scholarly journals NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation

2007 ◽  
Vol 406 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Lena Serrander ◽  
Laetitia Cartier ◽  
Karen Bedard ◽  
Botond Banfi ◽  
Bernard Lardy ◽  
...  
Keyword(s):  
Physiological Function ◽  
Close Correlation ◽  
Ros Generation ◽  
Mrna Levels ◽  
Oxygen Species ◽  
Pharmacological Profile ◽  
Nadph Oxidases ◽  
Activation Mechanisms ◽  
Tetracycline Induction ◽  
Ros Reactive Oxygen Species

NOX4 is an enigmatic member of the NOX (NADPH oxidase) family of ROS (reactive oxygen species)-generating NADPH oxidases. NOX4 has a wide tissue distribution, but the physiological function and activation mechanisms are largely unknown, and its pharmacology is poorly understood. We have generated cell lines expressing NOX4 upon tetracycline induction. Tetracycline induced a rapid increase in NOX4 mRNA (1 h) followed closely (2 h) by a release of ROS. Upon tetracycline withdrawal, NOX4 mRNA levels and ROS release decreased rapidly (<24 h). In membrane preparations, NOX4 activity was selective for NADPH over NADH and did not require the addition of cytosol. The pharmacological profile of NOX4 was distinct from other NOX isoforms: DPI (diphenyleneiodonium chloride) and thioridazine inhibited the enzyme efficiently, whereas apocynin and gliotoxin did not (IC50>100 μM). The pattern of NOX4-dependent ROS generation was unique: (i) ROS release upon NOX4 induction was spontaneous without need for a stimulus, and (ii) the type of ROS released from NOX4-expressing cells was H2O2, whereas superoxide (O2−) was almost undetectable. Probes that allow detection of intracellular O2− generation yielded differential results: DHE (dihydroethidium) fluorescence and ACP (1-acetoxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine) ESR measurements did not detect any NOX4 signal, whereas a robust signal was observed with NBT. Thus NOX4 probably generates O2− within an intracellular compartment that is accessible to NBT (Nitro Blue Tetrazolium), but not to DHE or ACP. In conclusion, NOX4 has a distinct pharmacology and pattern of ROS generation. The close correlation between NOX4 mRNA and ROS generation might hint towards a function as an inducible NOX isoform.

An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations

2007 ◽  
Vol 292 (1) ◽  
pp. R18-R36 ◽  
Author(s):  
Kevin C. Kregel ◽  
Hannah J. Zhang
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Physiological Function ◽  
Ros Generation ◽  
Oxygen Species ◽  
Stress Theory ◽  
Complex Process ◽  
Potential Impact ◽  
Critical Aspects

Aging is an inherently complex process that is manifested within an organism at genetic, molecular, cellular, organ, and system levels. Although the fundamental mechanisms are still poorly understood, a growing body of evidence points toward reactive oxygen species (ROS) as one of the primary determinants of aging. The “oxidative stress theory” holds that a progressive and irreversible accumulation of oxidative damage caused by ROS impacts on critical aspects of the aging process and contributes to impaired physiological function, increased incidence of disease, and a reduction in life span. While compelling correlative data have been generated to support the oxidative stress theory, a direct cause-and-effect relationship between the accumulation of oxidatively mediated damage and aging has not been strongly established. The goal of this minireview is to broadly describe mechanisms of in vivo ROS generation, examine the potential impact of ROS and oxidative damage on cellular function, and evaluate how these responses change with aging in physiologically relevant situations. In addition, the mounting genetic evidence that links oxidative stress to aging is discussed, as well as the potential challenges and benefits associated with the development of antiaging interventions and therapies.

Novel Nox homologues in the vasculature: focusing on Nox4 and Nox5

2010 ◽  
Vol 120 (4) ◽  
pp. 131-141 ◽  
Author(s):  
Augusto C. Montezano ◽  
Dylan Burger ◽  
Graziela S. Ceravolo ◽  
Hiba Yusuf ◽  
Maria Montero ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tissue Distribution ◽  
The Other ◽  
Oxygen Species ◽  
Biological Functions ◽  
Renal Cells ◽  
Nadph Oxidases ◽  
Cellular Compartments ◽  
Ros Reactive Oxygen Species

The Noxes (NADPH oxidases) are a family of ROS (reactive oxygen species)-generating enzymes. Of the seven family members, four have been identified as important sources of ROS in the vasculature: Nox1, Nox2, Nox4 and Nox5. Although Nox isoforms can be influenced by the same stimulus and co-localize in cellular compartments, their tissue distribution, subcellular regulation, requirement for cofactors and NADPH oxidase subunits and ability to generate specific ROS differ, which may help to understand the multiplicity of biological functions of these oxidases. Nox4 and Nox5 are the newest isoforms identified in the vasculature. Nox4 is the major isoform expressed in renal cells and appear to produce primarily H2O2. The Nox5 isoform produces ROS in response to increased levels of intracellular Ca2+ and does not require the other NADPH oxidase subunits for its activation. The present review focuses on these unique Noxes, Nox4 and Nox5, and provides novel concepts related to the regulation and interaction in the vasculature, and discusses new potential roles for these isoforms in vascular biology.

