Journal articles on the topic 'Scavenger molecules of oxygen reactive species'
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Misra, Hari S., Nivedita P. Khairnar, Atanu Barik, K. Indira Priyadarsini, Hari Mohan, and Shree K. Apte. "Pyrroloquinoline-quinone: a reactive oxygen species scavenger in bacteria." FEBS Letters 578, no. 1-2 (November 4, 2004): 26–30. http://dx.doi.org/10.1016/j.febslet.2004.10.061.
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Festjens, N., M. Kalai, J. Smet, A. Meeus, R. Van Coster, X. Saelens, and P. Vandenabeele. "Butylated hydroxyanisole is more than a reactive oxygen species scavenger." Cell Death & Differentiation 13, no. 1 (September 2, 2005): 166–69. http://dx.doi.org/10.1038/sj.cdd.4401746.
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Mahajan, Nitin, Heidi Y. Shi, Thomas J. Lukas, and Ming Zhang. "Tumor-suppressive Maspin Functions as a Reactive Oxygen Species Scavenger." Journal of Biological Chemistry 288, no. 16 (March 7, 2013): 11611–20. http://dx.doi.org/10.1074/jbc.m112.410852.
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Mori, Hiroko, Toshiyuki Arai, Hisanari Ishii, Nobuyuki Endo, Toshinori Suzuki, and Kazuhiko Fukudal. "Pterin-6-aldehyde, Xanthine Oxidase Inhibitor and Superoxide Scavenger, Directly React with Peroxynitrite." Pteridines 10, no. 1 (February 1999): 32–34. http://dx.doi.org/10.1515/pteridines.1999.10.1.32.
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The effect of pterin-6-aldehyde (P6A), xanthine oxidase inhibitor and superoxide scavenger, on the production of nitrotyrosine as a footprint of tyrosine nitration by peroxynitrite, was compared with that of uric acid, a peroxynitrite scavenger. The amounts of tyrosine, P6A and nitrotyrosine were quantified using reversed-phase high-performance liquid chromato-graphy (RP-HPLC). P6A suppressed nitrotyrosine formation less effectively than uric acid, that is, 0.25 mM P6A reduced nitrotyrosine formation to 67.9± 10.8%, while 0.025 mM uric acid reduced it to 34.2± 1.6%. In living systems, peroxynitrite is generated by the reaction of super-oxide with nitric oxide and has a variety of toxic effects. Our results show that P6A is not necessarily a strong scavenger of peroxynitrite. However, since P6A is a potent scavenger of superoxide, P6A is thought to totally suppress peroxynitrite generation. Compounds that scavenge both superoxide and peroxynitrite may be useful in tissue damage in which reactive oxygen species are involved.
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Singh, Neha, Satish C. Bhatla, and Vadim Demidchik. "Plants and human beings engage similar molecular crosstalk with nitric oxide under stress conditions." Functional Plant Biology 46, no. 8 (2019): 695. http://dx.doi.org/10.1071/fp19018.
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Human beings and plants experience a variety of stress conditions and adapt themselves through novel molecular crosstalk in their cellular constituents. Nitric oxide (NO), haemoglobin and melatonin interact with each other not only in blood stream of human beings, but also in the cells and metabolically active conducting strands of plants. Specialised sites of biosynthesis and differential intracellular spatial distribution of these molecules have been clearly demonstrated by the authors in plant systems. This has led to an understanding of the role of these molecules under salt stress conditions experienced by plants: NO is a modulator of enzyme activity through S-nitrosylation and tyrosine nitration, haemoglobin (phytoglobin) is an NO scavenger, and melatonin is a reactive oxygen species (ROS) scavenger involved in key crosstalk in both plants and humans facing stress. Our recent work on heme oxygenase (HO) activity modulation by stress in plants, and its interaction with NO, further demonstrates common features of molecular crosstalk in protecting plants and human beings from stress.
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Voronkova, Y. S., O. S. Voronkova, V. A. Gorban, and K. K. Holoborodko. "Oxidative stress, reactive oxygen species, antioxidants: a review." Ecology and Noospherology 29, no. 1 (May 9, 2018): 52–55. http://dx.doi.org/10.15421/031809.
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Oxidative stress is a disturbance of the balance between the production of reactive oxygen species (ROS) and antioxidants. Oxidative stress is caused by the presence of any of a number of reactive oxygen species, which the cell is unable to counterbalance. The result is damage to one or more biomolecules including DNA, RNA, proteins and lipids. Oxidative stress has been implicated in the natural aging process as well as a variety of disease states, such as neoplastic, metabolic, neurological etc., accompanied by different complications. Risk factors of generation of oxidative stress are oxidizing species, induced by pathologies include alcohol consumption, cigarette smoking, diet, gender, geographic location specifically at high altitude and occupation. ROS are composed of superoxide, hydroxyl, peroxyl, hydroperoxyl and alkoxyl radicals, hydrogen peroxide and singlet oxygen and ozone. These compounds produced endogenous in reaction of autooxidation in respiratory chaine of bioobjects. Among exogenous sources of ROS can be listed exposure of pollutants, toxins, heavy metals, drugs with different chemical origin and effects, radiation, electromagnetic fields, alcohol, cigarette smoke, stresses, allergies, dietary factors, temperature and microscopic form of life, such as bacteria, yeasts, viruses etc. The oxidative stress in biological systems is often characterized by increase in the formation of radicals; decrease in small-molecular-weight and lipid soluble antioxidants; disturbance in cellular redox balance; oxidative damage to cellular components (biomacromolecules). The presence of oxidative stress may be tested in one of three ways: direct measurement of the ROS; measurement of the resulting damage to biomolecules; and detection of antioxidant levels. Directly measuring ROS might seem the preferred method, but many reactive oxygen species are extremely unstable and difficult to measure directly. Many markers of damage are extremely stable and therefore provide a more reliable method to measure oxidative stress. Another approach is to measure the levels of antioxidant enzymes and other redox molecules which serve to counterbalance ROS generated in the cell. At the same time, it must emphasize that oxidative stress not only has a cytotoxic effect, but also plays an important role in the modulation of messengers that regulate essential cell membrane functions, which are vital for survival. For prevention of oxidative stress cells produce or uptake antioxidants – substance significantly delays or prevents oxidation of that substrate. Antioxidants may be enzymatic and non-enzymatic in nature in which enzymatic system directly or indirectly help in defence against the ROS. Antioxidants are involved in the prevention of oxidants and ROS formation; exhibits scavenger of ROS; and repairs the oxidized molecules through sources like dietary or consecutive antioxidants. Among non-enzymatic antioxidants distinguished glutathione, α-tocopherol, ascorbic acid, beta-carotene, and uric acid; these are mostly considered to be chain-breaking antioxidants in that they interrupt the auto-catalytic spread of radical reactions. Among enzymatic antioxidants most known superoxide dismutase, catalase, glutathione-SH peroxidase. The significant correlation found between ROS, parameters of oxidative stress and pathology indicate that there is a need in finding of measures of prevention of endo- and exogenous factors provoke their generation. There is a need to continue to explore the relationship between free radicals, pathological processes and the complications of them, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of complications, in an effort to expand treatment options. Improvement of complications control seems to be a beneficial factor to decrease oxidative stress. For a better investigation of oxidative stress, it would be wise to supplement the clinical research by determination of special products typical for oxidative stress that let to understand mechanism of some pathological processes more clearly.
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Liu, Fu-Chao, Hsin-I. Tsai, and Huang-Ping Yu. "Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress-Mediated Reperfusion Injury." Oxidative Medicine and Cellular Longevity 2015 (2015): 1–15. http://dx.doi.org/10.1155/2015/568634.
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Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed.
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Rodrigues, Eliseu, Lilian R. B. Mariutti, Adélia F. Faria, and Adriana Z. Mercadante. "Microcapsules containing antioxidant molecules as scavengers of reactive oxygen and nitrogen species." Food Chemistry 134, no. 2 (September 2012): 704–11. http://dx.doi.org/10.1016/j.foodchem.2012.02.163.
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Kovary, Karla, Tatiana S. Louvain, Maria C. Costa e. Silva, Franco Albano, Barbara B. M. Pires, Gustavo A. T. Laranja, Celso L. S. Lage, and Israel Felzenszwalb. "Biochemical behaviour of norbixin duringin vitroDNA damage induced by reactive oxygen species." British Journal of Nutrition 85, no. 4 (April 2001): 431–40. http://dx.doi.org/10.1079/bjn2000287.
