scholarly journals MicroRNA-93 inhibits inflammatory responses and cell apoptosis after cerebral ischemia reperfusion by targeting interleukin-1 receptor-associated kinase 4

2017 ◽  
Vol 14 (4) ◽  
pp. 2903-2910 ◽  
Author(s):  
Feng Tian ◽  
Chao Yuan ◽  
Lixun Hu ◽  
Shihai Shan
Keyword(s):  
Cerebral Ischemia ◽  
Cell Apoptosis ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Cerebral Ischemia Reperfusion

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

Abstract 2473: Ubiquitin Ligase Huwe1 Modulates Prongf/p75ntr In Monkey Cerebral Ischemia-reperfusion Injury

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Qian G He ◽  
Lihua Yu ◽  
Wenming Xu ◽  
Jiachuan Duan ◽  
Jian Guo ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ubiquitin Ligase ◽  
Cell Apoptosis ◽  
Sham Group ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Model Group ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Background: Ischemic neuronal cell apoptosis is a principal neuropathological feature of stroke. The p75 neurotrophin receptor (p75NTR) induces apoptosis associated with JNK-p53-BAX pathway, p53 is the substrate of the HECT domain-containing E3 ubiquitin ligase Huwe1. Recent studies suggest that the precursor form of NGF (proNGF) binds to p75NTR, and withhold the interaction of proNGF/p75NTR is efficacious in reducing neuronal apoptosis. Studies on tumor and phylogeny, show that Huwe1 highly expressed in CNS, playing a role in the regulation of cell apoptosis and a variety of injury types. Our aim is to examine whether Huwe1 modulates proNGF/p75NTR in cerebral ischemia-reperfusion injury. Methods: Eight male rhesus monkey were randomly divided into two groups: sham(n=2) and model group(n=6). The model group was administered equal volume of PBS, or silencing huwe1 Lentiviral Vector or empty Vector in right caudatum and putamen using brain stereotaxic technology and subjected to transient right middle cerebral artery occlusion (MCAO) a month later. A battery of neurological evaluation and magnetic resonance imaging (MRI) were employed to evaluate animals. Animals were sacrificed 3 days after MCAO and brains were processed for testing transfection efficiency using GFP fluorescence and evaluating cell apoptosis using TUNEL staining. The related factors in caudatum, putamen, temporal lobe and hippocampus was analyzed with QPCR, western blotting with loading control GADPH, and Immunohistochemistry. Results: The model group showed significant functional deficit than sham group with neurological evaluation (p<0.05), whereas the silencing Huwe1 group’s was the most serious. In right caudatum and putament, ischemia-reperfusion injury increased the number of TUNEL+cells(p<0.05 vs sham group) and upregulation of huwe1, proNGF and p75NTR in protein and nucleotides level (p<0.05 vs sham group), but silencing Huwe1 group increased TUNEL+cells most significantly, produced profound modulation with decreased expression of Huwe1 and obvious upregulation of proNGF and p75NTR(p<0.05 vs PBS or empty Vector group) ( Figure 1 ). However, there is no significant difference in other positions (data not show). Conclusions: Huwe1 modulates proNGF/p75NTR in the cerebral ischemia-reperfusion injury, and p53 may be as a indirect fator involved in this process. Our findings provide a novel mechanism in regulating proNGF/p75NTR signaling, suggesting its potential therapeutic target in ischemic stroke.

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