Importance of post-transcriptional regulation of chemokine genes by oxidative stress

2001 ◽  
Vol 360 (2) ◽  
pp. 321-333 ◽  
Author(s):  
Claire JOSSE ◽  
Johan R. BOELAERT ◽  
Martin BEST-BELPOMME ◽  
Jacques PIETTE
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
De Novo ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
U937 Cells ◽  
Transient Transfection Assay ◽  
Mrna Species ◽  
Inflammatory Protein ◽  
Mitogen Activated Protein

The transcription factor, nuclear factor κB (NF-κB), is activated by various stimuli including cytokines, radiation, viruses and oxidative stress. Here we show that, although induction with H2O2 gives rise to NF-κB nuclear translocation in both lymphocyte (CEM) and monocyte (U937) cells, it leads only to the production of mRNA species encoding interleukin-8 (IL-8) and macrophage inflammatory protein 1α in U937 cells. Under similar conditions these mRNA species are not observed in CEM cells. With the use of a transient transfection assay of U937 cells transfected with reporter constructs of the IL-8 promoter and subsequently treated with H2O2, we show that (1) IL-8-promoter-driven transcription is stimulated in both U937 and CEM cells and (2) the NF-κB site is crucial for activation because its deletion abolishes activation by H2O2. The production of IL-8 mRNA in U937 cells is inhibited by the NF-κB inhibitors clasto-lactacystin-β-lactone and E-64D (l-3-trans-ethoxycarbonyloxirane-2-carbonyl-l-leucine-3-methyl amide) but requires protein synthesis de novo. Moreover, inhibition of the p38 mitogen-activated protein kinase also decreases the IL-8 mRNA up-regulation mediated by H2O2. Taken together, these results show the importance of post-transcriptional events controlled by a p38-dependent pathway in the production of IL-8 mRNA in U937. The much lower activation of p38 in CEM cells in response to H2O2 could explain the lack of stabilization of IL-8 mRNA in these cells.

scholarly journals Preventive Effect of YGDEY from Tilapia Fish Skin Gelatin Hydrolysates against Alcohol-Induced Damage in HepG2 Cells through ROS-Mediated Signaling Pathways

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 392 ◽  
Author(s):  
Mei-Fang Chen ◽  
Fang Gong ◽  
Yuanyuan Zhang ◽  
Cheng-Yong Li ◽  
Chun-Xia Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Fish Skin ◽  
Mitogen Activated Protein ◽  
Fish Skin Gelatin

According to a previous study, YGDEY from tilapia fish skin gelatin hydrolysates hasstrong free radical scavenging activity. In the present study, the protective effect of YGDEY againstoxidative stress induced by ethanol in HepG2 cells was investigated. First, cells were incubatedwith YGDEY (10, 20, 50, and 100 μM) to assess cytotoxicity, and there was no significant change incell viability. Next, it was established that YGDEY decreased the production of reactive oxygenspecies (ROS). Western blot results indicated that YGDEY increased the levels of superoxidedismutase (SOD) and glutathione (GSH) and decreased the expression ofgamma-glutamyltransferase (GGT) in HepG2 cells. It was then revealed that YGDEY markedlyreduced the expressions of bax and cleaved-caspase-3 (c-caspase-3); inhibited phosphorylation ofAkt, IκB-α, p65, and p38; and increased the level of bcl-2. Moreover, the comet assay showed thatYGDEY effectively decreased the amount of ethanol-induced DNA damage. Thus, YGDEYprotected HepG2 cells from alcohol-induced injury by inhibiting oxidative stress, and this may beassociated with the Akt/nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaltransduction pathways. These results demonstrate that YGDEY from tilapia fish skin gelatinhydrolysates protects HepG2 cells from oxidative stress, making it a potential functional foodingredient.

scholarly journals TAK1 Mediates ROS Generation Triggered by the Specific Cephalosporins through Noncanonical Mechanisms

2020 ◽  
Vol 21 (24) ◽  
pp. 9497
Author(s):  
Midori Suzuki ◽  
Yukino Asai ◽  
Tomohiro Kagi ◽  
Takuya Noguchi ◽  
Mayuka Yamada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Microscopic Analysis ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Mitogen Activated Protein