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Naturally occurring antioxidants such as carotenoids are extensively studied for their potential in reducing the risk for cancer and other chronic diseases. In the present study, the radical-scavenger activity of the food additive norbixin, a water-soluble carotenoid extracted fromBixa orellanaseeds and commercialized as annatto, was evaluated under conditions of DNA damage induced by reactive oxygen species, particularly by hydroxyl radicals. The cell-free scavenger activity of norbixin was evaluated using plasmid DNA as target molecule and Sn2+or Fe2+as oxidant. The addition of H2O2enhanced DNA breakage induced by metal ions, particularly Fe2+. Under these conditions, norbixin started to protect plasmid DNA against single- and double-strand breakage at a metal:norbixin ratio of 1:1 (Sn2+) and 1:10 (Fe2+). However, at lower ratios to Sn2+, norbixin enhanced Sn2+-induced DNA breakage (P<0.05). The ability of norbixin to protect genomic DNA against oxidative damage was assessed in murine fibroblasts submitted to H2O2-induced oxidative stress and the results were evaluated by the comet assay. Under low serum conditions (2 % fetal bovine serum (FBS)), a protective effect of norbixin against H2O2-induced DNA breakage was inversely related to its concentration, a protection ranging from 41 % (10 μM) TO 21 % (50 μm). At higher concentrations of norbixin, however, oxidative DNA breakage was still enhanced, even in the presence of a high serum concentration (10 % FBS). Under normal conditions, norbixinper sehas no detectable genotoxic or cytotoxic effects on murine fibroblasts. The antimutagenic potential of norbixin against oxidative mutagens was also evaluated by theSalmonella typhimuriumassay, with a maximum inhibition of 87 % against the mutagenicity induced by H2O2. Although plasmid DNA and Ames data indicated that norbixin can protect DNA against oxidative damage, it seems to be a risky guardian of genomic DNA as it can also increase the extent of oxidative damage.
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Kim, Hyoung Jin, Sun Young Koo, Bong-Hyun Ahn, Oeuk Park, Doo Hoe Park, Dong Ook Seo, Jong Heon Won, et al. "NecroX as a novel class of mitochondrial reactive oxygen species and ONOO− scavenger." Archives of Pharmacal Research 33, no. 11 (November 2010): 1813–23. http://dx.doi.org/10.1007/s12272-010-1114-4.
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Nag, Okhil K., Jawad Naciri, Kwahun Lee, Eunkeu Oh, Bethany Almeida, and James B. Delehanty. "Liquid Crystal Nanoparticle Conjugates for Scavenging Reactive Oxygen Species in Live Cells." Pharmaceuticals 15, no. 5 (May 14, 2022): 604. http://dx.doi.org/10.3390/ph15050604.
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The elevated intracellular production of or extracellular exposure to reactive oxygen species (ROS) causes oxidative stress to cells, resulting in deleterious irreversible biomolecular reactions (e.g., lipid peroxidation) and disease progression. The use of low-molecular weight antioxidants, such as 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), as ROS scavengers fails to achieve the desired efficacy because of their poor or uncontrolled cellular uptake and off-target effects, such as dysfunction of essential redox homeostasis. In this study, we fabricated a liquid crystal nanoparticle (LCNP) conjugate system with the fluorescent dye perylene (PY) loaded in the interior and poly (ethylene glycol) (PEG) decorated on the surface along with multiple molecules of TEMPO (PY-LCNP-PEG/TEMPO). PY-LCNP-PEG/TEMPO exhibit enhanced cellular uptake, and efficient ROS-scavenging activity in live cells. On average, the 120 nm diameter PY-LCNPs were conjugated with >1800 molecules of TEMPO moieties on their surface. PY-LCNP-PEG/TEMPO showed significantly greater reduction in ROS activity and lipid peroxidation compared to free TEMPO when the cells were challenged with ROS generating agents, such as hydrogen peroxide (H2O2). We suggest that this is due to the increased local concentration of TEMPO molecules on the surface of the PY-LCNP-PEG/TEMPO NPs, which efficiently bind to the plasma membrane and enter cells. Overall, these results demonstrate the enhanced capability of TEMPO-conjugated LCNPs to protect live cells from oxidative stress by effectively scavenging ROS and reducing lipid peroxidation.
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Su, Bor-Chyuan, Chieh-Yu Pan, and Jyh-Yih Chen. "Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells." Cancers 11, no. 2 (February 1, 2019): 171. http://dx.doi.org/10.3390/cancers11020171.
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Antimicrobial peptide tilapia piscidin 4 (TP4) from Oreochromis niloticus exhibits potent bactericidal and anti-tumorigenic effects. In a variety of cancers, the mutation status of p53 is a decisive factor for therapeutic sensitivity. Therefore, we investigated the impact of p53 status on TP4-induced cytotoxicity in glioblastoma cell lines and the molecular mechanisms that govern cytotoxic effects. Both U87MG (wild-type/WT p53) and U251 (mutant p53) glioblastoma cell lines were sensitive to TP4-induced cytotoxicity. The necrosis inhibitors Necrostatin-1 and GSK’872 attenuated TP4-induced cytotoxicity, and TP4 treatment induced the release of cyclophilin A, a biomarker of necrosis. Moreover, TP4 induced mitochondrial hyperpolarization and dysfunction, which preceded the elevation of intracellular reactive oxygen species, DNA damage, and necrotic cell death in both U87MG and U251 glioblastoma cells. p38 was also activated by TP4, but did not contribute to cytotoxicity. SB202190, a specific p38 inhibitor, enhanced TP4-induced oxidative stress, mitochondrial dysfunction, and cytotoxicity, suggesting a protective role of p38. Furthermore, TP4-induced cytotoxicity, oxidative stress, phosphorylation of p38, and DNA damage were all attenuated by the mitochondrial-targeted reactive oxygen species (ROS) scavenger MitoTEMPO, or the reactive oxygen species scavenger N-acetyl-L-cysteine. Based on these data, we conclude that TP4 induces necrosis in both WT and mutant p53 glioblastoma cells through a mitochondrial ROS-dependent pathway.
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Matsuda, Fumio, Hisashi Miyagawa, and Tamio Ueno. "Involvement of Reactive Oxygen Species in the Induction of (S)-N-p-Coumaroyloctopamine Accumulation by β-1,3-Glucooligosaccharide Elicitors in Potato Tuber Tissues." Zeitschrift für Naturforschung C 56, no. 3-4 (April 1, 2001): 228–34. http://dx.doi.org/10.1515/znc-2001-3-410.
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Abstract Treatment of potato tuber tissues with β-1,3-glucooligosaccharide induces accumulation of (S)-N-p-coumaroyloctopamine (p-CO). We examined the role of reactive oxygen species (ROS) and nitric oxide (NO) in the signal transduction leading to p-CO accumulation. Induction was suppressed by an NADPH -oxidase inhibitor, diphenyleneiodonium chloride, and oxygen radical scavengers. H2O2 was generated in the tuber tissue within a few minutes of treatment with β-1,3-glucooligosaccharide. On the other hand, treatment with NO specific scavenger, nitric oxide synthase inhibitor, and serine protease inhibitor did not inhibit p -CO induction. Our findings suggest that ROS generated by the action o f NADPH -oxidase play an important role in this system, while NO and serine protease are unlikely to be involved in this process.
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Bao, Hui-Fang, John Z. Song, Billie J. Duke, He-Ping Ma, Donald D. Denson, and Douglas C. Eaton. "Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species." American Journal of Physiology-Cell Physiology 303, no. 11 (December 1, 2012): C1129—C1138. http://dx.doi.org/10.1152/ajpcell.00139.2012.
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Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability ( Po) and the number of active ENaC in patches ( N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC Po and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde.
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Yamauchi, Shota, Shoji Mano, Kazusato Oikawa, Kazumi Hikino, Kosuke M. Teshima, Yoshitaka Kimori, Mikio Nishimura, Ken-ichiro Shimazaki, and Atsushi Takemiya. "Autophagy controls reactive oxygen species homeostasis in guard cells that is essential for stomatal opening." Proceedings of the National Academy of Sciences 116, no. 38 (September 4, 2019): 19187–92. http://dx.doi.org/10.1073/pnas.1910886116.
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Reactive oxygen species (ROS) function as key signaling molecules to inhibit stomatal opening and promote stomatal closure in response to diverse environmental stresses. However, how guard cells maintain basal intracellular ROS levels is not yet known. This study aimed to determine the role of autophagy in the maintenance of basal ROS levels in guard cells. We isolated the Arabidopsis autophagy-related 2 (atg2) mutant, which is impaired in stomatal opening in response to light and low CO2 concentrations. Disruption of other autophagy genes, including ATG5, ATG7, ATG10, and ATG12, also caused similar stomatal defects. The atg mutants constitutively accumulated high levels of ROS in guard cells, and antioxidants such as ascorbate and glutathione rescued ROS accumulation and stomatal opening. Furthermore, the atg mutations increased the number and aggregation of peroxisomes in guard cells, and these peroxisomes exhibited reduced activity of the ROS scavenger catalase and elevated hydrogen peroxide (H2O2) as visualized using the peroxisome-targeted H2O2 sensor HyPer. Moreover, such ROS accumulation decreased by the application of 2-hydroxy-3-butynoate, an inhibitor of peroxisomal H2O2-producing glycolate oxidase. Our results showed that autophagy controls guard cell ROS homeostasis by eliminating oxidized peroxisomes, thereby allowing stomatal opening.
