scholarly journals Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats

2017 ◽  
Vol 122 (5) ◽  
pp. 1095-1105 ◽  
Author(s):  
Shuai Yang ◽  
Geoffrey W. Abbott ◽  
Wei Dong Gao ◽  
Jin Liu ◽  
Chaozhi Luo ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Glycogen Synthase Kinase ◽  
Ischemia And Reperfusion ◽  
Glycogen Synthase Kinase 3Β ◽  
Ischemia And Reperfusion Injury ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Dependent Cell ◽  
Gsk 3Β

Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway. NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury. However, it is unclear whether ischemic conditioning of visceral organs such as the liver, the largest metabolic organ in the body, can produce cardioprotection. This is the first study to show the cardioprotective effect of remote liver ischemic conditioning in a rat model of myocardial I/R injury. We also, for the first time, demonstrated these protective properties are associated with glycogen synthase kinase-3β-dependent cell-survival signaling pathway.

Inhibition of Glycogen Synthase Kinase-3β Attenuates Organ Injury and Dysfunction Associated With Liver Ischemia-Reperfusion and Thermal Injury in the Rat

Shock ◽  
2015 ◽  
Vol 43 (4) ◽  
pp. 369-378 ◽  
Author(s):  
Joao Rocha ◽  
Maria-Eduardo Figueira ◽  
Andreia Barateiro ◽  
Adelaide Fernandes ◽  
Dora Brites ◽  
...  
Keyword(s):  
Thermal Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Glycogen Synthase Kinase ◽  
Organ Injury ◽  
Liver Ischemia ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Dextromethorphan Attenuates NADPH Oxidase-Regulated Glycogen Synthase Kinase 3β and NF-κB Activation and Reduces Nitric Oxide Production in Group A Streptococcal Infection

2018 ◽  
Vol 62 (6) ◽  
pp. e02045-17 ◽  
Author(s):  
Chia-Ling Chen ◽  
Miao-Huei Cheng ◽  
Chih-Feng Kuo ◽  
Yi-Lin Cheng ◽  
Ming-Han Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Streptococcal Toxic Shock Syndrome ◽  
Glycogen Synthase Kinase 3Β ◽  
Diphenylene Iodonium ◽  
Group A ◽  
Gsk 3Β

ABSTRACTGroup AStreptococcus(GAS) is an important human pathogen that causes a wide spectrum of diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), an antitussive drug, has been demonstrated to efficiently reduce inflammatory responses, thereby contributing to an increased survival rate of GAS-infected mice. However, the anti-inflammatory mechanisms underlying DM treatment in GAS infection remain unclear. DM is known to exert neuroprotective effects through an NADPH oxidase-dependent regulated process. In the present study, membrane translocation of NADPH oxidase subunit p47phoxand subsequent reactive oxygen species (ROS) generation induced by GAS infection were significantly inhibited via DM treatment in RAW264.7 murine macrophage cells. Further determination of proinflammatory mediators revealed that DM effectively suppressed inducible nitric oxide synthase (iNOS) expression and NO, tumor necrosis factor alpha, and interleukin-6 generation in GAS-infected RAW264.7 cells as well as in air-pouch-infiltrating cells from GAS/DM-treated mice. GAS infection caused AKT dephosphorylation, glycogen synthase kinase-3β (GSK-3β) activation, and subsequent NF-κB nuclear translocation, which were also markedly inhibited by treatment with DM and an NADPH oxidase inhibitor, diphenylene iodonium. These results suggest that DM attenuates GAS infection-induced overactive inflammation by inhibiting NADPH oxidase-mediated ROS production that leads to downregulation of the GSK-3β/NF-κB/NO signaling pathway.

scholarly journals Glycogen Synthase Kinase 3β Promotes Postoperative Cognitive Dysfunction by Inducing the M1 Polarization and Migration of Microglia

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jingjin Li ◽  
Chonglong Shi ◽  
Zhengnian Ding ◽  
Wenjie Jin
Keyword(s):  
Cognitive Dysfunction ◽  
Lithium Chloride ◽  
Glycogen Synthase ◽  
Postoperative Cognitive Dysfunction ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Central Nervous System Complication ◽  
Proinflammatory Mediators ◽  
M1 Polarization ◽  
Gsk 3Β

Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system complication, especially in the elderly. It has been consistently reported that the pathological process of this clinical syndrome is related to neuroinflammation and microglial proliferation. Glycogen synthase kinase 3β (GSK-3β) is a widely expressed kinase with distinct functions in different types of cells. The role of GSK-3β in regulating innate immune activation has been well documented, but as far as we know, its role in POCD has not been fully elucidated. Lithium chloride (LiCl) is a widely used inhibitor of GSK-3β, and it is also the main drug for the treatment of bipolar disorder. Prophylactic administration of lithium chloride (2 mM/kg) can inhibit the expression of proinflammatory mediators in the hippocampus, reduce the hippocampal expression of NF-κB, and increase both the downregulation of M1 microglial-related genes (inducible nitric oxide synthase and CD86) and upregulation of M2 microglial-related genes (IL-10 and CD206), to alleviate the cognitive impairment caused by orthopedic surgery. In vitro, LiCl reversed LPS-induced production of proinflammatory mediators and M1 polarization of microglia. To sum up these results, GSK-3β is a key contributor to POCD and a potential target of neuroprotective strategies.

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