Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR

Gielis, Jan F.; Beckers, Paul A. J.; Briedé, Jacob J.; Cos, Paul; Schil, Paul Van

doi:10.21037/atm.2017.03.32

Cited by 25 publications

(17 citation statements)

References 97 publications

(81 reference statements)

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“…The major cell compartments contributing to H2O2 production includes the mitochondria, the endoplasmic reticulum, and the peroxisomes [66]. Among the common ROS, H2O2 is a relatively stable molecule (about 1 millisecond half-life in a biological system) with decent diffusibility and selective reactivity in the cellular environment, which makes it a perfect ROS signaling molecule [69,70]. Currently, the most acknowledged mechanism of H2O2 acting as a signaling molecule is the direct oxidation of critical thiols on redox-sensitive proteins [71].…”

Section: H2o2 Signalingmentioning

confidence: 99%

Mechanisms by Which MnTE-2-PyP Suppresses Prostate Cancer Cell Growth

Zhu¹

2019

Free Radical Biology and Medicine

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MECHANISMS BY WHICH MNTE-2-PYP SUPPRESSES PROSTATE CANCER CELL GROWTH Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial membrane potential was unaffected. In addition, MnTE-2-PyP significantly increased NAD(P)+/NAD(P)H ratios in PC3 and LNCaP cells in a dose-dependent manner, which was mainly due to a reduction of cellular NAD(P)H pool. Correspondingly, we observed a significant decrease of activity in glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), which are major cellular NADPH producing enzymes in pentose phosphate pathway. A decrease of GSH/GSSG ratios were confirmed in MnTE-2-PyP-treated prostate cancer cells, which may result from the decreased glutathione reductase (GR) activity due to NADPH depletion. We also identified the oxidation of Ser/Thr protein phosphatase 1 beta catalytic subunit (PP1CB), and a decrease of PP1CB activity in MnTE-2-PyP-treated prostate cancer cells. One key protein, pRB, regulates cell cycle progression that is downstream target of PP1CB was hypophosphorylated in MnTE-2-PyP-treated prostate cancer cells. Significant increase of Ki67-negative populations were observed in both PC3 and LNCaP cells but overall cell cycle progression was not altered, which indicates xv TABLE OF CONTENTS

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Section: H2o2 Signalingmentioning

confidence: 99%

Mechanisms by Which MnTE-2-PyP Suppresses Prostate Cancer Cell Growth

Zhu¹

2019

Free Radical Biology and Medicine

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“…Recent studies have demonstrated that along with other inflammatory cascades and oxidative stress, nitroxidative stress also plays an important role in I/R-induced myocardial tissue injury (Plotnikov et al, 2007). Excessive production of nitric oxide (NO) from NOS and its highly reactive products such as peroxynitrite and superoxide has been reported to activate several apoptotic pathways leading to apoptotic cell death (Gielis et al, 2017). Furthermore, FTY720 also play important role in activating multiple signaling pathways including Akt/Erk1/2 and Pak1 to reduce IRI, cardiac arrhythmias and ventricular hypertrophy (Wang et al, 2018; Wang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective Effects of Sphingosine-1-Phosphate Receptor Immunomodulator FTY720 in a Clinically Relevant Model of Cardioplegic Arrest and Cardiopulmonary Bypass

et al. 2019

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Objective: FTY720, an immunomodulator derived from sphingosine-1-phosphate, has recently demonstrated its immunomodulatory, anti-inflammatory, anti-oxidant, anti-apoptotic and anti-inflammatory properties. Furthermore, FTY720 might be a key pharmacological target for preconditioning. In this preclinical model, we have investigated the effects of FTY720 on myocardium during reperfusion in an experimental model of cardioplegic arrest (CPA) and cardiopulmonary bypass. Methods: 30 Sprague–Dawley rats (300–350 g) were randomized into two groups: Group-A, treated with FTY720 1 mg/kg via intravenous cannulation, and Group-B, as control. After 15 min of treatment, rats underwent CPA for 30 min followed by initiation of extracorporeal life support for 2 h. Support weaning was done, and blood and myocardial tissues were collected for analysis. Hemodynamic parameters, inflammatory mediators, nitro-oxidative stress, neutrophil infiltration, immunoblotting analysis, and immunohistochemical staining were analyzed and compared between groups. Results: FTY720 treatment activated the Akt/Erk1/2 signaling pathways, reduced the level of inflammatory mediators, activated antiapoptotic proteins, and inhibited proapoptotic proteins, leading to reduced nitro-oxidative stress and cardiomyocyte apoptosis. Moreover, significant preservation of high-energy phosphates were observed in the FTY720-treated group. This resulted in improved recovery of left ventricular systolic and diastolic functions. Conclusion: The cardioprotective mechanism in CPA is associated with activation of prosurvival cell signaling pathways that prevents myocardial damage. FTY720 preserves high-energy phosphates attenuates myocardial inflammation and oxidative stress, and improves cardiac function.