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Palma, José M., and Isabel Seiquer. "To Be or Not to Be… An Antioxidant? That Is the Question." Antioxidants 9, no. 12 (December 5, 2020): 1234. http://dx.doi.org/10.3390/antiox9121234.
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The concept of antioxidants refers to a substance with the capacity to either directly scavenge or indirectly prevent the formation of pro-oxidant molecules, basically associated to the so called reactive oxygen species (ROS) [...]
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Yin, Jun-Jie, Fang Lao, Jie Meng, Peter P. Fu, Yuliang Zhao, Gengmei Xing, Xueyun Gao, et al. "Inhibition of Tumor Growth by Endohedral Metallofullerenol Nanoparticles Optimized as Reactive Oxygen Species Scavenger." Molecular Pharmacology 74, no. 4 (July 17, 2008): 1132–40. http://dx.doi.org/10.1124/mol.108.048348.
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Yu, Tzu-Jung, Jun-Ping Shiau, Jen-Yang Tang, Chia-Hung Yen, Ming-Feng Hou, Yuan-Bin Cheng, Chih-Wen Shu, and Hsueh-Wei Chang. "Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells." Antioxidants 11, no. 7 (July 11, 2022): 1352. http://dx.doi.org/10.3390/antiox11071352.
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Physalis peruviana-derived physapruin A (PHA) is a potent compound that selectively generates reactive oxygen species (ROS) and induces cancer cell death. Autophagy, a cellular self-clearance pathway, can be induced by ROS and plays a dual role in cancer cell death. However, the role of autophagy in PHA-treated cancer cells is not understood. Our study initially showed that autophagy inhibitors such as bafilomycin A1 enhanced the cytotoxic effects of PHA in breast cancer cell lines, including MCF7 and MDA-MB-231. PHA treatment decreased the p62 protein level and increased LC3-II flux. PHA increased the fluorescence intensity of DAPGreen and DALGreen, which are used to reflect the formation of autophagosome/autolysosome and autolysosome, respectively. ROS scavenger N-acetylcysteine (NAC) decreased PHA-elevated autophagy activity, implying that PHA-induced ROS may be required for autophagy induction in breast cancer cells. Moreover, the autophagy inhibitor increased ROS levels and enhanced PHA-elevated ROS levels, while NAC scavenges the produced ROS resulting from PHA and autophagy inhibitor. In addition, the autophagy inhibitor elevated the PHA-induced proportion of annexin V/7-aminoactinmycin D and cleavage of caspase-3/8/9 and poly (ADP-ribose) polymerase. In contrast, NAC and apoptosis inhibitor Z-VAD-FMK blocked the proportion of annexin V/7-aminoactinmycin D and the activation of caspases. Taken together, PHA induced ROS to promote autophagy, which might play an antioxidant and anti-apoptotic role in breast cancer cells.
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Ji, Xun, Omar M. Khdour, and Sidney M. Hecht. "Multifunctional radical quenchers as potential therapeutic agents for the treatment of mitochondrial dysfunction." Future Medicinal Chemistry 11, no. 13 (July 2019): 1605–24. http://dx.doi.org/10.4155/fmc-2018-0481.
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Mitochondrial dysfunction is associated with a wide range of human diseases, including neurodegenerative diseases, and is believed to cause or contribute to the etiology of these diseases. These disorders are frequently associated with increased levels of reactive oxygen species. One of the design strategies for therapeutic intervention involves the development of novel small molecules containing redox cores, which can scavenge reactive oxygen radicals and selectively block oxidative damage to the mitochondria. Presently, we describe recent research dealing with multifunctional radical quenchers as antioxidants able to scavenge reactive oxygen radicals. The review encompasses ubiquinone and tocopherol analogs, as well as novel pyri(mi)dinol derivatives, and their ability to function as protective agents in cellular models of mitochondrial diseases.
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Herb, Marc, and Michael Schramm. "Functions of ROS in Macrophages and Antimicrobial Immunity." Antioxidants 10, no. 2 (February 19, 2021): 313. http://dx.doi.org/10.3390/antiox10020313.
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Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors.
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Gopalakrishnan, Anusha M., and Nirbhay Kumar. "Antimalarial Action of Artesunate Involves DNA Damage Mediated by Reactive Oxygen Species." Antimicrobial Agents and Chemotherapy 59, no. 1 (October 27, 2014): 317–25. http://dx.doi.org/10.1128/aac.03663-14.
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ABSTRACTArtemisinin-based combination therapy (ACT) is the recommended first-line treatment forPlasmodium falciparummalaria. It has been suggested that the cytotoxic effect of artemisinin is mediated by free radicals followed by the alkylation ofP. falciparumproteins. The endoperoxide bridge, the active moiety of artemisinin derivatives, is cleaved in the presence of ferrous iron, generating reactive oxygen species (ROS) and other free radicals. However, the emergence of resistance to artemisinin inP. falciparumunderscores the need for new insights into the molecular mechanisms of antimalarial activity of artemisinin. Here we show that artesunate (ART) induces DNA double-strand breaks inP. falciparumin a physiologically relevant dose- and time-dependent manner. DNA damage induced by ART was accompanied by an increase in the intracellular ROS level in the parasites. Mannitol, a ROS scavenger, reversed the cytotoxic effect of ART and reduced DNA damage, and modulation of glutathione (GSH) levels was found to impact ROS and DNA damage induced by ART. Accumulation of ROS, increased DNA damage, and the resulting antiparasite effect suggest a causal relationship between ROS, DNA damage, and parasite death. Finally, we also show that ART-induced ROS production involves a potential role for NADPH oxidase, an enzyme involved in the production of superoxide anions. Our results withP. falciparumprovide novel insights into previously unknown molecular mechanisms underlying the antimalarial activity of artemisinin derivatives and may help in the design of next-generation antimalarial drugs against the most virulentPlasmodiumspecies.
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Lee, Kwan Yeop, Kyungsoon Chung, and Jin Mo Chung. "Involvement of Reactive Oxygen Species in Long-Term Potentiation in the Spinal Cord Dorsal Horn." Journal of Neurophysiology 103, no. 1 (January 2010): 382–91. http://dx.doi.org/10.1152/jn.90906.2008.
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Recent studies suggest that reactive oxygen species (ROS) are functional messenger molecules in central sensitization, an underlying mechanism of persistent pain. Because spinal cord long-term potentiation (LTP) is the electrophysiological basis of central sensitization, this study investigates the effects of the increased or decreased spinal ROS levels on spinal cord LTP. Spinal cord LTP is induced by either brief, high-frequency stimulation (HFS) of a dorsal root at C-fiber intensity or superfusion of a ROS donor, tert-butyl hydroperoxide (t-BOOH), onto rat spinal cord slice preparations. Field excitatory postsynaptic potentials (fEPSPs) evoked by dorsal root stimulations with either Aβ- or C-fiber intensity are recorded from the superficial dorsal horn. HFS significantly increases the slope of both Aβ- and C-fiber evoked fEPSPs, thus suggesting LTP development. The induction, not the maintenance, of HFS-induced LTP is blocked by a N-methyl-d-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonopentanoic acid (d-AP5). Both the induction and maintenance of LTP of Aβ-fiber-evoked fEPSPs are inhibited by a ROS scavenger, either N-tert-butyl-α-phenylnitrone or 4-hydroxy-2,2,6,6-tetramethylpiperidine- N-oxyl. A ROS donor, t-BOOH-induced LTP is inhibited by N-tert-butyl-α-phenylnitrone but not by d-AP5. Furthermore, HFS-induced LTP and t-BOOH-induced LTP occlude each other. The data suggest that elevated ROS is a downstream event of NMDA receptor activation and an essential step for potentiation of synaptic excitability in the spinal dorsal horn.
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Axelsson, Josefin, Anna Rippe, Kristinn Sverrisson, and Bengt Rippe. "Scavengers of reactive oxygen species, paracalcitol, RhoA, and Rac-1 inhibitors and tacrolimus inhibit angiotensin II-induced actions on glomerular permeability." American Journal of Physiology-Renal Physiology 305, no. 3 (August 1, 2013): F237—F243. http://dx.doi.org/10.1152/ajprenal.00154.2013.
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Systemic infusions of ANG II rapidly induce large, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor(s), ANG II generates reactive oxygen species (ROS) and produces Ca2+ influx into cells, leading to activation of a plethora of signaling cascades, including, e.g., calcineurin and small GTPases, such as Rac-1 and RhoA. In the present study we sought to interact with some of these cascades to test potential novel antiproteinuric agents. In anesthetized Wistar rats, the left urether was cannulated for urine collection, and blood access was achieved. Rats were infused with ANG II (16 ng·kg−1·min−1) alone, or together with the ROS scavengers tempol or dimethylthiourea (DMTU) or the D-vitamin analog paracalcitol, the RhoA-kinase inhibitor Y-27632, the Rac-1 inhibitor NSC-23766, or the calcineurin inhibitor tacrolimus. FITC-Ficoll-70/400 (mol.radius 10–80 Å) and 51Cr-EDTA were infused throughout the experiment. Plasma and urine samples were taken during baseline and at 5 and 15 min after the start of the infusions and analyzed by high-performance size-exclusion chromatography for determination of glomerular sieving coefficients (θ) for Ficoll10–80Å. ANG II infusion into rats caused marked increases in glomerular permeability to large Ficoll molecules (Ficoll50–80Å), which were abrogated by the ROS scavenger tempol and partly by DMTU. Paracalcitol, RhoA, and Rac-1 inhibition, and, to some extent tacrolimus, but not prostacyclin, could also inhibit the glomerular permeability actions of ANG II. Our data suggest that cellular ROS generation and active Ca2+ signaling are involved in ANG II-induced increases in glomerular permeability.
