scholarly journals Effective protection of rabbits’ explosive brain injury through blocking gap junction communication

2013 ◽  
Vol 12 (4) ◽  
Author(s):  
Z Yong-Ming ◽  
L Jia-Chuan ◽  
Y Yan-Yan ◽  
S Wen-Jiang ◽  
T Hong ◽  
...  
Keyword(s):  
Brain Injury ◽  
Gap Junction ◽  
Effective Protection ◽  
Gap Junction Communication

Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome release

2018 ◽  
Vol 119 (1) ◽  
pp. 305-311 ◽  
Author(s):  
Wei Chen ◽  
Yijun Guo ◽  
Wenjin Yang ◽  
Lei Chen ◽  
Dabin Ren ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gap Junction ◽  
Connexin 43 ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Cx43 Expression ◽  
Term Potentiation ◽  
Junction Protein

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using Western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results imply that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release. NEW & NOTEWORTHY We have demonstrated in rat traumatic brain injury (TBI) models that both phosphorylated connexin 43 (p-Cx43) expression and exosome release were elevated in the hippocampus following TBI. The promoted exosome release depends on the phosphorylation of Cx43 and requires ERK signaling activation. Exosome treatment could partially restore the attenuated long-term potentiation. Our results provide new insight for future therapeutic direction on the functional recovery of TBI by promoting p-Cx43-dependent exosome release but limiting the gap junction-mediated bystander effect.

scholarly journals Role of Gap Junction Protein Connexin43 in Astrogliosis Induced by Brain Injury

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47311 ◽  
Author(s):  
Nicolas Theodoric ◽  
John F. Bechberger ◽  
Christian C. Naus ◽  
Wun-Chey Sin
Keyword(s):  
Brain Injury ◽  
Gap Junction ◽  
Junction Protein ◽  
Gap Junction Protein

scholarly journals A Cell-Based High-Throughput Assay for Gap Junction Communication Suitable for Assessing Connexin 43–Ezrin Interaction Disruptors Using IncuCyte ZOOM

2016 ◽  
Vol 22 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Aleksandra R. Dukic ◽  
David W. McClymont ◽  
Kjetil Taskén
Keyword(s):  
Gap Junction ◽  
High Throughput ◽  
Connexin 43 ◽  
General Mechanism ◽  
Protein Protein Interaction ◽  
Gap Junction Communication ◽  
Anchoring Protein ◽  
A Cell ◽  
Rat Liver Epithelial Cells ◽  
High Throughput Assay

Connexin 43 (Cx43), the predominant gap junction (GJ) protein, directly interacts with the A-kinase-anchoring protein (AKAP) Ezrin in human cytotrophoblasts and a rat liver epithelial cells (IAR20). The Cx43-Ezrin–protein kinase (PKA) complex facilitates Cx43 phosphorylation by PKA, which triggers GJ opening in cytotrophoblasts and IAR20 cells and may be a general mechanism regulating GJ intercellular communication (GJIC). Considering the importance of Cx43 GJs in health and disease, they are considered potential pharmaceutical targets. The Cx43-Ezrin interaction is a protein-protein interaction that opens possibilities for targeting with peptides and small molecules. For this reason, we developed a high-throughput cell-based assay in which GJIC can be assessed and new compounds characterized. We used two pools of IAR20 cells, calcein loaded and unloaded, that were mixed and allowed to attach. Next, GJIC was monitored over time using automated imaging via the IncuCyte imager. The assay was validated using known GJ inhibitors and anchoring peptide disruptors, and we further tested new peptides that interfered with the Cx43-Ezrin binding region and reduced GJIC. Although an AlphaScreen assay can be used to screen for Cx43-Ezrin interaction inhibitors, the cell-based assay described is an ideal secondary screen for promising small-molecule hits to help identify the most potent compounds.

scholarly journals Propagation Distance of the α-Particle-Induced Bystander Effect: The Role of Nuclear Traversal and Gap Junction Communication

2009 ◽  
Vol 171 (5) ◽  
pp. 513-520 ◽  
Author(s):  
Sylvain Gaillard ◽  
David Pusset ◽  
Sonia M. de Toledo ◽  
Michel Fromm ◽  
Edouard I. Azzam
Keyword(s):  
Gap Junction ◽  
Bystander Effect ◽  
Propagation Distance ◽  
Gap Junction Communication

General Anesthetics Inhibit Gap Junction Communication in Cultured Organotypic Hippocampal Slices

2006 ◽  
Vol 102 (6) ◽  
pp. 1692-1698 ◽  
Author(s):  
Kirsten Wentlandt ◽  
Marina Samoilova ◽  
Peter L. Carlen ◽  
Hossam El Beheiry
Keyword(s):  
Gap Junction ◽  
Hippocampal Slices ◽  
General Anesthetics ◽  
Gap Junction Communication

Inhibiting N-cadherin-mediated adhesion affects gap junction communication in isolated rat hearts

2010 ◽  
Vol 30 (3) ◽  
pp. 193-200 ◽  
Author(s):  
Hongjun Zhu ◽  
Hegui Wang ◽  
Xiwen Zhang ◽  
Xiaofeng Hou ◽  
Kejiang Cao ◽  
...  
Keyword(s):  
Gap Junction ◽  
Gap Junction Communication ◽  
Rat Hearts ◽  
Isolated Rat
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