scholarly journals Cleavage of cyclic AMP-responsive element-binding protein H aggravates myocardial hypoxia reperfusion injury in a hepatocyte–myocardial cell co-culture system

2020 ◽  
Vol 48 (5) ◽  
pp. 030006052090483
Author(s):  
Zehao Jin ◽  
Ye Chen ◽  
Xiaochun Weng ◽  
Anwu Huang ◽  
Shuang Lin ◽  
...  

Objective This study aimed to determine whether proinflammatory cytokines have an effect on myocardial cells (MCs) and hepatocytes during myocardial ischemia to induce cyclic AMP-responsive element-binding protein H (CREBH) cleavage, activate the acute phase response in the liver, and cause a superimposed injury in MCs. Methods In this study, a hepatocyte–MC transwell co-culture system was used to investigate the relationship between myocardial hypoxia/reperfusion injury and CREBH cleavage. MCs and hepatocytes of neonatal rats were obtained from the ventricles and livers of Sprague–Dawley rats, respectively. MCs were inoculated into the lower chamber of transwell chambers for 12 hours under hypoxia. Levels of the endoplasmic reticulum stress protein glucose-regulated protein 78 in MCs, CREBH in hepatocytes, inflammatory factor (tumor necrosis factor-α and interleukin-6) levels, and cell viability were evaluated. The effect of CREBH knockdown was also studied using a CREBH-specific short hairpin RNA (Ad-CREBHi). Results We found that proinflammatory cytokines affect MCs and hepatocytes during myocardial ischemia to induce CREBH cleavage, activate the acute phase response in the liver, and cause superimposed injury in MCs. Conclusions Expression of CREBH aggravates myocardial injury during myocardial ischemia.

Author(s):  
Frans van Roy ◽  
Volker Nimmrich ◽  
Anton Bespalov ◽  
Achim Möller ◽  
Hiromitsu Hara ◽  
...  

1998 ◽  
Vol 6 (3) ◽  
pp. 1-7 ◽  
Author(s):  
Menahem Segal ◽  
Diane D. Murphy

Activation of cyclic AMP dependent kinase is believed to mediate slow onset, long-term potentiation (LTP) in central neurons. Cyclic- AMP activates a cascade of molecular events leading to phosphorylation of the nuclear cAMP responsive element binding protein (pCREB). Whereas a variety of stimuli lead to activation of CREB, the molecular processes downstream of CREB, which may be relevant to neuronal plasticity, are yet largely unknown. We have recently found that following exposure to estradiol, pCREB mediates the large increase in dendritic spine density in cultured rat hippocampal neurons. We now extend these observations to include other stimuli, such as bicuculline, that cause the formation of new dendritic spines. Such stimuli share with estradiol the same mechanism of action in that both require activity-dependent CREB phosphorylation. Our observations suggest that CREB phosphorylation is a necessary, but perhaps not sufficient, step in the process leading to the generation of new dendritic spines and perhaps to functional plasticity as well.


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