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Moustafa-Farag, Mohamed, Amr Elkelish, Mohamed Dafea, Mumtaz Khan, Marino B. Arnao, Magdi T. Abdelhamid, Aziz Abu El-Ezz, et al. "Role of Melatonin in Plant Tolerance to Soil Stressors: Salinity, pH and Heavy Metals." Molecules 25, no. 22 (November 17, 2020): 5359. http://dx.doi.org/10.3390/molecules25225359.
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Melatonin (MT) is a pleiotropic molecule with diverse and numerous actions both in plants and animals. In plants, MT acts as an excellent promotor of tolerance against abiotic stress situations such as drought, cold, heat, salinity, and chemical pollutants. In all these situations, MT has a stimulating effect on plants, fomenting many changes in biochemical processes and stress-related gene expression. Melatonin plays vital roles as an antioxidant and can work as a free radical scavenger to protect plants from oxidative stress by stabilization cell redox status; however, MT can alleviate the toxic oxygen and nitrogen species. Beyond this, MT stimulates the antioxidant enzymes and augments antioxidants, as well as activates the ascorbate–glutathione (AsA–GSH) cycle to scavenge excess reactive oxygen species (ROS). In this review, we examine the recent data on the capacity of MT to alleviate the effects of common abiotic soil stressors, such as salinity, alkalinity, acidity, and the presence of heavy metals, reinforcing the general metabolism of plants and counteracting harmful agents. An exhaustive analysis of the latest advances in this regard is presented, and possible future applications of MT are discussed.
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Simeonova, P. P., W. Toriumi, C. Kommineni, M. Erkan, A. E. Munson, W. N. Rom, and M. I. Luster. "Molecular regulation of IL-6 activation by asbestos in lung epithelial cells: role of reactive oxygen species." Journal of Immunology 159, no. 8 (October 15, 1997): 3921–28. http://dx.doi.org/10.4049/jimmunol.159.8.3921.
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Abstract IL-6 has been characterized as a pleiotropic cytokine with multiple biologic activities, but its induction and role in asbestos diseases have not been studied. Asbestos fibers were found to stimulate IL-6 expression and secretion in pulmonary type II-like epithelial A549 cells as well as in normal human bronchial epithelial cells. IL-6 induction was dependent on the intracellular redox-oxidative state, since intracellular hydroxyl scavengers and N-acetylcysteine, a precursor of glutathione, abrogated IL-6 secretion by asbestos or H2O2. IL-6 induction paralleled increased DNA binding activity to the nuclear factor-kappa B (NF-kappa B)- and NF-IL-6-recognized sites in the IL-6 promoter. The NF-kappa B and NF-IL-6 DNA binding proteins were immunochemically characterized as a heterodimer p65/p50 and a homodimer C/EBP beta, respectively. Stimulation of DNA binding activity to the NF-kappa B and NF-IL-6 binding sites of the IL-6 promoter by asbestos or H2O2 were inhibited by tetramethylthiourea, a hydroxyl radical scavenger. The role of local IL-6 production in the pathophysiologic processes of fiber-induced lung disorders was examined. Although less active than fibroblast growth factor, human rIL-6 also stimulated lung fibroblast growth, as evidenced by increased [3H]thymidine incorporation. Furthermore, elevated IL-6 levels were found in bronchoalveolar lavage fluids from patients diagnosed with lung fibrosis and work-related histories of long term asbestos exposure. Taken together, the results suggest that asbestos-induced oxidative stress is involved in the activation of NF-kappa B and NF-IL-6 transcription factors, which recognize the IL-6 promoter. The resulting increase in IL-6 expression may be involved in both inflammatory and fibrotic processes in the lung.
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Kataria, Tejinder, Deepak Gupta, Sasikumar Sambasivam, Nisha T. Vishnu, Shikha Goyal, Shyam Singh Bisht, Trinanjan Basu, Ashu Abhishek, Kushal Narang, and Susovan Banerjee. "Is wheat germ grass detrimental during radiotherapy?: a hypothesis." Journal of Radiotherapy in Practice 15, no. 3 (May 2, 2016): 296–302. http://dx.doi.org/10.1017/s1460396916000200.
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AbstractBackgroundAntioxidant therapies to control oxidative damage have already attracted worldwide attention in recent years. Extensive studies on phytochemicals in cell culture system and animal models have provided a wealth of information on the mechanism by which such nutraceuticals show their beneficial effect. Nutraceuticals include plant-derived factors (phytochemicals) and factors derived from animal sources as well as from microbial sources. The activities of nutraceuticals are broad and include antioxidation, modulation of enzyme activity and modification of natural hormonal activity (agonist or antagonist) to act as a precursor for one or more beneficial molecules. Antioxidants scavenge free radicals that cause cell damage. Antioxidant consumption during radiotherapy and its effects are still controversial. Some studies suggest that antioxidant supplementation during chemotherapy or radiotherapy may be beneficial and some, harmful. Wheat grass is rich in superoxide dismutase, an antioxidant enzyme. Radiotherapy causes tumour cell kill via activation of reactive oxygen species, specifically by the hydroxyl radical and needs the reactive species for effective tumour control. Wheat grass which is rich in free radical scavengers can interfere with reactive oxygen species generated by radiation for tumour cell kill and can be detrimental to the therapy per se.PurposeTo hypothesise if the antioxidant properties of wheat grass could influence tumour activity, the effects of radiation therapy on tumour cells can be nullified when wheat grass is taken during radiotherapy.
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Kavčič, Nežka, Katarina Pegan, Peter Vandenabeele, and Boris Turk. "Comparative study of the differential cell death protecting effect of various ROS scavengers." Biological Chemistry 400, no. 2 (January 28, 2019): 149–60. http://dx.doi.org/10.1515/hsz-2017-0317.
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AbstractOxidative stress has for a long time been associated with cell death, especially classical necrosis, however, its role in other cell death pathways is less clear. Here, we evaluated in a comparative way, the effect of four different reactive oxygen species (ROS) scavengers, N-acetyl-L-cysteine (NAC), α-tocopherol and two superoxide dismutase mimetics, n(III)tetrakis(4-benzoic acid)porphyrin chloride, and 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol), in four different cell death models, including menadione-triggered necrosis, staurosporine-induced apoptosis and tumor necrosis factor (TNF)-induced apoptosis and necroptosis. While menadione-triggered necrosis was completely prevented by the classical ROS scavenger NAC and to a substantial amount by the other scavengers, ROS targeting was found to have a marginal effect on the other cell death modalities investigated. Despite its side-effects at higher concentrations, Tempol was able to substantially prevent TNF-induced apoptosis and to a somewhat lesser extent TNF-induced necroptosis. However, this seems to be separated from its ROS-scavenging function.
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Sverrisson, Kristinn, Josefin Axelsson, Anna Rippe, Daniel Asgeirsson, and Bengt Rippe. "Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo." American Journal of Physiology-Renal Physiology 309, no. 9 (November 1, 2015): F800—F806. http://dx.doi.org/10.1152/ajprenal.00111.2015.
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This study was performed to investigate the immediate actions of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anesthetized rats, blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused intravenously with either IL-1β (0.4 and 2 μg·kg−1·h−1), TNF-α (0.4 and 2 μg·kg−1·h−1), or IL-6 (4 and 8 μg·kg−1·h−1), together with polydisperse FITC-Ficoll-70/400 and inulin for 1 h. Plasma and urine samples were analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ). The glomerular filtration rate (GFR) was also assessed (51Cr-EDTA). In separate experiments, the superoxide scavenger tempol (30 mg·kg−1·h−1) was given before and during cytokine infusions. IL-1β and TNF-α caused rapid, partly reversible increases in glomerular permeability to large molecules (Ficoll50–80Å), peaking at 5–30 min, while IL-6 caused a more gradual increase in permeability, leveling off at 60 min. Tempol almost completely abrogated the glomerular permeability effects of the cytokines infused. In conclusion IL-1β, TNF-α, and IL-6, when infused systemically, caused immediate and partly reversible increases in glomerular permeability, which could be inhibited by the superoxide scavenger tempol, suggesting an important role of ROS in acute cytokine-induced permeability changes in the GFB.
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Zandi, Peiman, and Ewald Schnug. "Reactive Oxygen Species, Antioxidant Responses and Implications from a Microbial Modulation Perspective." Biology 11, no. 2 (January 18, 2022): 155. http://dx.doi.org/10.3390/biology11020155.
