scholarly journals Protective role of ischemic conditioning procedures against skeletal muscle ischemia-reperfusion injury via improving in vivo energy metabolism and mitochondrial function

2017 ◽  
Vol 9 (2) ◽  
pp. 188
Author(s):  
A. Delgove ◽  
D. Detaille ◽  
J. Retortillo Garcia ◽  
J. Magat ◽  
V. Loyer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Ischemic Conditioning ◽  
Muscle Ischemia

scholarly journals cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING

2018 ◽  
Vol 314 (6) ◽  
pp. G655-G667 ◽  
Author(s):  
Zhao Lei ◽  
Meihong Deng ◽  
Zhongjie Yi ◽  
Qian Sun ◽  
Richard A. Shapiro ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Protective Role ◽  
Guanosine Monophosphate ◽  
Independent Manner

Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS−/−), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found cGAS−/− mice had significantly increased liver injury compared with WT or STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING. Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to anoxia/reoxygenation (A/R). We confirmed a previously published finding that hepatocytes do not express STING under normoxic conditions or after A/R. Hepatocytes and liver from cGAS−/− mice had increased cell death and reduced induction of autophagy under hypoxic conditions as well as increased apoptosis. Protection could be restored in cGAS−/− hepatocytes by overexpression of cGAS or by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a novel protective role for cGAS in the regulation of autophagy during liver I/R injury that occurs independently of STING. NEW & NOTEWORTHY Our studies are the first to document the important role of cGAS in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that cGAS protects liver from I/R injury in a STING-independent manner.

Therapeutic Metabolic Inhibition: Hydrogen Sulfide Significantly Mitigates Skeletal Muscle Ischemia Reperfusion Injury In Vitro and In Vivo

2010 ◽  
Vol 126 (6) ◽  
pp. 1890-1898 ◽  
Author(s):  
Peter W. Henderson ◽  
Sunil P. Singh ◽  
Andrew L. Weinstein ◽  
Vijay Nagineni ◽  
Daniel C. Rafii ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Metabolic Inhibition ◽  
Muscle Ischemia

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.

Cardioprotective role of endogenous hydrogen peroxide during ischemia-reperfusion injury in canine coronary microcirculation in vivo

2006 ◽  
Vol 291 (3) ◽  
pp. H1138-H1146 ◽  
Author(s):  
Toyotaka Yada ◽  
Hiroaki Shimokawa ◽  
Osamu Hiramatsu ◽  
Yoshisuke Haruna ◽  
Yoshitaka Morita ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
No Production ◽  
Coronary Vasodilatation ◽  
Before And After ◽  
Nos Inhibitor

We have recently demonstrated that endogenous H2O2 plays an important role in coronary autoregulation in vivo. However, the role of H2O2 during coronary ischemia-reperfusion (I/R) injury remains to be examined. In this study, we examined whether endogenous H2O2 also plays a protective role in coronary I/R injury in dogs in vivo. Canine subepicardial small coronary arteries (≥100 μm) and arterioles (<100 μm) were continuously observed by an intravital microscope during coronary I/R (90/60 min) under cyclooxygenase blockade ( n = 50). Coronary vascular responses to endothelium-dependent vasodilators (ACh) were examined before and after I/R under the following seven conditions: control, nitric oxide (NO) synthase (NOS) inhibitor NG-monomethyl-l-arginine (l-NMMA), catalase (a decomposer of H2O2), 8-sulfophenyltheophylline (8-SPT, an adenosine receptor blocker), l-NMMA + catalase, l-NMMA + tetraethylammonium (TEA, an inhibitor of large-conductance Ca2+-sensitive potassium channels), and l-NMMA + catalase + 8-SPT. Coronary I/R significantly impaired the coronary vasodilatation to ACh in both sized arteries (both P < 0.01); l-NMMA reduced the small arterial vasodilatation (both P < 0.01), whereas it increased ( P < 0.05) the ACh-induced coronary arteriolar vasodilatation associated with fluorescent H2O2 production after I/R. Catalase increased the small arterial vasodilatation ( P < 0.01) associated with fluorescent NO production and increased endothelial NOS expression, whereas it decreased the arteriolar response after I/R ( P < 0.01). l-NMMA + catalase, l-NMMA + TEA, or l-NMMA + catalase + 8-SPT further decreased the coronary vasodilatation in both sized arteries (both, P < 0.01). l-NMMA + catalase, l-NMMA + TEA, and l-NMMA + catalase + 8-SPT significantly increased myocardial infarct area compared with the other four groups (control, l-NMMA, catalase, and 8-SPT; all, P < 0.01). These results indicate that endogenous H2O2, in cooperation with NO, plays an important cardioprotective role in coronary I/R injury in vivo.

The role of glutamine in skeletal muscle ischemia/reperfusion injury in the rat hind limb model

1999 ◽  
Vol 178 (2) ◽  
pp. 147-150 ◽  
Author(s):  
Jeffrey T Prem ◽  
Michael Eppinger ◽  
Gary Lemmon ◽  
Sidney Miller ◽  
Dan Nolan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Hind Limb ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Muscle Ischemia

scholarly journals The role of neutrophil extracellular traps and TLR signaling in skeletal muscle ischemia reperfusion injury

2020 ◽  
Vol 34 (12) ◽  
pp. 15753-15770
Author(s):  
Nicole J. Edwards ◽  
Charles Hwang ◽  
Simone Marini ◽  
Chase A. Pagani ◽  
Philip J. Spreadborough ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Extracellular Traps ◽  
Tlr Signaling ◽  
Extracellular Traps ◽  
Muscle Ischemia
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