scholarly journals Protection against ischemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: involvement of mitochondrial KATP channels and reactive oxygen species

2009 ◽  
pp. 9-19 ◽  
Author(s):  
J Matejíková ◽  
J Kucharská ◽  
M Pintérová ◽  
D Pancza ◽  
T Ravingerová
Keyword(s):  
Reactive Oxygen Species ◽  
Rat Heart ◽  
Ventricular Arrhythmias ◽  
Myocardial Dysfunction ◽  
Reactive Oxygen ◽  
Katp Channels ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Katp Channels

Ischemic preconditioning (I-PC) induced by brief episodes of ischemia and reperfusion (I/R) protects the heart against sustained I/R. Although activation of mitochondrial KATP channels (mitoKATP) interacting with reactive oxygen species (ROS) has been proposed as a key event in this process, their role in the antiarrhythmic effect is not clear. This study was designed: 1) to investigate the involvement of mito KATP opening in the effect of I-PC (1 cycle of I/R, 5 min each) on ventricular arrhythmias during test ischemia (TI, 30-min LAD coronary artery occlusion) in Langendorff-perfused rat hearts and subsequent postischemic contractile dysfunction, and 2) to characterize potential mechanisms of protection conferred by I-PC and pharmacological PC induced by mito KATP opener diazoxide (DZX), with particular regards to the modulation of ROS generation. Lipid peroxidation (an indicator of increased ROS production) was determined by measurement of myocardial concentration of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in nonischemic controls, non-preconditioned and preconditioned hearts exposed to TI, I-PC alone, as well as after pretreatment with DZX, mito KATP blocker 5-hydroxydecanoate (5-HD) and antioxidant N-acetylcysteine (NAC). Total number of ventricular premature beats (VPB) that occurred in the control hearts (518±71) was significantly (P<0.05) reduced by I-PC (195±40), NAC (290±56) and DZX (168±22). I-PC and NAC suppressed an increase in CD and TBARS caused by ischemia indicating lower production of ROS. On the other hand, I-PC and DZX themselves moderately enhanced ROS generation, prior to TI. Bracketing of I-PC with 5-HD suppressed both, ROS production during PC and its cardioprotective effect. In conclusion, potential mechanisms of protection conferred by mito KATP opening in the rat heart might involve a temporal increase in ROS production in the preconditioning phase triggering changes in the pro/antioxidant balance in the myocardium and attenuating ROS production during subsequent prolonged ischemia.

scholarly journals Treatment of Rats With Hypolipidemic Compound Pirinixic Acid Protects Their Hearts Against Ischemic Injury: Are Mitochondrial KATP Channels and Reactive Oxygen Species Involved?

2013 ◽  
pp. 577-584 ◽  
Author(s):  
M. NEMČEKOVÁ ◽  
S. ČARNICKÁ ◽  
M. FERKO ◽  
M. MURÁRIKOVÁ ◽  
V. LEDVÉNYIOVÁ ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Rat Heart ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Katp Channels ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Protective Effects ◽  
Mitochondrial Katp Channels

Hypolipidemic compound pirinixic acid (WY-14643, WY) is known to exert pleiotropic (other than primary) effects, such as activation of peroxisome proliferator-activated receptors (PPAR-α), transcription factors regulating different cardiac functions. Their role in ischemia-reperfusion (I/R) injury and cardioprotection is less clear, although protective effects of PPAR agonists have been documented. This study was designed to explore the effects of WY on the I/R injury in the rat heart and potential mechanisms involved, including mitochondrial KATP channels (mitoKATP) opening and production of reactive oxygen species (ROS). Langendorff-perfused hearts of rats intragastrally treated with WY (3 mg/kg/day) for 5 days and of control animals were subjected to 30-min global ischemia and 2-h reperfusion with or without 15-min perfusion with mitoKATP blocker 5-hydroxydecanoate (5-HD) prior to I/R. Evaluation of the infarct size (IS, TTC staining) served as the main end-point of protection. Lipid peroxidation (a marker of ROS production) was determined by measurement of myocardial concentration of conjugated dienes (CD), whereas protein expression of endothelial NO synthase was analysed by Western blotting. A 2-fold increase in the cardiac protein levels of eNOS after treatment with WY was accompanied by lower post-I/R levels of CD compared with those in the hearts of untreated controls, although WY itself enhanced ROS generation prior to ischemia. IS was reduced by 47 % in the hearts of WY-treated rats (P<0.05), and this effect was reversed by 5-HD. Results suggest that PPAR-α activation may confer protection against lethal I/R injury in the rat heart that involves up-regulation of eNOS, mitoKATP opening and reduced oxidative stress during I/R.