It is known that a wide variety of antibacterial agents stimulate generation of reactive oxygen species (ROS) in mammalian cells. However, its mechanisms are largely unknown. In this study, we unexpectedly found that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is involved in the generation of mitochondrial ROS (mtROS) initiated by cefotaxime (CTX), one of specific antibacterial cephalosporins that can trigger oxidative stress-induced cell death. TAK1-deficient macrophages were found to be sensitive to oxidative stress-induced cell death stimulated by H2O2. Curiously, however, TAK1-deficient macrophages exhibited strong resistance to oxidative stress-induced cell death stimulated by CTX. Microscopic analysis revealed that CTX-induced ROS generation was overridden by knockout or inhibition of TAK1, suggesting that the kinase activity of TAK1 is required for CTX-induced ROS generation. Interestingly, pharmacological blockade of the TAK1 downstream pathways, such as nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, did not affect the CTX-induced ROS generation. In addition, we observed that CTX promotes translocation of TAK1 to mitochondria. Together, these observations suggest that mitochondrial TAK1 mediates the CTX-induced mtROS generation through noncanonical mechanisms. Thus, our data demonstrate a novel and atypical function of TAK1 that mediates mtROS generation triggered by the specific cephalosporins.

scholarly journals Sphingosine Kinase 1 Regulates Tumor Necrosis Factor-mediated RANTES Induction through p38 Mitogen-activated Protein Kinase but Independently of Nuclear Factor κB Activation

2013 ◽  
Vol 288 (38) ◽  
pp. 27667-27679 ◽  
Author(s):  
Mohamad M. Adada ◽  
K. Alexa Orr-Gandy ◽  
Ashley J. Snider ◽  
Daniel Canals ◽  
Yusuf A. Hannun ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Nuclear Translocation ◽  
Sphingosine Kinase ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Sphingosine Kinase 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Sphingosine 1 Phosphate ◽  
Functional Consequences

Sphingosine kinase 1 (SK1) produces the pro-survival sphingolipid sphingosine 1-phosphate and has been implicated in inflammation, proliferation, and angiogenesis. Recent studies identified TRAF2 as a sphingosine 1-phosphate target, implicating SK1 in activation of the NF-κB pathway, but the functional consequences of this connection on gene expression are unknown. Here, we find that loss of SK1 potentiates induction of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted; also known as CCL5) in HeLa cells stimulated with TNF-α despite RANTES induction being highly dependent on the NF-κB pathway. Additionally, we find that SK1 is not required for TNF-induced IKK phosphorylation, IκB degradation, nuclear translocation of NF-κB subunits, and transcriptional NF-κB activity. In contrast, loss of SK1 prevented TNF-induced phosphorylation of p38 MAPK, and inhibition of p38 MAPK, like SK1 knockdown, also potentiates RANTES induction. Finally, in addition to RANTES, loss of SK1 also potentiated the induction of multiple chemokines and cytokines in the TNF response. Taken together, these data identify a potential and novel anti-inflammatory function of SK1 in which chemokine levels are suppressed through SK1-mediated activation of p38 MAPK. Furthermore, in this system, activation of NF-κB is dissociated from SK1, suggesting that the interaction between these pathways may be more complex than currently thought.

Age-Related Changes in Activation of Mitogen-Activated Protein Kinase Cascades by Oxidative Stress

1998 ◽  
Vol 3 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Kathryn Z Guyton ◽  
Myriani Gorospe ◽  
Xiantao Wang ◽  
Yolanda D Mock ◽  
Gertrude C Kokkonen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Age Related ◽  
Mitogen Activated Protein ◽  
Age Related Changes

Review of treatment and therapeutic targets in brain arteriovenous malformation

2021 ◽  
pp. 0271678X2110267
Author(s):  
Peipei Pan ◽  
Shantel Weinsheimer ◽  
Daniel Cooke ◽  
Ethan Winkler ◽  
Adib Abla ◽  
...  
Keyword(s):  
Animal Models ◽  
De Novo ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Current Treatment ◽  
Mitogen Activated Protein Kinase ◽  
De Novo Mutations ◽  
Genetic Syndromes ◽  
Mitogen Activated Protein

Brain arteriovenous malformations (bAVM) are an important cause of intracranial hemorrhage (ICH), especially in younger patients. The pathogenesis of bAVM are largely unknown. Current understanding of bAVM etiology is based on studying genetic syndromes, animal models, and surgically resected specimens from patients. The identification of activating somatic mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene and other mitogen-activated protein kinase ( MAPK) pathway genes has opened up new avenues for bAVM study, leading to a paradigm shift to search for somatic, de novo mutations in sporadic bAVMs instead of focusing on inherited genetic mutations. Through the development of new models and understanding of pathways involved in maintaining normal vascular structure and functions, promising therapeutic targets have been identified and safety and efficacy studies are underway in animal models and in patients. The goal of this paper is to provide a thorough review or current diagnostic and treatment tools, known genes and key pathways involved in bAVM pathogenesis to summarize current treatment options and potential therapeutic targets uncovered by recent discoveries.

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