- Song, Jingyi (författare)
- Xiamen University
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- Cai, Tieliang (författare)
- Xiamen University
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- Liu, Shanshan (författare)
- Xiamen University
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- Wu, Jingsi (författare)
- Xiamen University
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- Zhou, Huiying (författare)
- Xiamen University
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- Li, Chunhui (författare)
- Xiamen University
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(creator_code:org_t)
- 2022-02-19
- 2022
- Engelska.
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Ingår i: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 8:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Systemic inflammatory response syndrome (SIRS) is a sepsis-associated inflammatory state and a self-defense mechanism against specific and nonspecific stimuli. Ketamine influences many key processes that are altered during sepsis. However, the underlying mechanisms remain incompletely understood. In this study, TNF-α-treated mice, as well as HT-29 and L929 cell models, were applied to characterize TNF-α-induced systemic and local cecal tissue inflammatory responses. Behavioral, biochemical, histological, and molecular biological approaches were applied to illustrate the related processes. Mice with TNF-α-induced SIRS showed systemic and local cecal tissue inflammatory responses, as indicated by increased levels of high mobility group box 1 protein (HMGB1), chemokines (C-X-C motif) ligand 10 (CXCL10), interleukin-6 (IL-6), and IL-10, as well as high mortality. Ketamine pretreatment alleviated death rates, symptoms, and the production of inflammatory cytokines induced by TNF-α in mice. Moreover, ketamine also protected the mice from TNF-α-induced cecal damage by suppressing the phosphorylation of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). In addition, our results showed that ketamine efficiently inhibited TNF-α-induced necroptosis in HT-29 and L929 cells. Furthermore, we explored the mechanism using different L929 cell lines. The results displayed that ketamine inhibited TNF-α-induced necroptosis by enhancing RIP1 ubiquitination and reducing the RIP1-RIP3 and RIP3-MLKL interactions, as well as the formation of necrosomes. Thus, our study may provide a new theoretical and experimental basis for treating diseases characterized by SIRS-associated inflammatory factor storms. Moreover, our exploration may provide potential molecular mechanisms and targets for therapeutic intervention and clinical application of ketamine.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Deng, Bin
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Yang, Daowei
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Wu, Huanghui
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Wang, Lu
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Wu, Rui
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Zhu, Hongrui
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visa fler...
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Huang, Ailing
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Song, Jingyi
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Cai, Tieliang
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Liu, Shanshan
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Wu, Jingsi
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Zhou, Huiying
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Li, Chunhui
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kirurgi
- Artiklar i publikationen
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Cell death disco ...
- Av lärosätet
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Lunds universitet