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Plants are exposed to various environmental stresses in their lifespan that threaten their survival. Reactive oxygen species (ROS), the byproducts of aerobic metabolism, are essential signalling molecules in regulating multiple plant developmental processes as well as in reinforcing plant tolerance to biotic and abiotic stimuli. However, intensified environmental challenges such as salinity, drought, UV irradiation, and heavy metals usually interfere with natural ROS metabolism and homeostasis, thus aggravating ROS generation excessively and ultimately resulting in oxidative stress. Cellular damage is confined to the degradation of biomolecular structures, including carbohydrates, proteins, lipids, pigments, and DNA. The nature of the double-edged function of ROS as a secondary messenger or harmful oxidant has been attributed to the degree of existing balance between cellular ROS production and ROS removal machinery. The activities of enzyme-based antioxidants, catalase (CAT, EC 1.11.1.6), monodehydroascorbate reductase (MDHAR, E.C.1.6.5.4), dehydroascorbate reductase (DHAR, EC 1.8.5.1), superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), glutathione reductase (GR, EC 1.6.4.2), and guaiacol peroxidase (GPX, EC 1.11.1.7); and non-enzyme based antioxidant molecules, ascorbate (AA), glutathione (GSH), carotenoids, α-tocopherol, prolines, flavonoids, and phenolics, are indeed parts of the defensive strategies developed by plants to scavenge excess ROS and to maintain cellular redox homeostasis during oxidative stress. This review briefly summarises current knowledge on enzymatic and non-enzymatic antioxidant machinery in plants. Moreover, additional information about the beneficial impact of the microbiome on countering abiotic/biotic stresses in association with roots and plant tissues has also been provided.
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Tai, Ping, and Mario Ascoli. "Reactive Oxygen Species (ROS) Play a Critical Role in the cAMP-Induced Activation of Ras and the Phosphorylation of ERK1/2 in Leydig Cells." Molecular Endocrinology 25, no. 5 (May 1, 2011): 885–93. http://dx.doi.org/10.1210/me.2010-0489.
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Abstract Activation of the LH receptor (LHR) in Leydig cells results in the phosphorylation of ERK1/2 by cAMP-dependent and cAMP-independent pathways. Here we examine the mechanisms by which cAMP stimulates ERK1/2 phosphorylation. We show that the stimulation of steroidogenesis is not necessary or sufficient to stimulate the phosphorylation of ERK1/2 but that other cAMP-dependent mitochondrial functions are involved. Using MA-10 cells as a model, we showed that cAMP analogs increase reactive oxygen species (ROS) formation and that an uncoupler of oxidative phosphorylation and a ROS scavenger prevent this increase. These two compounds also inhibit the increase in ERK1/2 phosphorylation provoked by cAMP analogs, thus suggesting that the cAMP-induced phosphorylation of ERK1/2 is mediated by mitochondrial ROS. In agreement with this hypothesis we also show that a reduction in glutathione levels, which alters the redox state of MA-10 cells, potentiates the effect of cAMP on ERK1/2 phosphorylation. Measurements of the dephosphorylation of ERK and the activation of Ras showed that the ROS scavenger prevents the cAMP-provoked activation of Ras and that cAMP, with or without a ROS scavenger, has little or no effect on the dephosphorylation of ERK. Lastly, we show that the uncoupler of oxidative phosphorylation and the ROS scavenger also prevent the ability of cAMP analogs to increase ERK1/2 phosphorylation in primary cultures of mouse Leydig cells. We conclude that, in Leydig cells, cAMP enhances the phosphorylation of ERK1/2 via a mitochondria-derived, ROS-dependent activation of Ras.
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Sun, Lei, Tongsheng Chen, Xiaoping Wang, Yun Chen, and Xunbin Wei. "Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells." Evidence-Based Complementary and Alternative Medicine 2011 (2011): 1–12. http://dx.doi.org/10.1093/ecam/nep082.
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Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidantN-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.
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Li, Xiaoyan, Jinren Liu, Yueming Wu, Lingge Gao, Yan Ma, Guimin Xu, Guoqiang Li, et al. "Decolorization effect and related mechanism of atmospheric pressure plasma jet on Eriochrome Black T." Water Science and Technology 79, no. 6 (March 15, 2019): 1184–94. http://dx.doi.org/10.2166/wst.2019.120.
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Abstract In this study, Eriochrome Black T (EBT) in water was decolorized by means of argon atmospheric pressure plasma jet (APPJ), which showed great decolorization performance. The results showed that the relatively high decolorization rate (approximately 80%) was obtained after plasma treatment for 6 min. Changes to some reactive oxygen and nitrogen species (RONS) in the liquid phase were detected. The contents of peroxide, HO·, O2−·, and NO· in the plasma-treated EBT solution were much less than those in the activated water. The roles of H2O2 and HO· in the decolorization of EBT solution were explored by evaluating the effects of their scavengers, and by exploring the direct effect of H2O2. The results indicated that reactive oxygen species (ROS), especially HO· and O2−·, played significant roles in the decolorization of the EBT solution. Analysis of degradation by-products indicated that plasma discharge could destroy the azo bond first and gradually break the aromatic rings of EBT molecules into small molecular compounds.
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Gottlieb, Eyal, Matthew G. Vander Heiden, and Craig B. Thompson. "Bcl-xL Prevents the Initial Decrease in Mitochondrial Membrane Potential and Subsequent Reactive Oxygen Species Production during Tumor Necrosis Factor Alpha-Induced Apoptosis." Molecular and Cellular Biology 20, no. 15 (August 1, 2000): 5680–89. http://dx.doi.org/10.1128/mcb.20.15.5680-5689.2000.
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ABSTRACT The Bcl-2 family of proteins are involved in regulating the redox state of cells. However, the mode of action of Bcl-2 proteins remains unclear. This work analyzed the effects of Bcl-xL on the cellular redox state after treatment with tumor necrosis factor alpha (TNF-α) or exogenous oxidants. We show that in cells that undergo TNF-α-induced apoptosis, TNF-α induces a partial decrease in mitochondrial membrane potential (ΔΨ m ) followed by high levels of reactive oxygen species (ROS). ROS scavengers delay the progression of mitochondrial depolarization and apoptotic cell death. This indicates that ROS are important mediators of mitochondrial depolarization. However, ROS scavengers fail to prevent the initial TNF-α-induced decrease in ΔΨ m . In contrast, expression of Bcl-xL prevents both the initial decrease in ΔΨ m following TNF-α treatment and the subsequent induction of ROS. Bcl-xL itself does not act as a ROS scavenger. In addition, Bcl-xL does not block the initial decrease in ΔΨ m following treatment with the oxidant hydrogen peroxide. However, unlike control-transfected cells, Bcl-xL-expressing cells can recover their mitochondrial membrane potential following the initial drop in ΔΨ m induced by hydrogen peroxide. These data suggest that Bcl-xL plays a regulatory role in controlling the membrane potential of and ROS production by mitochondria rather than acting as a direct antioxidant.
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Emerling, Brooke M., Leonidas C. Platanias, Emma Black, Angel R. Nebreda, Roger J. Davis, and Navdeep S. Chandel. "Mitochondrial Reactive Oxygen Species Activation of p38 Mitogen-Activated Protein Kinase Is Required for Hypoxia Signaling." Molecular and Cellular Biology 25, no. 12 (June 15, 2005): 4853–62. http://dx.doi.org/10.1128/mcb.25.12.4853-4862.2005.
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ABSTRACT Mammalian cells have the ability to sense low oxygen levels (hypoxia). An adaptive response to hypoxia involves the induction of the transcription factor hypoxia-inducible factor 1 (HIF-1). The intracellular signaling pathways that regulate HIF-1 activation during hypoxia remain unknown. Here, we demonstrate that p38α − / − cells fail to activate HIF-1 under hypoxic conditions. Cells deficient in Mkk3 and Mkk6, the upstream regulators of p38α, also fail to activate HIF-1 under hypoxic conditions. The p38α − / − cells are able to activate HIF-1 in response to anoxia or iron chelators during normoxia. Furthermore, the hypoxic activation of p38α and HIF-1 was abolished by myxothiazol, a mitochondrial complex III inhibitor, and glutathione peroxidase 1 (GPX1), a scavenger of hydrogen peroxide. Thus, the activation of p38α and HIF-1 is dependent on the generation of mitochondrial reactive oxygen species. These results provide genetic evidence that p38 mitogen-activated protein kinase signaling is essential for HIF-1 activation.
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Sharipova, Guzel, Ruslan Ivanov, Dmitriy Veselov, Guzel Akhiyarova, Maria Shishova, Tatyana Nuzhnaya, and Guzel Kudoyarova. "Involvement of Reactive Oxygen Species in ABA-Induced Increase in Hydraulic Conductivity and Aquaporin Abundance." International Journal of Molecular Sciences 22, no. 17 (August 24, 2021): 9144. http://dx.doi.org/10.3390/ijms22179144.
