Reduced levels of A20 protein prompted RIPK1-dependent apoptosis and blood-brain barrier breakdown during cerebral ischemia reperfusion injury

Blood-brain barrier (BBB) leakage is an important cause of the exacerbation of pathological features of cerebral ischemia reperfusion injury (CIRI). However, the specific mechanism of BBB leakage is not clear. It was found that the CIRI resulted in RIPK1 activation and subsequent RIPK1-dependent apo...

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Bibliographic Details
Published in:PloS one 2023-08, Vol.18 (8), p.e0290015-e0290015
Main Authors: Yang, Chaonan, Wang, Yongjiao, Wu, Xiaohui, Gong, Min, Li, Ying
Format: Article
Language:English
Subjects:
A20 protein
Antibodies
Apoptosis
Autophagy
Biology and Life Sciences
Blood-brain barrier
Blood-Brain Barrier - metabolism
Brain
Brain damage
Brain injury
Brain Ischemia
Brain research
Breakdown
Carotid arteries
Cell death
Cerebral ischemia
Development and progression
Edema
Engineering and Technology
Health aspects
Homeostasis
Humans
Injuries
Ischemia
Kinases
Leakage
Medicine and Health Sciences
Methods
Nervous system
Permeability
Physiology
Proteins
Proteomics
Receptor-Interacting Protein Serine-Threonine Kinases - metabolism
Reperfusion
Reperfusion injury
Reperfusion Injury - pathology
Research and Analysis Methods
Tumor necrosis factor-TNF
Vectors (Biology)
Veins & arteries
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Summary:Blood-brain barrier (BBB) leakage is an important cause of the exacerbation of pathological features of cerebral ischemia reperfusion injury (CIRI). However, the specific mechanism of BBB leakage is not clear. It was found that the CIRI resulted in RIPK1 activation and subsequent RIPK1-dependent apoptosis (RDA). Inhibition of RIPK1 significantly reduced BBB breakdown and brain damage. The aim of this study is to investigate the mechanism of RIPK1 in the BBB leakage during CIRI. It was discovered by proteomics that autophagy activation resulting from ischemia and reperfusion significantly downregulated the level of A20 protein. A20 is an important protein that regulates RIPK1 and RDA. It was hypothesized that activation of autophagy caused by ischemic reperfusion led to a decrease in A20 protein, which, in turn, caused the activation of RIPK1 and the occurrence of RDA, leading to leakage of the BBB. The findings in this study revealed the role of RIPK1 in the cell death and BBB leakage upon cerebral ischemia reperfusion injury, and these findings provide a novel perspective for the treatment of ischemic reperfusion.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0290015