Abstract 3028: Reactive oxygen species induced nuclear translocation of c-MET via INTERNET mechanism

2017 ◽  
Author(s):  
Mei-Kuang Chen ◽  
Yi Du ◽  
Yu-Yi Chu ◽  
Mien-Chie Hung
Keyword(s):  
Reactive Oxygen Species ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Oxygen Species

Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP

2006 ◽  
Vol 290 (5) ◽  
pp. F1169-F1176 ◽  
Author(s):  
Xiaoming Zhou ◽  
Joan D. Ferraris ◽  
Maurice B. Burg
Keyword(s):  
Reactive Oxygen Species ◽  
Transcription Factor ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Hek293 Cells ◽  
Organic Osmolytes ◽  
Ros Production ◽  
Oxygen Species ◽  
Hypertonic Stress ◽  
Mitochondrial Ros

Hypertonicity activates the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP), resulting in increased expression of genes involved in osmoprotective accumulation of organic osmolytes, including glycine betaine, and in increased expression of osmoprotective heat shock proteins. Our previous studies showed that high NaCl increases reactive oxygen species (ROS), which contribute to activation of TonEBP/OREBP. Mitochondria are a major source of ROS. The purpose of the present study was to examine whether mitochondria produce the ROS that contribute to activation of TonEBP/OREBP. We inhibited mitochondrial ROS production in HEK293 cells with rotenone and myxothiazol, which inhibit mitochondrial complexes I and III, respectively. Rotenone (250 nM) and myxothiazol (12 nM) reduce high NaCl-induced ROS over 40%, whereas apocynin (100 μM), an inhibitor of NADPH oxidase, and allopurinol (100 μM), an inhibitor of xanthine oxidase, have no significant effect. Rotenone and myxothiazol reduce high NaCl-induced increases in TonEBP/OREBP transcriptional activity (ORE/TonE reporter assay) and BGT1 (betaine transporter) mRNA abundance ranging from 53 to 69%. They inhibit high NaCl-induced TonEBP/OREBP transactivating activity, but not its nuclear translocation. Release of ATP into the medium on hypertonic stress has been proposed to be a signal that triggers cellular osmotic responses. However, we do not detect release of ATP into the medium or inhibition of high NaCl-induced ORE/TonE reporter activity by an ATPase, apyrase (20 U/ml), indicating that high NaCl-induced activation of TonEBP/OREBP is not mediated by release of ATP. We conclude that high NaCl increases mitochondrial ROS production, which contributes to the activation of TonEBP/OREBP by increasing its transactivating activity.

Regulation of IGF binding protein-1 in Hep G2 cells by cytokines and reactive oxygen species

1999 ◽  
Vol 276 (3) ◽  
pp. G719-G727 ◽  
Author(s):  
Charles H. Lang ◽  
Gerald J. Nystrom ◽  
Robert A. Frost
Keyword(s):  
Reactive Oxygen Species ◽  
Nuclear Translocation ◽  
Binding Protein ◽  
Reactive Oxygen ◽  
Free Radical Scavengers ◽  
Oxygen Species ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Tnf Α ◽  
G2 Cells

The liver is a major site of synthesis for insulin-like growth factor binding protein (IGFBP)-1. Because IGFBP-1 inhibits many anabolic actions of IGF-I, increases in IGFBP-1 may be partly responsible for the decrease in lean body mass observed in catabolic/inflammatory conditions. This study aimed to determine in Hep G2 cells 1) the sensitivity of IGFBP-1 synthesis to treatment with interleukin (IL)-1, tumor necrosis factor-α (TNF-α), and IL-6, 2) the ability of reactive oxygen species (ROS) to enhance IGFBP-1 production, and 3) the role of ROS in mediating cytokine-induced increases in IGFBP-1. Hep G2 cells responded to IL-1β, TNF-α, and IL-6 with maximal 8- to 10-fold increases in IGFBP-1 production. Although the maximal responsiveness of cells treated with TNF-α and IL-6 was 20–30% less than that with IL-1β, cells demonstrated a similar sensitivity to all cytokines (half-maximal responsive dose of ∼10 ng/ml). A low concentration (3 ng/ml) of all three cytokines had an additive effect on IGFBP-1 production. Cytokines also increased IGFBP-1 mRNA. The half-life of IGFBP-1 mRNA was ∼4 h and not altered by IL-1β. Incubation with ROS, including H2O2and nitric oxide (NO) donors, resulted in a relatively smaller increase in IGFBP-1. However, preincubating Hep G2 cells with various free radical scavengers and NO synthase and eicosanoid inhibitors failed to prevent or attenuate cytokine-induced increases in IGFBP-1. Finally, preincubating cells with pyrrolidinedithiocarbamate (PDTC) but not SN50 (inhibitors of nuclear factor-κB activation and nuclear translocation, respectively) attenuated increases in IGFBP-1 induced by IL-1. These results indicate that 1) proinflammatory cytokines directly enhance IGFBP-1 synthesis by stimulating transcription without altering mRNA stability, 2) addition of exogenous ROS also stimulates IGFBP-1 production but to a smaller extent than cytokines, and 3) the cytokine-induced increase in IGFBP-1 production is not mediated by endogenous production of ROS or eicosanoids but appears to at least partially involve a PDTC-sensitive pathway.