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The role of reactive oxygen species (ROS) in ABA-induced increase in hydraulic conductivity was hypothesized to be dependent on an increase in aquaporin water channel (AQP) abundance. Single ABA application or its combination with ROS manipulators (ROS scavenger ascorbic acid and NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI)) were studied on detached roots of barley plants. We measured the osmotically driven flow rate of xylem sap and calculated root hydraulic conductivity. In parallel, immunolocalization of ABA and HvPIP2;2 AQPs was performed with corresponding specific antibodies. ABA treatment increased the flow rate of xylem, root hydraulic conductivity and immunostaining for ABA and HvPIP2;2, while the addition of antioxidants prevented the effects of this hormone. The obtained results confirmed the involvement of ROS in ABA effect on hydraulic conductivity, in particular, the importance of H2O2 production by ABA-treated plants for the effect of this hormone on AQP abundance.
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de Morais, Mariana Abrahão Bueno, Tatiana de Arruda Campos Brasil de Souza, and Mario Tyago Murakami. "Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the mitochondrial tryparedoxin peroxidase fromLeishmania braziliensis." Acta Crystallographica Section F Structural Biology and Crystallization Communications 69, no. 4 (March 28, 2013): 408–11. http://dx.doi.org/10.1107/s1744309113003989.
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Tryparedoxin peroxidase (TXNPx) is an essential constituent of the main enzymatic scavenger system for reactive oxygen species (ROS) in trypanosomatids. Genetic studies have demonstrated the importance of this system for the development and virulence of these parasites, representing a potential target for the discovery of new trypanocidal drugs. In this work, the mitochondrial TXNPx fromLeishmania braziliensiswas cloned, overexpressed, purified and crystallized. The crystals diffracted to 3.3 Å resolution and belonged to space groupP42212, with unit-cell parametersa=b= 131.8,c= 44.4 Å. These studies will contribute to a better understanding of the molecular mechanisms involved in ROS detoxification by trypanosomatids.
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Wang, Xiaohang, Hirosato Kanda, Takeshi Tsujino, Yoko Kogure, Feng Zhu, Satoshi Yamamoto, Taichi Sakaguchi, Koichi Noguchi, and Yi Dai. "Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model." International Journal of Molecular Sciences 23, no. 5 (March 4, 2022): 2820. http://dx.doi.org/10.3390/ijms23052820.
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Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30–40% patients continue to have angina after a successful PCI, thereby reducing patient satisfaction. The mechanisms underlying persistent angina after revascularisation therapy are still poorly understood; hence, the treatment or guideline for post-PCI angina remains unestablished. Thus, this study aimed to investigate the mechanisms underlying effort angina in animals following myocardial ischaemia-reperfusion (I/R) injury. Phosphorylated extracellular signal-regulated kinase (p-ERK), a marker for painful stimulation-induced neuronal activation, was used for the investigation. After a forced treadmill exercise (FTE), the number of p-ERK-expressing neurons increased in the superficial dorsal horn of the I/R model animals. Moreover, FTE evoked hydrogen peroxide (H2O2) production in the I/R-injured heart, inducing angina through TRPA1 activation on cardiac sensory fibres. Notably, the treatment of a TEMPOL, a reactive oxygen species scavenger, or TRPA1−/− mice successfully alleviated the FTE-induced p-ERK expression in the dorsal horn. The production of H2O2, a reactive oxygen species, through physical exercise contributes to angina development following I/R. Hence, our findings may be useful for understanding and treating angina following revascularisation therapy.
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Cucarull, Blanca, Anna Tutusaus, Tania Hernáez-Alsina, Pablo García de Frutos, María Reig, Anna Colell, Montserrat Marí, and Albert Morales. "Antioxidants Threaten Multikinase Inhibitor Efficacy against Liver Cancer by Blocking Mitochondrial Reactive Oxygen Species." Antioxidants 10, no. 9 (August 24, 2021): 1336. http://dx.doi.org/10.3390/antiox10091336.
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Sorafenib and regorafenib, multikinase inhibitors (MKIs) used as standard chemotherapeutic agents for hepatocellular carcinoma (HCC), generate reactive oxygen species (ROS) during cancer treatment. Antioxidant supplements are becoming popular additions to our diet, particularly glutathione derivatives and mitochondrial-directed compounds. To address their possible interference during HCC chemotherapy, we analyzed the effect of common antioxidants using hepatoma cell lines and tumor spheroids. In liver cancer cell lines, sorafenib and regorafenib induced mitochondrial ROS production and potent cell death after glutathione depletion. In contrast, cabozantinib only exhibited oxidative cell death in specific HCC cell lines. After sorafenib and regorafenib administration, antioxidants such as glutathione methyl ester and the superoxide scavenger MnTBAP decreased cell death and ROS production, precluding the MKI activity against hepatoma cells. Interestingly, sorafenib-induced mitochondrial damage caused PINK/Parkin-dependent mitophagy stimulation, altered by increased ROS production. Finally, in sorafenib-treated tumor spheroids, while ROS induction reduced tumor growth, antioxidant treatments favored tumor development. In conclusion, the anti-tumor activity of specific MKIs, such as regorafenib and sorafenib, is altered by the cellular redox status, suggesting that uncontrolled antioxidant intake during HCC treatment should be avoided or only endorsed to diminish chemotherapy-induced side effects, always under medical scrutiny.
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Vellosa, José Carlos Rebuglio, Najeh Maissar Khalil, Vânia Ortega Gutierres, Vânia Aparecida de Freitas Formenton Macedo dos Santos, Maysa Furlan, Iguatemy Lourenço Brunetti, and Olga Maria Mascarenhas de Faria Oliveira. "Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile." Brazilian Journal of Pharmaceutical Sciences 45, no. 1 (March 2009): 99–107. http://dx.doi.org/10.1590/s1984-82502009000100012.
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Reactive oxygen species (ROS) and free radical species have been implicated in initiating or accompanying many diseases in living organisms; there is thus, a continual need for antioxidants molecules to inactivate ROS/free radicals. Many studies of plants crude extracts have demonstrated free-radical scavenging and antioxidant action. Salacia species have long been used, in several countries, as traditional medicines against certain diseases and for their anti-inflammatory properties. In this study, Salacia campestris Walp (Hippocrateaceae) root bark ethanol extract (ScEtOH) was assessed for its ability to scavenge free radicals and reactive oxygen species; the results were expressed as percentage inhibition of the active species. ScEtOH was efficient against studied species: DPPH radical (obtained inhibition = 30%), ABTS•+ (IC50 = 1.8±0.8 μg/mL), HOCl (IC50 = 1.7 ± 0.1 μg/mL), O2•- (obtained inhibition = 32%), and NO• (obtained inhibition = 18 %). Peroxidase activity inhibition was evaluated through the guaiacol oxidation reaction catalyzed by hemin, HRP and myeloperoxidase (MPO); data showed that ScEtOH at 10 μg/mL led to 54 and 51% of inhibition, respectively, for the hemin and HRP systems. In the MPO system, ScEtOH promoted a 50% inhibition at 8.9 μg/mL, whereas quercetin, a powerful MPO inhibitor, inhibited this system at 1.35 μg/mL.
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Medina, L. F. C., P. F. Hertz, V. Stefani, J. A. P. Henriques, A. Zanotto-Filho, and A. Brandelli. "Aminonaphthoquinone induces oxidative stress inStaphylococcus aureus." Biochemistry and Cell Biology 84, no. 5 (October 2006): 720–27. http://dx.doi.org/10.1139/o06-087.
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The biological activity of 5-amino-8-hydroxy-1,4-naphthoquinone (ANQ) on Staphylococcus aureus was investigated in comparison with the unsubstituted 1,4-naphthoquinone (NQ). Complete inhibition of microbial growth was observed with ANQ and NQ at 50 and 10 µg/mL, respectively. The antibacterial effect of naphthoquinones decreased in the presence of sodium ascorbate, but the superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) was able to protect S. aureus only from the harmful effect of ANQ. Naphthoquinones blocked oxygen uptake and induced cyanide-insensitive oxygen consumption. When combining rotenone or salicylhydroxamic acid with ANQ or NQ, a slight decrease in respiratory activity was observed. Assays in the presence of naphthoquinones induced an increase of lipid peroxidation in S. aureus, as determined by thiobarbituric acid reactive substances. These results showed that 1,4-naphthoquinones effectively act as electron acceptors and induce an increase in reactive oxygen species that are toxic to S. aureus cells.
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Cembrowska-Lech, Danuta. "Tissue Printing and Dual Excitation Flow Cytometry for Oxidative Stress—New Tools for Reactive Oxygen Species Research in Seed Biology." International Journal of Molecular Sciences 21, no. 22 (November 17, 2020): 8656. http://dx.doi.org/10.3390/ijms21228656.
