Faculty Opinions recommendation of Stimulus-induced downregulation of root water transport involves reactive oxygen species-activated cell signalling and plasma membrane intrinsic protein internalization.

Objectives: Experimental data indicate an important role for Toll-like Receptor 4 (TLR4) MyD88 independent signaling in upregulating Interferon β (IFN-β) production and driving atherosclerosis. We recently identified a distinct non-foam cell macrophage (M(Hb) or Hb-associated macrophage) in areas of intraplaque hemorrhage characterized by reduced reactive oxygen species (ROS) and pro-inflammatory cytokines. In this study, we investigated the role of iron and ROS in mediating TLR4 MyD88 independent signaling in these cells. Methods and Results: Areas rich in M(Hb) in atherosclerotic plaques demonstrated significantly reduced IFN-β expression compared to foam cell areas by immunostaining and quantitative PCR. M(Hb) did not upregulate IFN-β when exposed to ox LDL in contrast to control macrophages, a response which was inhibited in the presence of a TLR4 blocking antibody. To further investigate TLR4 responses in M(Hb), we used the TLR4 activator LPS. LPS produced significant increases in IFN-β in control macrophages but had no effect in M(Hb). This defect could be corrected by raising intracellular iron by pretreating M(Hb) with hepcidin prior to LPS treatment, suggesting redox state mediates this effect. The interaction of TLR4 with TRIF was examined by immunoprecipitation of lysates from control or M(Hb) cells treated with LPS using a TLR4 antibody and immunoblotting for TRIF. LPS treatment of control but not M(Hb) cells resulted in an increase in TRIF. Hepcidin pretreatment of M(Hb) corrected this interaction in response to LPS while differentiating monocytes in superoxide dismutase prevented it. Lastly, the interaction between lipid rafts and TLR4 was examined using FITC-cholera toxin (CTx) and a TLR4 antibody. In control cells the distribution of CTx on the plasma membrane was homogeneous and TLR4 localized to both the membrane and intracellular compartment. After LPS, a large fraction of TLR4 translocated to the plasma membrane, and colocalization of TLR4 and CTx was observed. In M(Hb) the LPS- induced translocation of TLR4 to the membrane rafts was inhibited. Conclusion: M(Hb) cells modulate TLR4 MyD88 independent signaling through reducing ROS which inhibits TLR4 lipid raft interactions.

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Effects of reactive oxygen species on brain synaptic plasma membrane Ca2+-ATPase

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(99)00128-8 ◽

1999 ◽

Vol 27 (7-8) ◽

pp. 810-821 ◽

Cited By ~ 104

Author(s):

Asma Zaidi ◽

Mary L. Michaelis

Keyword(s):

Reactive Oxygen Species ◽

Plasma Membrane ◽

Reactive Oxygen ◽

Synaptic Plasma Membrane ◽

Oxygen Species

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Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium

Biochemical Society Transactions ◽

10.1042/bst0331385 ◽

2005 ◽

Vol 33 (6) ◽

pp. 1385-1389 ◽

Cited By ~ 43

Author(s):

J.W. Zmijewski ◽

A. Landar ◽

N. Watanabe ◽

D.A. Dickinson ◽

N. Noguchi ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Lipid Oxidation ◽

Protein Function ◽

Cell Signalling ◽

Reactive Oxygen ◽

Oxidation Products ◽

Oxidized Lipids ◽

Oxygen Species ◽

Post Translational Modification ◽

Lipid Oxidation Products

The controlled formation of ROS (reactive oxygen species) and RNS (reactive nitrogen species) is now known to be critical in cellular redox signalling. As with the more familiar phosphorylation-dependent signal transduction pathways, control of protein function is mediated by the post-translational modification at specific amino acid residues, notably thiols. Two important classes of oxidant-derived signalling molecules are the lipid oxidation products, including those with electrophilic reactive centres, and decomposition products such as lysoPC (lysophosphatidylcholine). The mechanisms can be direct in the case of electrophiles, as they can modify signalling proteins by post-translational modification of thiols. In the case of lysoPC, it appears that secondary generation of ROS/RNS, dependent on intracellular calcium fluxes, can cause the secondary induction of H2O2 in the cell. In either case, the intracellular source of ROS/RNS has not been defined. In this respect, the mitochondrion is particularly interesting since it is now becoming apparent that the formation of superoxide from the respiratory chain can play an important role in cell signalling, and oxidized lipids can stimulate ROS formation from an undefined source. In this short overview, we describe recent experiments that suggest that the cell signalling mediated by lipid oxidation products involves their interaction with mitochondria. The implications of these results for our understanding of adaptation and the response to stress in cardiovascular disease are discussed.

