Back to Search
Start Over
TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways
TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways
- Source :
- Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 1, Pp 1-16 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Neuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Programmed cell death
MAP Kinase Signaling System
Immunology
Perforation (oil well)
Apoptosis
Neuroprotection
Article
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
In vivo
Animals
Humans
Medicine
cardiovascular diseases
lcsh:QH573-671
Neurons
TNF Receptor-Associated Factor 3
lcsh:Cytology
business.industry
NF-kappa B
Neuro-vascular interactions
NF-κB
Cell Biology
Human brain
Middle Aged
Subarachnoid Hemorrhage
MAP Kinase Kinase Kinases
nervous system diseases
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
chemistry
Brain Injuries
Cancer research
Phosphorylation
business
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....ea2f3f508c4059e460b03519e4e26dd6
- Full Text :
- https://doi.org/10.1038/s41419-020-03278-z