Abstract 196: NADPH Oxidase Isoforms NOX1 and NOX2 Differentially Regulate GPVI- and Non-GPVI-Dependent ROS Generation and Platelet Activation

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Huzoor Akbar ◽  
Xin Duan ◽  
Saima Saleem ◽  
Ashley K Davis ◽  
Yi Zheng
Keyword(s):  
Reactive Oxygen Species ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Myosin Light Chain ◽  
Human Platelets ◽  
Ros Generation ◽  
Oxygen Species ◽  
Nadph Oxidases ◽  
Atp Secretion ◽  
Molecule Inhibitor

Reactive oxygen species (ROS) play an important role in platelet activation. Although diverse biochemical reactions contribute to ROS generation, NADPH oxidases (NOX) have emerged as critical sources of agonist induced ROS generation in platelets. Platelets express two NOX isoforms, NOX1 and NOX2. In this study we investigated the effects of ML171 (0.1-1 μM), a selective NOX1 inhibitor (ACS Chem Biol. 5, 981-993, 2010), and Phox-I (1-10 μM), a rationally designed small molecule inhibitor of NOX2 (Chem. Biol. 19, 699-710, 2012), to define the roles of NOX1 and NOX2 in ROS-mediated platelet activation by diverse agonists. A two-minute pre-incubation of washed human platelets with ML171 or Phox-I inhibited CRP, a GPVI agonist, induced ROS generation, ATP secretion and platelet aggregation. In contrast, only platelets treated with Phox-I, but not ML171, inhibited CRP induced binding of PAC-1 to platelets and expression of P-selectin. Treatment of platelets with Phox-I, but not ML-171, inhibited thrombin or U46619, a stable analog of TXA 2 , induced ROS generation, P-selectin expression, ATP secretion and aggregation. Both Phox-I and ML171 inhibited CRP induced phosphorylation of myosin light chain (MLC) and Akt. However, only Phox-I inhibited thrombin induced phosphorylation of MLC or Akt. Treatment of platelets with Phox-I or ML171 only minimally or partially inhibited CRP induced phosphorylation of p38-MAPK or ERK. In other experiments, incubation of platelets with varying concentrations of both ML171 and Phox-I did not exhibit additive effect on CRP induced ROS generation. These results imply that ROS generation by these NOX isoforms may be sequential. These data suggest that NOX1 is specifically involved in GPVI mediated, whereas NOX2 is involved in GPVI- and non-GPVI-dependent, signals in ROS generation and platelet activation.

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.

scholarly journals CBIO-07. CELL DEATH INDUCED BY AN OSCILLATING MAGNETIC FIELD IN PATIENT DERIVED GLIOBLASTOMA CELLS IS MEDIATED BY REACTIVE OXYGEN SPECIES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
Shashank Hambarde ◽  
Martyn Sharpe ◽  
David Baskin ◽  
Santosh Helekar
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cell Viability ◽  
Cortical Neurons ◽  
Reactive Oxygen ◽  
Great Promise ◽  
Antioxidant Vitamin ◽  
Ros Generation ◽  
Oxygen Species ◽  
Novel Therapy

Abstract Noninvasive cancer therapy with minimal side effects would be ideal for improving patient outcome in the clinic. We have developed a novel therapy using strong rotating magnets mounted on a helmet. They generate oscillating magnetic fields (OMF) that penetrate through the skull and cover the entire brain. We have demonstrated that OMF can effectively kill patient derived glioblastoma (GBM) cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes (NHA). Exposure of GBM cells to OMF reduced the cell viability by 33% in comparison to sham-treated cells (p&lt; 0.001), while not affecting NHA cell viability. Time lapse video-microscopy for 16 h after OMF exposure showed a marked elevation of mitochondrial reactive oxygen species (ROS), and rapid apoptosis of GBM cells due to activation of caspase 3. Addition of a potent antioxidant vitamin E analog Trolox effectively blocked OMF-induced GBM cell death. Furthermore, OMF significantly potentiated the cytotoxic effect of the pro-oxidant Benzylamine. The results of our studies demonstrate that OMF-induced cell death is mediated by ROS generation. These results demonstrate a potent oncolytic effect on GBM cells that is novel and unrelated to any previously described therapy, including a very different mechanism of action and different technology compared to Optune therapy. The effect is very powerful, and unlike Optune, can be seen within hours after initiation of treatment. We believe that this technology holds great promise for new, effective and nontoxic treatment of glioblastoma.