scholarly journals Reactive Oxygen Species in Host Plant Are Required for an Early Defense Response against Attack of Stagonospora nodorum Berk. Necrotrophic Effectors SnTox

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1586
Author(s):  
Svetlana Veselova ◽  
Tatyana Nuzhnaya ◽  
Guzel Burkhanova ◽  
Sergey Rumyantsev ◽  
Igor Maksimov
Keyword(s):  
Reactive Oxygen Species ◽  
Early Stage ◽  
Reactive Oxygen ◽  
Triticum Aestivum L ◽  
Redox Status ◽  
Stagonospora Nodorum ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Necrotrophic Effectors

Reactive oxygen species (ROS) play a central role in plant immune responses. The most important virulence factors of the Stagonospora nodorum Berk. are multiple fungal necrotrophic effectors (NEs) (SnTox) that affect the redox-status and cause necrosis and/or chlorosis in wheat lines possessing dominant susceptibility genes (Snn). However, the effect of NEs on ROS generation at the early stages of infection has not been studied. We studied the early stage of infection of various wheat genotypes with S nodorum isolates -Sn4VD, SnB, and Sn9MN, carrying a different set of NE genes. Our results indicate that all three NEs of SnToxA, SnTox1, SnTox3 significantly contributed to cause disease, and the virulence of the isolates depended on their differential expression in plants (Triticum aestivum L.). The Tsn1–SnToxA, Snn1–SnTox1and Snn3–SnTox3 interactions played an important role in inhibition ROS production at the initial stage of infection. The Snn3–SnTox3 inhibited ROS production in wheat by affecting NADPH-oxidases, peroxidases, superoxide dismutase and catalase. The Tsn1–SnToxA inhibited ROS production in wheat by affecting peroxidases and catalase. The Snn1–SnTox1 inhibited the production of ROS in wheat by mainly affecting a peroxidase. Collectively, these results show that the inverse gene-for gene interactions between effector of pathogen and product of host sensitivity gene suppress the host’s own PAMP-triggered immunity pathway, resulting in NE-triggered susceptibility (NETS). These results are fundamentally changing our understanding of the development of this economical important wheat disease.

Abstract 19967: Differential Roles of the NADPH-Oxidase 1 and 2 in Platelet Activation and Thrombosis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Michael K Delaney ◽  
Kyungho Kim ◽  
Brian Estevez ◽  
Aleksandra Stojanovic-Terpo ◽  
Bo Shen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Platelet Activation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
General Role ◽  
Glycoprotein Vi ◽  
Activation Pathways

Objective: Reactive oxygen species (ROS) generated from activated platelets is known to regulate platelet activation. However, it remains unclear whether and how different isoforms of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases (NOXs) play roles in different platelet activation pathways. Here we investigated the role of NOX1 and NOX2 in different platelet activation pathways using NOX1 and NOX2 knockout mice. Approach and Results: NOX1-/- platelets showed selective defects in G protein coupled receptor (GPCR)-mediated platelet activation induced by thrombin, protease-activated receptor 4 agonist peptide (PAR4AP) and thromboxane A2 analog U46619, but was not affected in platelet activation induced by collagen-related peptide (CRP), a glycoprotein VI (GPVI) agonist. In contrast, NOX2-/- platelets showed potent inhibition of CRP-induced platelet activation, and also showed partial inhibition of thrombin-induced platelet aggregation and secretion. Consistently, production of reactive oxygen species (ROS) was inhibited in NOX1-/- platelets stimulated with thrombin, but not CRP, whereas NOX2-/- platelets showed reduced ROS generation induced by CRP or thrombin. Interestingly, laser-induced arterial thrombosis was impaired in NOX2-/- mice, and in thrombocytopenic mice transfused with NOX2-/- platelets, suggesting an important role for NOX2-dependent platelet ROS production in the laser-induced injury model of thrombosis. Conclusions: NOX1 and NOX2 play differential roles in different platelet activation pathways: NOX1 mediates GPCR-mediated ROS production and platelet activation, whereas NOX2 plays a general role in GPVI- and GPCR-induced ROS production and platelet activation in vitro , and in laser-induced thrombosis in vivo .

