Notch1–Nrf2 signaling crosstalk provides myocardial protection by reducing ROS formation

2020 ◽  
Vol 98 (2) ◽  
pp. 106-111
Author(s):  
Xue-liang Zhou ◽  
Xia Wu ◽  
Rong-rong Zhu ◽  
Hua Xu ◽  
Yun-yun Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathways ◽  
Myocardial Protection ◽  
Ischemia Reperfusion Injury ◽  
Antioxidant Activities ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Signaling Crosstalk ◽  
Neonate Rat

Both the Notch1 and Keap1–Nrf2 signaling pathways have cardioprotective effects, but the role of Notch1–Nrf2 crosstalk in myocardial ischemia–reperfusion injury is unclear. In this study, we established hypoxia–reoxygenation in neonate rat myocardial cells and employed γ-secretase inhibitor and curcumin to inhibit and activate the Notch1 and Keap1–Nrf2 signaling pathways, respectively. We found that the combined action of the Notch1 and Keap1–Nrf2 signaling pathways significantly increased cardiomyocyte viability, inhibited cardiomyocyte apoptosis, reduced the formation of reactive oxygen species, and increased antioxidant activities. In conclusion, these findings suggest that Notch1–Nrf2 crosstalk exerts myocardial protection by reducing the formation of reactive oxygen species.

scholarly journals Reactive Oxygen Species (ROS)-Activatable Prodrug for Selective Activation of ATF6 after Ischemia/Reperfusion Injury

2019 ◽  
Vol 11 (3) ◽  
pp. 292-297 ◽  
Author(s):  
Jonathan E. Palmer ◽  
Breanna M. Brietske ◽  
Tyler C. Bate ◽  
Erik A. Blackwood ◽  
Manasa Garg ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Selective Activation

scholarly journals Phospholipid oxidation products in ferroptotic myocardial cell death

2019 ◽  
Vol 317 (1) ◽  
pp. H156-H163 ◽  
Author(s):  
Aleksandra Stamenkovic ◽  
Grant N. Pierce ◽  
Amir Ravandi
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Myocardial Cell ◽  
Oxidation Products ◽  
Oxygen Species ◽  
New Therapeutic Approaches

Cell death is an important component of the pathophysiology of any disease. Myocardial disease is no exception. Understanding how and why cells die, particularly in the heart where cardiomyocyte regeneration is limited at best, becomes a critical area of study. Ferroptosis is a recently described form of nonapoptotic cell death. It is an iron-mediated form of cell death that occurs because of accumulation of lipid peroxidation products. Reactive oxygen species and iron-mediated phospholipid peroxidation is a hallmark of ferroptosis. To date, ferroptosis has been shown to be involved in cell death associated with Alzheimer’s disease, Huntington’s disease, cancer, Parkinson’s disease, and kidney degradation. Myocardial reperfusion injury is characterized by iron deposition as well as reactive oxygen species production. These conditions, therefore, favor the induction of ferroptosis. Currently there is no available treatment for reperfusion injury, which accounts for up to 50% of the final infarct size. This review will summarize the evidence that ferroptosis can induce cardiomyocyte death following reperfusion injury and the potential for this knowledge to open new therapeutic approaches for myocardial ischemia-reperfusion injury.

scholarly journals Probucol Reduces Testicular Torsion/Detorsion-Induced Ischemia/Reperfusion Injury in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Si-Ming Wei ◽  
Yu-Min Huang ◽  
Jian Zhou
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Expression ◽  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Treated Group ◽  
Myeloperoxidase Activity ◽  
Oxygen Species ◽  
Neutrophil Accumulation

This study investigated the effect of probucol, a potent antioxidant, on testicular torsion/detorsion-induced ischemia/reperfusion injury attributable to excess reactive oxygen species released by neutrophils. Sixty male Sprague-Dawley rats were randomly divided into sham-operated control, ischemia-reperfusion, and probucol-treated groups. In the ischemia-reperfusion group, testicular detorsion was performed after 2 hours of left testicular torsion. In the probucol-treated group, after performing the same surgical procedures as in the ischemia-reperfusion group, probucol was given intraperitoneally at testicular detorsion. Orchiectomy was performed to evaluate protein expression of E-selectin which is an endothelial cell adhesion molecule and mediates neutrophil adhesion to vascular endothelium, myeloperoxidase activity (a mark of neutrophil accumulation in the testis), malondialdehyde level (an indicator of reactive oxygen species), and spermatogenesis. E-selectin protein expression, myeloperoxidase activity, and malondialdehyde level were significantly increased, and testicular spermatogenesis was significantly decreased in the ipsilateral testes in the ischemia-reperfusion group, compared with the control group. The probucol-treated group showed significant decreases in E-selectin protein expression, myeloperoxidase activity, and malondialdehyde level and significant increase in testicular spermatogenesis in the ipsilateral testes, compared with the ischemia-reperfusion group. These findings indicate that probucol can protect testicular spermatogenesis by reducing overgeneration of reactive oxygen species by inhibiting E-selectin protein expression and neutrophil accumulation in the testis.

Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury

2006 ◽  
Vol 290 (6) ◽  
pp. H2247-H2256 ◽  
Author(s):  
Ivan Rubio-Gayosso ◽  
Steven H. Platts ◽  
Brian R. Duling
Keyword(s):  
Reactive Oxygen Species ◽  
Binding Sites ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Control Site ◽  
Oxygen Species ◽  
Heparin Binding ◽  
Heparin Binding Domain

The glycocalyx (Gcx) is a complex and poorly understood structure covering the luminal surface of endothelial cells. It is known to be a determinant of vascular rheology and permeability and may be a key control site for the vascular injuries caused by ischemia-reperfusion (I/R). We used intravital-microscopy to evaluate the effects of I/R injury on two properties of Gcx in mouse cremasteric microvessels: exclusion of macromolecules (anionic-dextrans) and intracapillary distribution of red blood cells (RBC). In this model, the Gcx is rapidly modified by I/R injury with an increase in 70-kDa anionic-dextran penetration without measurable effect on the penetration of 580-kDa anionic-dextran or on RBC exclusion. The effects of I/R injury appear to be mediated by the rapid production of reactive oxygen species (ROS) because they are ameliorated by the addition of exogenous superoxide dismutase-catalase. Intravenous application of allopurinol or heparin also inhibited the effects of I/R injury, and we interpret efficacy of allopurinol as evidence for a role for xanthine-oxidoreductase (XOR) in the response to I/R injury. Heparin, which is hypothesized to displace XOR from a heparin-binding domain in the Gcx, reduced the effects of I/R. The effects of I/R injury were also partially prevented or fully reversed by the intravascular infusion of exogenous hyaluronan. These data demonstrate: 1) the liability of Gcx during I/R injury; 2) the importance of locally produced ROS in the injury to Gcx; and 3) the potential importance of heparin-binding sites in modulating the ROS production. Our findings further highlight the relations between glycosaminoglycans and the pathophysiology of Gcx in vivo.

Intracellular generation of reactive oxygen species in endothelial cells exposed to anoxia-reoxygenation

1997 ◽  
Vol 272 (5) ◽  
pp. L897-L902 ◽  
Author(s):  
J. J. Zulueta ◽  
R. Sawhney ◽  
F. S. Yu ◽  
C. C. Cote ◽  
P. M. Hassoun
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Ros Formation ◽  
Oxide Synthase

Reactive oxygen species (ROS) play an important role in the pathogenesis of ischemia-reperfusion injury. Extracellular H2O2 generation from bovine pulmonary artery endothelial cells (EC) is known to increase in response to anoxia-reoxygenation (A-R). To determine potential sources of intracellular ROS formation in EC in response to A-R, a fluorometric assay based on the oxidation of 2',7'-dichlorofluorescin was used. Intracellular ROS production declined 40% during 6 h of anoxia (P < 0.05). After A-R, the rates of intracellular ROS formation increased to 148 +/- 9% (P < 0.001) that of normoxic EC (100 +/- 3%). In EC exposed to A-R, allopurinol and NG-methyl-L-arginine (L-NMMA), inhibitors of xanthine oxidase (XO) and nitric oxide synthase (NOS), respectively, reduced intracellular ROS formation by 25 +/- 1% (P < 0.001) and 36 +/- 4% (P < 0.01). Furthermore, at low doses (i.e., 20 microM), deferoxamine and diethylenetriaminepentaacetic acid (DTPA) significantly inhibited intracellular ROS formation. However, at 100 microM, only deferoxamine caused further reduction in DCF fluorescence. In summary, EC respond to A-R by generating increased amounts of XO- and NOS-derived intracellular ROS. The inhibition, to a similar extent, caused by allopurinol and L-NMMA, as well as the effect of deferoxamine and DTPA suggest that the ROS detected is peroxynitrite. Based on these findings and previous work, we conclude that EC generate ROS in response to A-R from at least two different sources: a plasma membrane-bound NADPH oxidase-like enzyme that releases H2O2 extracellularly and XO, which generates intracellular O2-, which in turn may react with nitric oxide to form peroxynitrite.

Sign in / Sign up

Export Citation Format

Share Document