Abstract P241: Irisin Protects Mitochondria Function During Pulmonary Ischemia Reperfusion Injury

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Chunyu Zeng ◽  
Ken Chen
Keyword(s):  
Protective Effect ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Alveolar Epithelium ◽  
Lung Edema ◽  
High Morbidity ◽  
Alveolar Wall ◽  
Atp Production

Background: Ischemia and reperfusion (I/R) induced lung injury is one of the most important and common causes of early and high morbidity and mortality. The mitochondrial damage of alveolar epithelium cells leads to further damage in lung I/R by augmented ROS activity and inflammation. Previous study show a humoral myokine, irisin, has been found stimulate mitochondrial biogenesis. We hypothesize irisin might protect lung from I/R injury. Methods: The lung I/R injury model was performed on C57BL/6J mice. The pulmonary protection of exogenous irisin was indicated by lung edema and function measurement, and the survival of mice. The localization of irisin was measured by immunohistochemistry and immunofluorescence staining. And the protective effect of irisin to mitochondrial was demonstrated by ATP production, ROS production, mitochondria-dependent apoptosis measurement, and so on. Results: There was no endogenous irisin expression in the alveolar wall in normal mice. However, it is interesting to find that, irisin was in the alveoli after lung I/R injury. The increased irisin in lung might be from plasma, because in the mean time, the plasma irisin levels were decreased. Exogenous intravenous injection of irisin protect the lung from I/R injury. The protective effect might be via the protection on the mitochondria in lung, exogenous irisin was found to localize in the mitochondria, the impaired mitochondrial function in I/R mice was reversed after irisin treatment. Moreover, there was colocalization between the irisin and UCP2, exogenous irisin decreased the I/R-induced UCP2 degradation. The role of UCP2 on the protection of mitochondria is further confirmed in the in in-vivo experiment, inhibition of UCP2 or knockout of UCP2 would make the protection of irisin on lung function and mitochondrial function lost. Conclusions: Administration with exogenous irisin would alleviate the I/R damage, reduced the inflammatory and superoxide factors, ameliorated the mitochondrial dysfunction, via the binding of irisin and UCP2 in lung.

scholarly journals VX765, a Specific Caspase-1 Inhibitor, Alleviates Lung Ischemia Reperfusion Injury by Suppressing Endothelial Pyroptosis and Barrier Dysfunction

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Siyi Wu ◽  
Zhao Li ◽  
Mengling Ye ◽  
Chunxia Liu ◽  
Hao Liu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
High Morbidity ◽  
Barrier Dysfunction ◽  
Caspase 1

Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process with high morbidity and mortality. An important pathophysiological characteristic of LIRI is endothelial barrier dysfunction, although the mechanism involved in this process remains unclear. VX765, a specific caspase-1 inhibitor, has been shown to have a protective effect against several diseases including sepsis, atherosclerosis, and glial inflammatory disease. The objective of this study was to determine whether VX765 had a protective effect in LIRI. The results showed that lung ischemia/reperfusion (I/R) and oxygen/glucose deprivation and reoxygenation (OGD/R) induced endothelial pyroptosis and barrier dysfunction characterized by an inflammatory response. Treatment with VX765 successfully alleviated I/R- and OGD/R-induced endothelial pyroptosis and barrier dysfunction by inhibiting caspase-1 in vivo and in vitro. In conclusion, these findings showed that VX765 provided effective protection against lung I/R-induced endothelial pyroptosis and barrier dysfunction.

scholarly journals TRAP1 Provides Protection Against Myocardial Ischemia-Reperfusion Injury by Ameliorating Mitochondrial Dysfunction

2015 ◽  
Vol 36 (5) ◽  
pp. 2072-2082 ◽  
Author(s):  
Peng Zhang ◽  
Yong Lu ◽  
Dong Yu ◽  
Dadong Zhang ◽  
Wei Hu
Keyword(s):  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Complex Activity ◽  
Atp Production

Background: Tumor necrosis factor receptor-associated protein 1 (TRAP1), an essential mitochondrial chaperone is induced in rat hearts following ischemia/reperfusion (I/R), but its role in myocardial I/R injury is unclear. The present study examined the function of TRAP1 in cardiomyocyte hypoxia/reoxygenation injury in vitro and myocardial I/R injury in vivo. Methods: HL-1 cardiomyocytes transfected with TRAP1 or vector were subjected to simulated I/R (SI/R) in vitro. Cell death and mitochondrial function were assessed. Wild type (WT) and TRAP1 knockout (TRAP1 KO) mice were subjected to cardiac I/R in vivo. The infarct size and myocardial apoptosis were determined. WT and TRAP1 KO cardiomyocytes were subjected to SI/R in vitro. Mitochondrial function was assessed. Results: TRAP1 overexpression protects HL-1 cardiomyocytes from SI/R-induced cell death in vitro. The reduced cell death was associated with decreased ROS generation, better-preserved mitochondrial ETC complex activity, membrane potential, and ATP production, as well as delayed mPTP opening. Loss of TRAP1 aggravates SI/R-induced mitochondrial damage in cardiomyocytes in vitro and myocardial I/R injury and apoptosis in vivo. Conclusion: The results of the present study show that TRAP1 provides cardioprotection against myocardial I/R by ameliorating mitochondrial dysfunction.

scholarly journals Effects and Mechanisms of Tea and Its Bioactive Compounds for the Prevention and Treatment of Cardiovascular Diseases: An Updated Review

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 166 ◽  
Author(s):  
Shi-Yu Cao ◽  
Cai-Ning Zhao ◽  
Ren-You Gan ◽  
Xiao-Yu Xu ◽  
Xin-Lin Wei ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Bioactive Compounds ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Blood Lipid ◽  
High Morbidity ◽  
Global Public Health