scholarly journals Respiratory Syncytial Virus Infection Induces a Reactive Oxygen Species-MSK1-Phospho-Ser-276 RelA Pathway Required for Cytokine Expression

2009 ◽  
Vol 83 (20) ◽  
pp. 10605-10615 ◽  
Author(s):  
Mohammad Jamaluddin ◽  
Bing Tian ◽  
Istvan Boldogh ◽  
Roberto P. Garofalo ◽  
Allan R. Brasier
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Respiratory Syncytial Virus ◽  
Inflammatory Response ◽  
Target Gene ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Target Gene Expression ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a human pathogen that induces airway inflammation, at least in part, by modulating gene expression programs in airway epithelial cells. The presence of RSV replication is detected by the intracellular retinoic acid-inducible gene I (RIG-I) RNA helicase that forms a productive signaling complex with the mitochondrion-anchored MAVS protein, resulting in nuclear translocation of the NF-κB transcription factor. Although nuclear translocation is a prerequisite for activation of the innate inflammatory response, recent studies show that separate pathways governing RelA activation are also required for target gene expression. In this study, we examine the mechanism of RelA phosphorylation and its requirement for RSV-induced gene expression. RSV infection produced a time-dependent RelA phosphorylation on serine (Ser) residues Ser-276 and Ser-536 in parallel with enhanced reactive oxygen species (ROS) stress. Inhibition of RSV-induced ROS inhibited formation of phospho-Ser-276 RelA without affecting phospho-Ser-536 RelA formation. RSV potently induced activation of cytoplasmic mitogen- and stress-related kinase 1 (MSK1) in an ROS-dependent manner. Inhibition of MSK1 using H89 and small interfering RNA knockdown both reduced RSV-induced phospho-Ser-276 RelA formation and expression of a subset of NF-κB-dependent genes. Direct examination of the role of phospho-Ser-276 in target gene expression by expression of a RelA Ser-276-to-Ala site mutation in RelA−/− mouse embryonic fibroblasts showed that the mutation was unable to mediate RSV-induced NF-κB-dependent gene expression. We conclude that RSV induces RelA activation in the innate inflammatory response via a pathway separate from that controlling RelA cytoplasmic release, mediated by ROS signaling to cytoplasmic MSK1 activation and RelA Ser-276 phosphorylation.

The protects of deep sea water against photoaging of HaCaT keratinocyte induced by UVB via suppression MMPs and MAPKs/NF-κB signaling pathway

2021 ◽  
Author(s):  
Xiaolei Ma ◽  
Duomo Duan ◽  
Baolong Xie ◽  
Xunliang Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Inflammatory Response ◽  
Nuclear Translocation ◽  
Sea Water ◽  
Reactive Oxygen ◽  
Collagen Degradation ◽  
Ultraviolet B ◽  
Oxygen Species ◽  
Uvb Irradiation ◽  
The Impact