scholarly journals Mitochondrial uncoupling does not decrease reactive oxygen species production after ischemia-reperfusion

2014 ◽  
Vol 307 (7) ◽  
pp. H996-H1004 ◽  
Author(s):  
Ricardo Quarrie ◽  
Daniel S. Lee ◽  
Levy Reyes ◽  
Warren Erdahl ◽  
Douglas R. Pfeiffer ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Sprague Dawley ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Ros ◽  
Ros Formation

Cardiac ischemia-reperfusion (IR) leads to myocardial dysfunction by increasing production of reactive oxygen species (ROS). Mitochondrial H+ leak decreases ROS formation; it has been postulated that increasing H+ leak may be a mechanism of decreasing ROS production after IR. Ischemic preconditioning (IPC) decreases ROS formation after IR, but the mechanism is unknown. We hypothesize that pharmacologically increasing mitochondrial H+ leak would decrease ROS production after IR. We further hypothesize that IPC would be associated with an increase in the rate of H+ leak. Isolated male Sprague-Dawley rat hearts were subjected to either control or IPC. Mitochondria were isolated at end equilibration, end ischemia, and end reperfusion. Mitochondrial membrane potential (mΔΨ) was measured using a tetraphenylphosphonium electrode. Mitochondrial uncoupling was achieved by adding increasing concentrations of FCCP. Mitochondrial ROS production was measured by fluorometry using Amplex-Red. Pyridine dinucleotide levels were measured using HPLC. Before IR, increasing H+ leak decreased mitochondrial ROS production. After IR, ROS production was not affected by increasing H+ leak. H+ leak increased at end ischemia in control mitochondria. IPC mitochondria showed no change in the rate of H+ leak throughout IR. NADPH levels decreased after IR in both IPC and control mitochondria while NADH increased. Pharmacologically, increasing H+ leak is not a method of decreasing ROS production after IR. Replenishing the NADPH pool may be a means of scavenging the excess ROS thereby attenuating oxidative damage after IR.

scholarly journals Impact of CD14 on Reactive Oxygen Species Production from Human Leukocytes Primed byEscherichia coliLipopolysaccharides

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Dmitry S. Kabanov ◽  
Olga Yu. Vwedenskaya ◽  
Marina A. Fokina ◽  
Elena M. Morozova ◽  
Sergey V. Grachev ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Polymorphonuclear Neutrophils ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Human Pmns ◽  
Species Production ◽  
The Impact ◽  
Priming Activity

Lipopolysaccharides (LPS) from Gram-negative bacteria prime human polymorphonuclear neutrophils (PMNs) via multicomponent receptor cluster including CD14 and MD-2·TLR4 for the enhanced release of reactive oxygen species (ROS) were triggered by bacterial derived peptideN-formyl-methionyl-leucyl-phenylalanine (fMLP). In this study, we investigated the impact of CD14 on LPS-induced priming of human PMNs for fMLP-triggered ROS generation (respiratory or oxidative) burst. Monoclonal antibodies against human CD14 (mAbs) as well as isotype-matched IgG2a did not influence significantly fMLP-triggered ROS production from LPS-unprimed PMNs. Anti-CD14 mAbs (clone UCHM-1) attenuated LPS-induced priming of PMNs as it had been mirrored by fMLP-triggered decrease of ROS production. Similar priming activity of S-LPS or Re-LPS fromEscherichia colifor fMLP-triggered ROS release from PMNs was found. Obtained results suggest that glycosylphosphatidylinositol-anchored CD14 is the key player in LPS-induced PMN priming for fMLP-triggered ROS production. We believe that blockade of CD14 on the cell surface and clinical use of anti-CD14 mAbs or their Fab fragments may diminish the production of ROS and improve outcomes during cardiovascular diseases manifested by LPS-induced inflammation.