Cardiovascular diseases (CVDs) are critical global public health issues with high morbidity and mortality. Epidemiological studies have revealed that regular tea drinking is inversely associated with the risk of CVDs. Additionally, substantial in vitro and in vivo experimental studies have shown that tea and its bioactive compounds are effective in protecting against CVDs. The relevant mechanisms include reducing blood lipid, alleviating ischemia/reperfusion injury, inhibiting oxidative stress, enhancing endothelial function, attenuating inflammation, and protecting cardiomyocyte function. Moreover, some clinical trials also proved the protective role of tea against CVDs. In order to provide a better understanding of the relationship between tea and CVDs, this review summarizes the effects of tea and its bioactive compounds against CVDs and discusses potential mechanisms of action based on evidence from epidemiological, experimental, and clinical studies.

scholarly journals Gastrin Attenuates Renal Ischemia/Reperfusion Injury by a PI3K/Akt/Bad-Mediated Anti-apoptosis Signaling

2020 ◽  
Vol 11 ◽  
Author(s):  
Chao Liu ◽  
Ken Chen ◽  
Huaixiang Wang ◽  
Ye Zhang ◽  
Xudong Duan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Periodic Acid ◽  
Drug Candidate ◽  
Gastrointestinal Hormone ◽  
Akt Inhibitor ◽  
Periodic Acid Schiff

Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Gastrin, a gastrointestinal hormone, is involved in the regulation of kidney function of sodium excretion. However, whether gastrin has an effect on kidney I/R injury is unknown. Here we show that cholecystokinin B receptor (CCKBR), the gastrin receptor, was significantly up-regulated in I/R-injured mouse kidneys. While pre-administration of gastrin ameliorated I/R-induced renal pathological damage, as reflected by the levels of serum creatinine and blood urea nitrogen, hematoxylin and eosin staining and periodic acid-Schiff staining. The protective effect could be ascribed to the reduced apoptosis for gastrin reduced tubular cell apoptosis both in vivo and in vitro. In vitro studies also showed gastrin preserved the viability of hypoxia/reoxygenation (H/R)-treated human kidney 2 (HK-2) cells and reduced the lactate dehydrogenase release, which were blocked by CI-988, a specific CCKBR antagonist. Mechanistically, the PI3K/Akt/Bad pathway participates in the pathological process, because gastrin treatment increased phosphorylation of PI3K, Akt and Bad. While in the presence of wortmannin (1 μM), a PI3K inhibitor, the gastrin-induced phosphorylation of Akt after H/R treatment was blocked. Additionally, wortmannin and Akt inhibitor VIII blocked the protective effect of gastrin on viability of HK-2 cells subjected to H/R treatment. These studies reveals that gastrin attenuates kidney I/R injury via a PI3K/Akt/Bad-mediated anti-apoptosis signaling. Thus, gastrin can be considered as a promising drug candidate to prevent AKI.

scholarly journals Monitoring of Lung Edema by Microwave Reflectometry during Lung Ischemia-Reperfusion Injury in vivo

2006 ◽  
Vol 38 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Kai Nowak ◽  
Michael Schaefer ◽  
Wolfgang Gross ◽  
Roman Patrick Metzger ◽  
Peter Hohenberger ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lung Edema

scholarly journals Involvement of GPR30 in protection effect of Dexmedetomidine against myocardial ischemia/reperfusion injury in rat via AKT pathway

2021 ◽  
Author(s):  
Zheming Shao ◽  
Qihong Shen ◽  
Min Kong ◽  
Huadong Ni ◽  
Xiaomin Hou
Keyword(s):  
Protective Effect ◽  
Molecular Mechanism ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Mechanism Analysis ◽  
Protective Effects ◽  
Akt Inhibitor

Acute myocardial infarction (AMI) is a heart disease that seriously threatens human health. Dexmedetomidine (DEX) has a certain protective effect on cardiac injury. This study investigated the cardioprotective effect of DEX and its potential molecular mechanism in vivo and in vitro. The results showed that DEX could significantly increase the viability of hypoxia/reoxygenation (H/R) treated cardiomyocytes and reduce oxidative damage and apoptosis. Further molecular mechanism analysis showed that the above cardiac protective effects may be related to Akt signaling pathway. In addition, the expression of G-Protein Receptor 30 (GPR30) was promoted after H/R treatment. However, knockdown of GPR30 by shRNA significantly counteracted the cardioprotective effect of DEX. Meanwhile, we constructed a rat model of AMI to investigate the role of GPR30 in vivo. The results showed that DEX significantly reduced the infarct size, and GPR30 agonist G1 enhanced the protective effect of DEX on heart. On the contrary, protein kinase B (AKT) inhibitor LY294002 counteracted the protective effect of DEX on heart, suggesting that GPR30 enhanced the protective effect of DEX on ischemia-reperfusion induced heart injury by regulating AKT related pathways. In conclusion, our study provides a potential target for the clinical treatment of AMI.

scholarly journals Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI

2017 ◽  
Vol 29 (1) ◽  
pp. 194-206 ◽  
Author(s):  
Heather M. Perry ◽  
Liping Huang ◽  
Rebecca J. Wilson ◽  
Amandeep Bajwa ◽  
Hiromi Sesaki ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Kidney Injury ◽  
Related Protein

The proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective β-hydroxybutyrate signaling pathway. Loss of DRP1 preserved mitochondrial structure and reduced oxidative stress in injured kidneys. Lastly, proximal tubule deletion of DRP1 after ischemia-reperfusion injury attenuated progressive kidney injury and fibrosis. These results implicate DRP1 and mitochondrial dynamics as an important mediator of AKI and progression to fibrosis and suggest that DRP1 may serve as a therapeutic target for AKI.

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