Hepatocellular expression of glucose-6-phosphatase is unaltered during hepatic regeneration

1998 ◽  
Vol 275 (4) ◽  
pp. G717-G722 ◽  
Author(s):  
Wisam F. Zakko ◽  
Carl L. Berg ◽  
John L. Gollan ◽  
Richard M. Green
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Protein Expression ◽  
Partial Hepatectomy ◽  
Initial Phase ◽  
Physiological Function ◽  
Liver Homogenate ◽  
Hepatic Regeneration ◽  
Mrna Levels ◽  
Microsomal Enzyme

Gluconeogenesis and glycogenolysis are essential hepatic functions required for glucose homeostasis. During the initial phase of hepatic regeneration, the immediate-early genes (IEG) are rapidly expressed, and the IEG RL-1 encodes for glucose-6-phosphatase (G-6- Pase). G-6- Pase is a microsomal enzyme essential for gluconeogenesis and glycogenolysis. This study employs a partial-hepatectomy model to examine the expression and activity of G-6- Pase. After partial hepatectomy, rat hepatic G-6- Pase gene expression is transcriptionally regulated, and mRNA levels are increased ≈30-fold. However, in contrast to this rapid gene induction, microsomal enzyme activity is unchanged after partial hepatectomy. Western blotting demonstrates that microsomal G-6- Pase protein expression is also unchanged after partial hepatectomy, and similar results are also noted in whole liver homogenate. Thus, despite marked induction in gene expression of the IEG G-6- Pase after partial hepatectomy, protein expression and enzyme activity remain unchanged. These data indicate that, although this hepatocyte IEG is transcriptionally regulated, the physiologically important level of regulation is posttranscriptional. This highlights the importance of correlating gene expression of IEG with protein expression and physiological function.

scholarly journals A Novel Tetrapeptide Derivative Exhibits In Vitro Inhibition of Neutrophil-Derived Reactive Oxygen Species and Lysosomal Enzymes Release

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
Meera Ramanujam ◽  
Rengarajulu Puvanakrishnan
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Anion ◽  
Lysosomal Enzymes ◽  
Reactive Oxygen ◽  
Peptide Sequence ◽  
Ros Generation ◽  
Oxygen Species ◽  
Complement Factors

Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39–42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.

scholarly journals CYP450 Mediates Reactive Oxygen Species Production in a Mouse Model of β-Thalassemia through an Increase in 20-HETE Activity

2021 ◽  
Vol 22 (3) ◽  
pp. 1106
Author(s):  
Rayan Bou-Fakhredin ◽  
Batoul Dia ◽  
Hilda E. Ghadieh ◽  
Stefano Rivella ◽  
Maria Domenica Cappellini ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mouse Model ◽  
Cell Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Species Production ◽  
Different Sources ◽  
Dependent Pathway

Oxidative damage by reactive oxygen species (ROS) is one of the main contributors to cell injury and tissue damage in thalassemia patients. Recent studies suggest that ROS generation in non-transfusion-dependent (NTDT) patients occurs as a result of iron overload. Among the different sources of ROS, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes and cytochrome P450 (CYP450) have been proposed to be major contributors for oxidative stress in several diseases. However, the sources of ROS in patients with NTDT remain poorly understood. In this study, Hbbth3/+ mice, a mouse model for β-thalassemia, were used. These mice exhibit an unchanged or decreased expression of the major NOX isoforms, NOX1, NOX2 and NOX4, when compared to their C57BL/6 control littermates. However, a significant increase in the protein synthesis of CYP4A and CYP4F was observed in the Hbbth3/+ mice when compared to the C57BL/6 control mice. These changes were paralleled by an increased production of 20-hydroxyeicosatetraenoic acid (20-HETE), a CYP4A and CYP4F metabolite. Furthermore, these changes corroborate with onset of ROS production concomitant with liver injury. To our knowledge, this is the first report indicating that CYP450 4A and 4F-induced 20-HETE production mediates reactive oxygen species overgeneration in Hbbth3/+ mice through an NADPH-dependent pathway.

scholarly journals Ginger Oleoresin Alleviated γ-Ray Irradiation-Induced Reactive Oxygen Species via the Nrf2 Protective Response in Human Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Kaihua Ji ◽  
Lianying Fang ◽  
Hui Zhao ◽  
Qing Li ◽  
Yang Shi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Genes Encoding ◽  
Dna Strand

Unplanned exposure to radiation can cause side effects on high-risk individuals; meanwhile, radiotherapies can also cause injury on normal cells and tissues surrounding the tumor. Besides the direct radiation damage, most of the ionizing radiation- (IR-) induced injuries were caused by generation of reactive oxygen species (ROS). Human mesenchymal stem cells (hMSCs), which possess self-renew and multilineage differentiation capabilities, are a critical population of cells to participate in the regeneration of IR-damaged tissues. Therefore, it is imperative to search effective radioprotectors for hMSCs. This study was to demonstrate whether natural source ginger oleoresin would mitigate IR-induced injuries in human mesenchymal stem cells (hMSCs). We demonstrated that ginger oleoresin could significantly reduce IR-induced cytotoxicity, ROS generation, and DNA strand breaks. In addition, the ROS-scavenging mechanism of ginger oleoresin was also investigated. The results showed that ginger oleoresin could induce the translocation of Nrf2 to cell nucleus and activate the expression of cytoprotective genes encoding for HO-1 and NQO-1. It suggests that ginger oleoresin has a potential role of being an effective antioxidant and radioprotective agent.

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