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The intracellular homeostasis of reactive oxygen species (ROS) and especially of superoxide anion and hydrogen peroxide participate in signaling cascades which dictate developmental processes and reactions to stresses. ROS are also biological molecules that play important roles in seed dormancy and germination. Because of their rapid reactivity, short half-life and low concentration, ROS are difficult to measure directly with high accuracy and precision. In presented work tissue printing method with image analysis and dual excitation flow cytometry (FCM) were developed for rapid detection and localization of O2•− and H2O2 in different part of seed. Tissue printing and FCM detection of ROS showed that germination of wild oat seeds was associated with the accumulation of O2•− and H2O2 in embryo (coleorhiza, radicle and scutellum), aleurone layer and coat. To verify if printing and FCM signals were specified, the detection of O2•− and H2O2 in seeds incubated in presence of O2•− generation inhibitor (DPI) or H2O2 scavenger (CAT) were examined. All results were a high level of agreement among the level of ROS derived from presented procedures with the ones created from spectrophotometric measured data. In view of the data obtained, tissue printing with image analysis and FCM are recommended as a simple and fast methods, which could help researchers to detection and level determination of ROS in the external and inner parts of the seeds.
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Rani, Alka, Khem Saini, Felix Bast, Sanjeet Mehariya, Shashi Bhatia, Roberto Lavecchia, and Antonio Zuorro. "Microorganisms: A Potential Source of Bioactive Molecules for Antioxidant Applications." Molecules 26, no. 4 (February 20, 2021): 1142. http://dx.doi.org/10.3390/molecules26041142.
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Oxidative stress originates from an elevated intracellular level of free oxygen radicals that cause lipid peroxidation, protein denaturation, DNA hydroxylation, and apoptosis, ultimately impairing cell viability. Antioxidants scavenge free radicals and reduce oxidative stress, which further helps to prevent cellular damage. Medicinal plants, fruits, and spices are the primary sources of antioxidants from time immemorial. In contrast to plants, microorganisms can be used as a source of antioxidants with the advantage of fast growth under controlled conditions. Further, microbe-based antioxidants are nontoxic, noncarcinogenic, and biodegradable as compared to synthetic antioxidants. The present review aims to summarize the current state of the research on the antioxidant activity of microorganisms including actinomycetes, bacteria, fungi, protozoa, microalgae, and yeast, which produce a variety of antioxidant compounds, i.e., carotenoids, polyphenols, vitamins, and sterol, etc. Special emphasis is given to the mechanisms and signaling pathways followed by antioxidants to scavenge Reactive Oxygen Species (ROS), especially for those antioxidant compounds that have been scarcely investigated so far.
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Sinha, Niharika, Prashanta Kumar Panda, Prajna Paramita Naik, Tapas K. Maiti, and Sujit K. Bhutia. "Abrus agglutinin targets cancer stem-like cells by eliminating self-renewal capacity accompanied with apoptosis in oral squamous cell carcinoma." Tumor Biology 39, no. 5 (May 2017): 101042831770163. http://dx.doi.org/10.1177/1010428317701634.
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The accumulating evidences show that Abrus agglutinin, a plant lectin, displays a broad range of anticancer activity including cancer-specific induction of apoptosis; however, the underlying molecular mechanism of Abrus agglutinin–induced oral cancer stem cell elimination remains elusive. Our data documented that Abrus agglutinin effectively downregulated the CD44+ expression with the increased CD44− population in different oral cancer cells. After 24-h Abrus agglutinin treatment, FaDu cells were quantified for orosphere formation in ultra-low attachment plates and data showed that Abrus agglutinin inhibited the number and size of orosphere in a dose-dependent manner in FaDu cells. Furthermore, Abrus agglutinin hindered the plasticity of FaDu orospheres as supported by reduced sphere formation and downregulated the self-renewal property via inhibition of Wnt-β-catenin signaling pathway. Introduction of LiCl, a glycogen synthase kinase 3β inhibitor, rescued the Abrus agglutinin–stimulated inhibition of β-catenin and phosphorylated glycogen synthase kinase 3β in FaDu cell–derived orospheres confirming importance of Wnt signaling in Abrus agglutinin–mediated inhibition of stemness. In this connection, our data showed that Abrus agglutinin restrained proliferation and induced apoptosis in FaDu-derived cancer stem cells in dose-dependent manner. Moreover, western blot data demonstrated that Abrus agglutinin increased the Bax/Bcl-2 ratio with activation of poly(adenosine diphosphate–ribose) polymerase and caspase-3 favoring apoptosis induction in orospheres. Abrus agglutinin induced reactive oxygen species accumulation in orospheres and pretreatment of N-acetyl cysteine, and a reactive oxygen species scavenger inhibited Abrus agglutinin–mediated caspase-3 activity and β-catenin expression indicating reactive oxygen species as a principal regulator of Wnt signaling and apoptosis. In conclusion, Abrus agglutinin has a potential role as an integrative therapeutic approach for combating oral cancer through targeting self-renewability of orospheres via reactive oxygen species–mediated apoptosis.
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Fukuhara, Kiyoshi, Ikuo Nakanishi, Kohei Imai, Mirei Mizuno, Ken-ichiro Matsumoto, and Akiko Ohno. "DTPA-Bound Planar Catechin with Potent Antioxidant Activity Triggered by Fe3+ Coordination." Antioxidants 12, no. 2 (January 18, 2023): 225. http://dx.doi.org/10.3390/antiox12020225.
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In diseases related to oxidative stress, accumulation of metal ions at the site of pathogenesis results in the generation of reactive oxygen species (ROS) through the reductive activation of oxygen molecules catalyzed by the metal ions. If these metals can be removed and the generated ROS can be strongly scavenged, such diseases can be prevented and treated. Planar catechins exhibit stronger radical scavenging activity than natural catechins and can efficiently scavenge hydroxyl radicals generated by the Fenton reaction without showing pro-oxidant effects, even in the presence of iron ions. Hence, in the current study, we designed a compound in which diethylenetriaminepentaacetic acid (DTPA), a metal chelator, was bound to a planar catechin with enhanced radical scavenging activity by immobilizing the steric structure of a natural catechin to be planar. This compound showed almost no radical scavenging activity due to intramolecular hydrogen bonding of DTPA with the planar catechins; however, when coordinated with Fe3+, it showed more potent radical scavenging activity than planar catechins. Owing to its potent antioxidant activity triggered by metal coordination and its inhibition of ROS generation by trapping metal ions, this compound might exert excellent preventive and therapeutic effects against oxidative stress-related diseases.
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D’Angelo, Gabriella, Roberto Chimenz, Russel J. Reiter, and Eloisa Gitto. "Use of Melatonin in Oxidative Stress Related Neonatal Diseases." Antioxidants 9, no. 6 (June 2, 2020): 477. http://dx.doi.org/10.3390/antiox9060477.
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Reactive oxygen species have a crucial role in the pathogenesis of perinatal diseases. Exposure to inflammation, infections, or high oxygen concentrations is frequent in preterm infants, who have high free iron levels that enhance toxic radical generation and diminish antioxidant defense. The peculiar susceptibility of newborns to oxidative stress supports the prophylactic use of melatonin in preventing or decreasing oxidative stress-mediated diseases. Melatonin, an effective direct free-radical scavenger, easily diffuses through biological membranes and exerts pleiotropic activity everywhere. Multiple investigations have assessed the effectiveness of melatonin to reduce the “oxygen radical diseases of newborn” including perinatal brain injury, sepsis, chronic lung disease (CLD), and necrotizing enterocolitis (NEC). Further studies are still awaited to test melatonin activity during perinatal period.
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Yang, S. G., H. J. Park, J. W. Kim, J. M. Jung, H. G. Jegal, I. S. Kim, P. S. Jeong, and D. B. Koo. "78 Mito-TEMPO, a Scavenger for Mitochondria-Derived Reactive Oxygen Species, Enhances Porcine Pre-Implantation Embryo Development." Reproduction, Fertility and Development 30, no. 1 (2018): 177. http://dx.doi.org/10.1071/rdv30n1ab78.