Abstract Ultraviolet radiation destroys skin through several harmful effects, like inducing reactive oxygen species, inflammatory response, and collagen degradation. In this study we researched the impact of deep seawater (DSW) on the photoaging of HaCaT keratinocytes induced by ultraviolet B (UVB). DSW can inhibit epidermal hyperplasia and collagen degradation, increase skin moisture and hydroxyproline content, thereby improving the macro and histopathological damage of skin under UVB irradiation. Besides, DSW can inhibit UVB-induced oxidative stress (OS), improve antioxidant enzyme activity and inhibit the cellular signal transduction pathway of inflammatory response. Results showed DSW curbed the UVB irradiated levels of reactive oxygen species, superoxide dismutase (SOD), oxidative enzyme, glutathione peroxidase (GSH-Px), proinflammatory cytokines (TNF-α, IL-6). DSW prevented UVB-induced photoaging by suppressing collagen disorientation and expression of MMPs induced by UVB. Moreover, Western blot analyses exhibited that DSW significantly lessened the protein levels of phosphorylated SAPK/JNK kinase, phosphorylated ERK1/2 kinase, and phosphorylated p38 kinase. Similarly, UVB induced nuclear translocation of nuclear factor kappa-B were diminished by treatment of DSW. Therefore, DSW may lessen skin OS and inflammatory response under UVB irradiation. These data suggest that DSW can be used as a potentially effective skin care and dietary supplement for attenuating UVB-induced premature skin aging.

scholarly journals Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid

2015 ◽  
Vol 291 (4) ◽  
pp. 1933-1947 ◽  
Author(s):  
Andrea Comba ◽  
Luciana L. Almada ◽  
Ezequiel J. Tolosa ◽  
Eriko Iguchi ◽  
David L. Marks ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Transcription Factor ◽  
Arachidonic Acid ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Down Regulation ◽  
Induced Apoptosis

Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells. We demonstrated that down-regulation of the transcription factor glioma-associated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AA-induced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.

Ischemic Preconditioning Reduces Apoptosis By Upregulating Anti-Death Gene Bcl-2

Circulation ◽  
1999 ◽  
Vol 100 (suppl_2) ◽  
Author(s):  
Nilanjana Maulik ◽  
Richard M. Engelman ◽  
John A. Rousou ◽  
Joseph E. Flack ◽  
David Deaton ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Ischemic Preconditioning ◽  
Crucial Role ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Cardiomyocyte Apoptosis ◽  
Oxygen Species ◽  
Antioxidant Gene ◽  
Signaling Process

Background —Reperfusion of ischemic myocardium causes cardiomyocyte apoptosis in concert with downregulation of Bcl-2 gene. Ischemic preconditioning (PC) mediated by cyclic episodes of short-term ischemia and reperfusion reduces apoptotic cell death. PC also triggers a signaling pathway by potentiating tyrosine kinase phosphorylation leading to the activation of p38 MAP kinase and MAPKAP kinase 2. The nuclear transcription factor, NFκB, plays a crucial role in this signaling process. Because NFκB is a target of oxygen free radicals and Bcl-2 is an antioxidant gene, we hypothesized that reactive oxygen species might play a role in the signaling process. Methods and Results —Isolated rat hearts were perfused in the absence or presence of either dimethyl thiourea (DMTU), a hydroxyl radical scavenger, or SN50 peptide, a NFκB blocker. Hearts were then subjected to PC by 4 repeated episodes of 5-minute ischemia, each followed by 10 minutes reperfusion. All hearts were then made globally ischemic at normothermia for 30 minutes followed by 2 hours of normothermic reperfusion. Creatine kinase release and malonaldehyde formation were determined in the coronary effluent collected during reperfusion. At the end of each experiment, hearts were processed for infarct size determination and analyses of apoptosis, DNA fragmentation, NFκB, and Bcl-2. Myocardial infarction was reduced by PC. DMTU and SN50 abolished this cardioprotective effect of PC. PC resulted upregulation of Bcl-2 gene which was partially prevented by DMTU and SN50. Both ischemia/reperfusion and PC caused nuclear translocation and activation of NFκB, which was blocked by both DMTU and SN50. PC reduced cardiomyocyte apoptosis which was partially inhibited by DMTU and SN50. A substantial number of apoptotic cardiomyocytes were identified in the hearts subjected to 30 minutes ischemia and 2-hour reperfusion. PC significantly inhibited the extent of cardiomyocyte apoptosis and DMTU and SN50 reversed it only minimally. Conclusions —The results demonstrate that reactive oxygen species play a crucial role in signal transduction mediated by PC. This signaling process appears to involve NFκB. NFκB becomes translocated and activated by both ischemia/reperfusion, which induces apoptosis and PC which reduces apoptosis. However, the amount of NFκB binding activity is significantly higher in the PC hearts compared with ischemic reperfused hearts. The upregulation of the antioxidant gene, Bcl-2, is inversely correlated with the reduction of cardiomyocyte apoptosis associated with PC.

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