Blockade of PKCβ protects against remote organ injury induced by intestinal ischemia and reperfusion via a p66shc-mediated mitochondrial apoptotic pathway

APOPTOSIS ◽  
2014 ◽  
Vol 19 (9) ◽  
pp. 1342-1353 ◽  
Author(s):  
Guangzhi Wang ◽  
Zhao Chen ◽  
Feng Zhang ◽  
Huirong Jing ◽  
Wei Xu ◽  
...  
2021 ◽  
Vol 22 (18) ◽  
pp. 9911
Author(s):  
Hannah V. Hayes ◽  
Vivian Wolfe ◽  
Michael O’Connor ◽  
Nick C. Levinsky ◽  
Giovanna Piraino ◽  
...  

Mesenteric ischemia and reperfusion (I/R) injury can ensue from a variety of vascular diseases and represents a major cause of morbidity and mortality in intensive care units. It causes an inflammatory response associated with local gut dysfunction and remote organ injury. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of metabolic homeostasis. The catalytic α1 subunit is highly expressed in the intestine and vascular system. In loss-of-function studies, we investigated the biological role of AMPKα1 in affecting the gastrointestinal barrier function. Male knock-out (KO) mice with a systemic deficiency of AMPKα1 and wild-type (WT) mice were subjected to a 30 min occlusion of the superior mesenteric artery. Four hours after reperfusion, AMPKα1 KO mice exhibited exaggerated histological gut injury and impairment of intestinal permeability associated with marked tissue lipid peroxidation and a lower apical expression of the junction proteins occludin and E-cadherin when compared to WT mice. Lung injury with neutrophil sequestration was higher in AMPKα1 KO mice than WT mice and paralleled with higher plasma levels of syndecan-1, a biomarker of endothelial injury. Thus, the data demonstrate that AMPKα1 is an important requisite for epithelial and endothelial integrity and has a protective role in remote organ injury after acute ischemic events.


PLoS ONE ◽  
2008 ◽  
Vol 3 (4) ◽  
pp. e2026 ◽  
Author(s):  
Rongqian Wu ◽  
Weifeng Dong ◽  
Youxin Ji ◽  
Mian Zhou ◽  
Corrado P. Marini ◽  
...  

2002 ◽  
Vol 13 (3) ◽  
pp. 144-150
Author(s):  
Yuriko Matsuura ◽  
Kaoru Koike ◽  
Atsuko Tsujii ◽  
Saeed Samarghandian ◽  
Shigeki Kushimoto ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sen Hu ◽  
Ming-Hua Du ◽  
Hong-Min Luo ◽  
Huan Wang ◽  
Yi Lv ◽  
...  

This study investigated the protective effect and mechanism of electroacupuncture at ST36 points on the intestinal barrier dysfunction and remote organ injury after intestinal ischemia and reperfusion injury in rats. Rats were subjected to gut ischemia for 30 min, and then received electroacupuncture for 30 min with or without abdominal vagotomy or intraperitoneal administration of cholinergicα7 nicotinic acetylcholine receptor (α7nAChR) inhibitor. Then we compared its effects with electroacupuncture at nonchannel points, vagal nerve stimulation, or intraperitoneal administration of cholinergic agonist. Cytokine levels in plasma and tissue of intestine, lung, and liver were assessed 60 min after reperfusion. Intestinal barrier injury was detected by histology, gut injury score, the permeability to 4 kDa FITC-dextran, and changes in tight junction protein ZO-1 using immunofluorescence and Western blot. Electroacupuncture significantly lowered the levels of tumor necrosis factor-αand interleukin-8 in plasma and organ tissues, decreased intestinal permeability to FITC-dextran, and prevented changes in ZO-1 protein expression and localization. However, abdominal vagotomy or intraperitoneal administration of cholinergicα7nAChR inhibitor reversed these effects of electroacupuncture. These findings suggest that electroacupuncture attenuates the systemic inflammatory response through protection of intestinal barrier integrity after intestinal ischemia injury in the presence of an intact vagus nerve.


2000 ◽  
Vol 48 (1) ◽  
pp. 32 ◽  
Author(s):  
Constantinos Kyriakides ◽  
William G. Austen ◽  
Yong Wang ◽  
Joanne Favuzza ◽  
Francis D. Moore ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document