Back to Search
Start Over
Protection by selective mTORC2 inhibition of Zymosan-induced hypotension and systemic inflammation mediated via IKKα/IκB-α/NF-κB activation.
- Source :
-
Prostaglandins & other lipid mediators [Prostaglandins Other Lipid Mediat] 2024 Dec; Vol. 175, pp. 106918. Date of Electronic Publication: 2024 Oct 24. - Publication Year :
- 2024
-
Abstract
- Non-septic shock is a serious condition leading to multiple organ dysfunction. Although targeting the mammalian target of the rapamycin complex 1 (mTORC1) signaling pathway exerts potent anti-inflammatory activity, little is known about mTORC2's contribution to non-septic shock. Thus, our research aims to investigate mTORC2's contribution and associated changes of IκB kinase (IKKα)/inhibitor κB (IκB-α)/nuclear factor-ĸB (NF-κB) pathway on Zymosan (ZYM)-induced non-septic rat model using the novel mTORC2 selective inhibitor JR-AB2-011. Rats were given saline (4 ml/kg), dimethylsulfoxide (DMSO) (4 ml/kg), ZYM (500 mg/kg), and (or) JR-AB2-011 (1 mg/kg). Mean arterial pressure (MAP) and heart rate (HR) of rats were recorded. JR-AB2-011 reversed both ZYM-induced reduction in MAP and increase in HR. Protein expression and/or phosphorylation of rictor, protein kinase B (Akt), IκB-α, IKKα, NF-κB p65, inducible nitric oxide synthase (iNOS), nitrotyrosine, cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, besides prostaglandin (PG) E <subscript>2</subscript> levels were measured. The enhanced expression of the proteins mentioned above has been inhibited by JR-AB2-011. These data suggest mTORC2's promising role in ZYM-induced hypotension and systemic inflammation mediated via IKKα/IκB-α/NF-κB pathway.<br /> (Copyright © 2024. Published by Elsevier Inc.)
- Subjects :
- Animals
Rats
Male
NF-KappaB Inhibitor alpha metabolism
Signal Transduction drug effects
Rats, Sprague-Dawley
Mechanistic Target of Rapamycin Complex 2 metabolism
Mechanistic Target of Rapamycin Complex 2 antagonists & inhibitors
Zymosan
NF-kappa B metabolism
I-kappa B Kinase metabolism
I-kappa B Kinase antagonists & inhibitors
Inflammation metabolism
Inflammation chemically induced
Inflammation drug therapy
Inflammation pathology
Hypotension chemically induced
Hypotension metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-8823
- Volume :
- 175
- Database :
- MEDLINE
- Journal :
- Prostaglandins & other lipid mediators
- Publication Type :
- Academic Journal
- Accession number :
- 39461547
- Full Text :
- https://doi.org/10.1016/j.prostaglandins.2024.106918