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The production of reactive oxygen species (ROS) from mitochondria contributes to redox signalling, mitochondrial functions, and apoptosis. However, the specific effects of mitochondria target superoxide (O2 •–) on porcine embryo development remain unclear. The objective of present study was to examine the differences of mitochondrial functions and dynamics in 2 subpopulations of porcine zygotes (G1 and G2), and to investigate the effects of Mito-TEMPO on porcine embryo development. Porcine embryos were visually classified in 2 groups [Grade (G)1: over 90%, and G2: below 90%] according to the lipid distribution at the zygote stage. The blastocyst development rate was greater in G1 than in G2 embryos (G1: 26.5 ± 5.9% v. G2: 16.2 ± 7.9%; P < 0.05). To evaluate blastocyst quality, we performed a 4′,6-diamidino-2-phenylindole (DAPI)-TUNEL assay. The proportion of TUNEL-positive cells was higher (P < 0.05) in G2 than G1 embryos. We measured superoxide production by MitoSOX staining as mitochondrial superoxide specific fluorescence dye by iRiSTM Digital Cell Image System (Logos Biosystems Inc., Gyeonggi-do, South Korea). Red fluorescence intensity of superoxide in G2 embryos significantly increased (P < 0.05) compared with that in G1. We investigated changes in mitochondrial functions using a Mitotracker JC-1 mitochondrial membrane potential assay kit (Thermo Fisher Scientific, Waltham, MA, USA) and ATP determination kit, respectively. Mitochondria membrane potential and ATP production were lower (P < 0.05) in G2 embryos than in G1 embryos. To confirm the protein levels of mitochondria fission protein DRP1, we performed Western blot analysis (per 40 embryos). Phosphorylation DRP1-Ser616 was increased (P < 0.05) in G1 embryos at cleavage stage compared with that in zygote, but not significantly different in G2 embryos. Thus, G2 embryos showed low development rate until blastocyst via mitochondrial dysfunction, increase in fission protein expression and mitochondrial aggregation according to the elevation of mito-ROS. Subsequently, the effect of the adding superoxide scavenger Mito-TEMPO was investigated in G2 embryos. Blastocyst formation (G2+MitoTempo: 28.8 ± 4.0% v. G2: 19.1 ± 5.1%; P < 0.05) and mitochondrial aggregation were recovered by mito-ROS reduction mediated by Mito-TEMPO. Our observations demonstrated that regulation of superoxide in mitochondria is important in pre-implantation development of porcine embryos. This work was supported by grants from the Next-Generation BioGreen 21 Program (PJ01117604) and the Bio-industry Technology Development Program (316037-04-2-HD020) through the Rural Development Administration and the Ministry of Agriculture, Food and Rural Affairs, Republic of Korea.
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Cha, Sun Joo, and Kiyoung Kim. "Effects of the Edaravone, a Drug Approved for the Treatment of Amyotrophic Lateral Sclerosis, on Mitochondrial Function and Neuroprotection." Antioxidants 11, no. 2 (January 20, 2022): 195. http://dx.doi.org/10.3390/antiox11020195.
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Edaravone, the first known free radical scavenger, has demonstrated cellular protective properties in animals and humans. Owing to its antioxidant activity, edaravone modulates oxidative damage in various diseases, especially neurodegenerative diseases. In 2015, edaravone was approved in Japan to treat amyotrophic lateral sclerosis. The distinguishing pathogenic features of neurodegenerative diseases include high reactive oxygen species levels and mitochondrial dysfunction. However, the correlation between mitochondria and edaravone has not been elucidated. This review highlights recent studies on novel therapeutic perspectives of edaravone in terms of its effect on oxidative stress and mitochondrial function.
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Yoshida, Kozue, Keita Kirito, Kenneth Kaushansky, and Norio Komatsu. "Thrombopoietin (TPO) Regulates HIF-1α Level through Generation of Mitochondrial Reactive Oxygen Species (ROS)." Blood 106, no. 11 (November 16, 2005): 3145. http://dx.doi.org/10.1182/blood.v106.11.3145.3145.
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Abstract Hypoxia inducible factor (HIF)-1 is a master transcriptional regulator for adaptation of cells to hypoxia. In addition to hypoxic responses, HIF-1 also plays an important role in the development of hematopoietic stem cells. Genetic deletion of β subunit of HIF-1 causes impairment of hematopoiesis. Culture of hematopoietic stem cells under hypoxic condition induces elevation of HIF-1α , another subunit of HIF-1, and subsequently enhances the growth of these cells. In our previous work we found that thrombopoietin (TPO), an important and non-redundant cytokine required for normal stem cell development, induces HIF-1α elevation in the TPO-dependent human leukemic cell line UT-7/TPO and in Sca-1+/c-kit+/Gr-1- cells (Kirito, K. et.al. Blood 2005). Under normoxic conditions HIF-1α is hydroxylated on proline residues by prolyl hydroxylase (PHD), which leads to its recognition by the von Hippel-Lindau tumor suppressor protein (pVHL), leading to degradation of HIF-1α . Hypoxia inhibits PHD function, blocking ubiquitination of HIF-1α , stabilizing the protein. We found that TPO controls stability of HIF-1α even under normoxic conditions. However, the mechanism by which TPO controls the stability of the protein remains unclear. Recently, several groups have reported that mitochondrial ROS play crucial roles in stabilization of HIF-1α in response to hypoxia. Disruption of mitochondrial function, either by interfering RNA against complex III of the mitochondrial electron transport chain or genetic elimination of cytochrome c, completely abolished the hypoxia-induced HIF-1α response. Based on these findings we hypothesized that ROS might be involved in TPO-induced HIF-1α elevation. To examine our hypothesis, we first tested whether TPO induced ROS production in UT-7/TPO cells using 2′, 7′-dichlorofluorescein diacetate, a redox sensitive fluorescence dye, and found that the hormone clearly induced ROS production in these cells. Next, we analyzed whether TPO-induced ROS generation is required for accumulation of HIF-1α . Pre-treatment of UT-7/TPO cells with the ROS scavenger catalase completely blocked HIF-1α elevation after TPO treatment. Furthermore, diphenylene iodinium (DPI), an inhibitor for ROS generating flavoenzymes including mitochondrial respiratory complexes, also inhibited the effects of TPO on HIF-1α levels. These results indicate that TPO induced HIF-1α activation is mediated by ROS production. To study the molecular pathway(s) by which TPO affects ROS, we tested the effects of ROS blockade on several known TPO-responsive signaling molecules; neither DPI nor catalase affected the activation of JAK2, STAT5, p38-MAPK or p42/p44-ERK induced by TPO, although AKT activation was blocked. Moreover, LY294002, an inhibitor of PI3-kinase and its activation of AKT also blocked of the HIF-1α response to TPO. Finally, inhibition of mitochondrial function in UT-7/TPO cells with rotenone or oligomycin also inhibited TPO-dependent accumulation of HIF-1α without affecting Jak2 activation. In conclusion, we found that TPO regulates HIF-1α levels through activation of ROS generation within mitochondrial respiratory complexes. We speculate that TPO mimics hypoxia by induction of ROS generation at mitochondria and subsequent elevation of HIF-1α , and regulates important genes for metabolisms and survival of hematopoietic stem cells.
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Bodega, Guillermo, Matilde Alique, Lourdes Bohórquez, Miriam Morán, Luis Magro, Lilian Puebla, Sergio Ciordia, María C. Mena, Elvira Arza, and Manuel R. Ramírez. "Young and Especially Senescent Endothelial Microvesicles Produce NADPH: The Fuel for Their Antioxidant Machinery." Oxidative Medicine and Cellular Longevity 2018 (2018): 1–12. http://dx.doi.org/10.1155/2018/3183794.
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In a previous study, we demonstrated that endothelial microvesicles (eMVs) have a well-developed enzymatic team involved in reactive oxygen species detoxification. In the present paper, we demonstrate that eMVs can synthesize the reducing power (NAD(P)H) that nourishes this enzymatic team, especially those eMVs derived from senescent human umbilical vein endothelial cells. Moreover, we have demonstrated that the molecules that nourish the enzymatic machinery involved in NAD(P)H synthesis are blood plasma metabolites: lactate, pyruvate, glucose, glycerol, and branched-chain amino acids. Drastic biochemical changes are observed in senescent eMVs to optimize the synthesis of reducing power. Mitochondrial activity is diminished and the glycolytic pathway is modified to increase the activity of the pentose phosphate pathway. Different dehydrogenases involved in NADPH synthesis are also increased. Functional experiments have demonstrated that eMVs can synthesize NADPH. In addition, the existence of NADPH in eMVs was confirmed by mass spectrometry. Multiphoton confocal microscopy images corroborate the synthesis of reducing power in eMVs. In conclusion, our present and previous results demonstrate that eMVs can act as autonomous reactive oxygen species scavengers: they use blood metabolites to synthesize the NADPH that fuels their antioxidant machinery. Moreover, senescent eMVs have a stronger reactive oxygen species scavenging capacity than young eMVs.
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Thuy, Le Thi Thanh, Hoang Hai, and Norifumi Kawada. "Role of cytoglobin, a novel radical scavenger, in stellate cell activation and hepatic fibrosis." Clinical and Molecular Hepatology 26, no. 3 (July 1, 2020): 280–93. http://dx.doi.org/10.3350/cmh.2020.0037.
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Cytoglobin (Cygb), a stellate cell-specific globin, has recently drawn attention due to its association with liver fibrosis. In the livers of both humans and rodents, Cygb is expressed only in stellate cells and can be utilized as a marker to distinguish stellate cells from hepatic fibroblast-derived myofibroblasts. Loss of Cygb accelerates liver fibrosis and cancer development in mouse models of chronic liver injury including diethylnitrosamine-induced hepatocellular carcinoma, bile duct ligation-induced cholestasis, thioacetamide-induced hepatic fibrosis, and choline-deficient L-amino acid-defined diet-induced non-alcoholic steatohepatitis. This review focuses on the history of research into the role of reactive oxygen species and nitrogen species in liver fibrosis and discusses the current perception of Cygb as a novel radical scavenger with an emphasis on its role in hepatic stellate cell activation and fibrosis.