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NADPH Oxidase-Mediated Reactive Oxygen Species Production: Subcellular Localization and Reassessment of Its Role in Plant Defense

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-22-7-0868 ◽

2009 ◽

Vol 22 (7) ◽

pp. 868-881 ◽

Cited By ~ 55

Author(s):

Jeannine Lherminier ◽

Taline Elmayan ◽

Jérôme Fromentin ◽

Khadija Tantaoui Elaraqui ◽

Simona Vesa ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Hydrogen Peroxide ◽

Plasma Membrane ◽

Nadph Oxidase ◽

Subcellular Localization ◽

Acquired Resistance ◽

Reactive Oxygen ◽

Oxygen Species ◽

Wild Type ◽

Hydrogen Peroxide Production

Chemiluminescence detection of reactive oxygen species (ROS) triggered in tobacco BY-2 cells by the fungal elicitor cryptogein was previously demonstrated to be abolished in cells transformed with an antisense construct of the plasma membrane NADPH oxidase, NtrbohD. Here, using electron microscopy, it has been confirmed that the first hydrogen peroxide production occurring a few minutes after challenge of tobacco cells with cryptogein is plasma membrane located and NtrbohD mediated. Furthermore, the presence of NtrbohD in detergent-resistant membrane fractions could be associated with the presence of NtrbohD-mediated hydrogen peroxide patches along the plasma membrane. Comparison of the subcellular localization of ROS in wild-type tobacco and in plants transformed with antisense constructs of NtrbohD revealed that this enzyme is also responsible for the hydrogen peroxide production occurring at the plasma membrane after infiltration of tobacco leaves with cryptogein. Finally, the reactivity of wild-type and transformed plants to the elicitor and their resistance against the pathogenic oomycete Phytophthora parasitica were examined. NtrbohD-mediated hydrogen peroxide production does not seem determinant for either hypersensitive response development or the establishment of acquired resistance but it is most likely involved in the signaling pathways associated with the protection of the plant cell.

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Oxidative stress in marathon runners: interest of antioxidant supplementation

British Journal Of Nutrition ◽

10.1079/bjn20061696 ◽

2006 ◽

Vol 96 (S1) ◽

pp. S31-S33 ◽

Cited By ~ 67

Author(s):

Mari-Carmen Gomez-Cabrera ◽

Agustín Martínez ◽

Gustavo Santangelo ◽

Federico V. Pallardó ◽

Juan Sastre ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Xanthine Oxidase ◽

Cell Signalling ◽

Reactive Oxygen ◽

Peripheral Blood Lymphocytes ◽

Signalling Pathways ◽

Marathon Running ◽

Oxygen Species ◽

Marathon Runners

We have recently reported that xanthine oxidase is involved in the generation of free radicals in exhaustive exercise. Allopurinol, an inhibitor of xanthine oxidase, prevents it. The aim of the present work was to elucidate the role of exercise-derived reactive oxygen species in the cell signalling pathways involved in the adaptation to exercise in man. We have found that exercise causes an increase in the activity of plasma xanthine oxidase and an activation of NF-κB in peripheral blood lymphocytes after marathon running. This activation is dependent on free radical formation in exercise: treatment with allopurinol completely prevents it. In animal models, we previously showed that NF-κB activation induced by exhaustive physical exercise leads to an increase in the expression of superoxide dismutase, an enzyme involved in antioxidant defence. We report evidence in man that reactive oxygen species act as signals in exercise as decreasing their formation prevents activation of important signalling pathways which can cause useful adaptations in cells.

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