Reactive Oxygen Species Are Differentially Regulated in Chronic Myeloid Leukemia Versus Philadelphia Negative Myeloproliferative Neoplasms

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4215-4215
Author(s):  
Estelle Guerin ◽  
Francis Belloc ◽  
Gabriel Etienne ◽  
Pierre Duffau ◽  
Francois-Xavier Mahon ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Peripheral Blood ◽  
Myeloproliferative Neoplasms ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Separate Analysis ◽  
Ros Production ◽  
Oxygen Species ◽  
Normal Cells

Abstract Deregulation of tyrosine-kinases is a characteristic of most Myeloproliferative Neoplasms (MPN); evolution from chronic phase to acute leukemia depends on the acquisition of additional mutations. Reactive Oxygen Species (ROS), the production of which is increased by tyrosine-kinase activation, can be responsible for additional mutations. The role of ROS in generating genetic aberrations has been mainly studied in BCR-ABL-positive cell lines. Little is known of ROS metabolism in primary cells from CML or Philadelphia-negative MPN (Ph-MPN). After informed consent, cells from blood or bone marrow were obtained from patients diagnosed with CML (12 bone marrow (BM), 8 peripheral blood (PB)), or Ph-MPN (4 Polycythemia Vera, 6 Essential Thrombocythemia, 3 Primary Myelofibroses, 2 atypical CML) and from healthy donors (bone marrow donors) or patients devoid of hematological disease undergoing thoracotomy. Cells were incubated with DCFDA, a fluorogenic marker of ROS production, labelled with an anti-CD45 antibody, stimulated with either the oxidant hydrogen peroxide (H2O2) or the PKC activator Phorbol Myristate Acetate (PMA), and analysed for ROS production by flow cytometry. CD45/SSC gating allowed separate analysis of granulocytes, monocytes or lymphocytes. The basal level of ROS was not higher in CML cells as compared to normal BM or PB leukocytes. It was even significantly lower in CML lymphocytes, either from the BM (2.35 Arbitrary Units vs 8.3 AU, p=5.5 10−5) or PB (2.47 AU vs 7.4 AU, p=3.10−5) and in CML granulocytes from peripheral blood (14 AU vs 45 AU, p =10 −5), but not bone marrow. The ROS levels of Ph-MPN cells were similar or slightly higher than control cells. Upon H2O2 stimulation however, ROS production increased significantly more in CML cells as compared to normal cells (6 fold increase), whatever the cell type (granulocytes, monocytes and lymphocytes) or their origin (PB or BM). In contrast, for Ph-MPN cells, H2O2-stimulated ROS production was close to that of normal cells, with only BM lymphocytes showing ROS generation four fold higher than control BM lymphocytes. After PMA stimulation, which yielded a more modest ROS production than H2O2, CML cells behaved similarly to normal cells, whereas ROS production was four fold higher in Ph-MPN cells, whatever their type and origin. In conclusion, ROS levels at the basal stage are not higher in MPN cells, whether they are Philadelphia positive or negative, as compared to normal cells. Various kinds of stimulation induce different patterns of response, CML cells being more sensitive to oxidants whereas Ph-MPN cells respond more to the cytokine-mimicking agent PMA. These results suggest that the mechanisms of ROS generation and thus of genetic instability are different in CML and Ph-MPN.

Noradrenaline Protects In Vivo Rat Heart Against Infarction and Ventricular Arrhythmias Via Nitric Oxide and Reactive Oxygen Species

2011 ◽  
Vol 169 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Alireza Imani ◽  
Mahdieh Faghihi ◽  
Sayyed Shahabeddin Sadr ◽  
Somayeh Sadeghi Niaraki ◽  
Ali Mohammad Alizadeh
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Rat Heart ◽  
Ventricular Arrhythmias ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
In Vivo Rat Heart
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