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“…Lung ischemia reperfusion injury (LIRI), a severe complication which may lead to high morbidity and mortality, is defined as a temporary arrest of ventilation and/or blood supply in at least one lung [1] and paradoxically exacerbates further damage and dysfunction with re-establishment of reperfusion and reoxygenation [2]. LIRI, mainly occurs in lung transplantation or cardiopulmonary bypass, still is one of the greatest challenges in postoperative care, as it can lead to acute lung injury (ALI), even more severe lethal complications such as adult respiratory distress syndrome (ARDS)[3].…”

Section: Introductionmentioning

confidence: 99%

“…While LIRI was a complex process, recent research had highlighted the importance in oxidative stress responses, inflammation [1, 5], innate immune responses [2, 6, 7] and endothelial barrier function [2, 7]. When an organ began to suffer hypoxia or ischemia, a series of cascade reactions would be initiated.…”

Section: Introductionmentioning

confidence: 99%

The Nox1/Nox4 inhibitor attenuates acute lung injury induced by ischemia-reperfusion in mice

Cui

Wang²,

et al. 2018

PLoS ONE

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Lung ischemia and reperfusion injury (LIRI) were mediated by several processes including over-production of reactive oxygen species (ROS) and inflammatory activation. ROS generated by nicotinamide adenine dinucletide phosphate (NADPH) oxidase (Nox) may play a pivotal role in pathophysiological changes in a range of disease. However, it was poorly understood in LIRI. Thus, the purpose of our study was to explore whether GKT137831, as a special dual inhibitor of Nox1 and 4, could alleviate LIRI in mice model and explore the minimal dose. According to the protocol, this study was divided into two parts. The first part was to determine the minimal dose of Nox1/4 inhibitor in attenuating LIRI via histopathology and apoptosis analysis. Eighteen C57BL/6J male wild-type mice were randomly divided in to sham, 2.5Nox+sham, 5.0Nox+sham, IR, 2.5Nox+IR and 5.0Nox+IR groups. According to the different group, mice were pretreated with corresponding dose of Nox1/4 inhibitors or normal saline. After LIRI, the results showed 5.0mg/kg Nox1/4 inhibitor could be considered as the minimal dose to alleviate injury by decreasing of lung injury score and the number of TUNEL-positive cells. The second part was to further verify the benefit of 5.0mg/kg Nox1/4 inhibitor in lung protective effects. Thirty-seven C57BL/6J male wild-type mice were divided in to sham, IR and 5.0Nox+IR groups randomly. The results showed that expressions of inflammatory, autophagy cytokines were markedly elevated and PH value was declined after LIRI. However, 5.0 mg/kg Nox1/4 inhibitor significantly attenuated cytokine production as reflected by immunohistochemistry, western blotting and Q-PCR analysis. In conclusion, our findings suggested that 5.0mg/kg Nox1/4 inhibitor contributed to protect lung tissue damage after LIRI via the suppression of inflammatory and autophagy activation.

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Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR

Cited by 25 publications

References 97 publications

Mechanisms by Which MnTE-2-PyP Suppresses Prostate Cancer Cell Growth

Mechanisms by Which MnTE-2-PyP Suppresses Prostate Cancer Cell Growth

Cardioprotective Effects of Sphingosine-1-Phosphate Receptor Immunomodulator FTY720 in a Clinically Relevant Model of Cardioplegic Arrest and Cardiopulmonary Bypass

The Nox1/Nox4 inhibitor attenuates acute lung injury induced by ischemia-reperfusion in mice

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