Redox-regulation of Erk1/2-directed phosphatase by reactive oxygen species: Role in signaling TPA-induced growth arrest in ML-1 cells

AbstractUltraviolet A (UVA) radiation is harmful for living organisms but in low doses may stimulate cell proliferation. Our aim was to examine the relationships between exposure to different low UVA doses, cellular proliferation, and changes in cellular reactive oxygen species levels. In human colon cancer (HCT116) and melanoma (Me45) cells exposed to UVA doses comparable to environmental, the highest doses (30-50 kJ/m2) reduced clonogenic potential but some lower doses (1 and 10 kJ/m2) induced proliferation. This effect was cell type and dose specific. In both cell lines the levels of reactive oxygen species and nitric oxide fluctuated with dynamics which were influenced differently by UVA; in Me45 cells decreased proliferation accompanied the changes in the dynamics of H2O2 while in HCT116 cells those of superoxide. Genes coding for proteins engaged in redox systems were expressed differently in each cell line; transcripts for thioredoxin, peroxiredoxin and glutathione peroxidase showed higher expression in HCT116 cells whereas those for glutathione transferases and copper chaperone were more abundant in Me45 cells. We conclude that these two cell types utilize different pathways for regulating their redox status. Many mechanisms engaged in maintaining cellular redox balance have been described. Here we show that the different cellular responses to a stimulus such as a specific dose of UVA may be consequences of the use of different redox control pathways. Assays of superoxide and hydrogen peroxide level changes after exposure to UVA may clarify mechanisms of cellular redox regulation and help in understanding responses to stressing factors.

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Reactive oxygen species oxidize STING and suppress interferon production

eLife ◽

10.7554/elife.57837 ◽

2020 ◽

Vol 9 ◽

Author(s):

Lili Tao ◽

Andrew Lemoff ◽

Guoxun Wang ◽

Christina Zarek ◽

Alexandria Lowe ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Redox Regulation ◽

Reactive Oxygen ◽

Interferon Response ◽

Cellular Respiration ◽

Type I ◽

Oxygen Species ◽

Interferon Production ◽

Dna Sensing ◽

Cytoplasmic Dna

Reactive oxygen species (ROS) are by-products of cellular respiration that can promote oxidative stress and damage cellular proteins and lipids. One canonical role of ROS is to defend the cell against invading bacterial and viral pathogens. Curiously, some viruses, including herpesviruses, thrive despite the induction of ROS, suggesting that ROS are beneficial for the virus. However, the underlying mechanisms remain unclear. Here, we found that ROS impaired interferon response during murine herpesvirus infection and that the inhibition occurred downstream of cytoplasmic DNA sensing. We further demonstrated that ROS suppressed the type I interferon response by oxidizing Cysteine 147 on murine stimulator of interferon genes (STING), an ER-associated protein that mediates interferon response after cytoplasmic DNA sensing. This inhibited STING polymerization and activation of downstream signaling events. These data indicate that redox regulation of Cysteine 147 of mouse STING, which is equivalent to Cysteine 148 of human STING, controls interferon production. Together, our findings reveal that ROS orchestrates anti-viral immune responses, which can be exploited by viruses to evade cellular defenses.

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Redox Regulation and Oxidative Stress: The Particular Case of the Stallion Spermatozoa

Antioxidants ◽

10.3390/antiox8110567 ◽

2019 ◽

Vol 8 (11) ◽

pp. 567 ◽

Cited By ~ 11

Author(s):

Fernando J. Peña ◽

Cristian O’Flaherty ◽

José M. Ortiz Rodríguez ◽

Francisco E. Martín Cano ◽

Gemma L. Gaitskell-Phillips ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Redox Regulation ◽

Redox Homeostasis ◽

Reactive Oxygen ◽

Mitochondrial Activity ◽

Oxygen Species ◽

Redox Biology ◽

Major Interest ◽

And Oxidative Stress

Redox regulation and oxidative stress have become areas of major interest in spermatology. Alteration of redox homeostasis is recognized as a significant cause of male factor infertility and is behind the damage that spermatozoa experience after freezing and thawing or conservation in a liquid state. While for a long time, oxidative stress was just considered an overproduction of reactive oxygen species, nowadays it is considered as a consequence of redox deregulation. Many essential aspects of spermatozoa functionality are redox regulated, with reversible oxidation of thiols in cysteine residues of key proteins acting as an “on–off” switch controlling sperm function. However, if deregulation occurs, these residues may experience irreversible oxidation and oxidative stress, leading to malfunction and ultimately death of the spermatozoa. Stallion spermatozoa are “professional producers” of reactive oxygen species due to their intense mitochondrial activity, and thus sophisticated systems to control redox homeostasis are also characteristic of the spermatozoa in the horse. As a result, and combined with the fact that embryos can easily be collected in this species, horses are a good model for the study of redox biology in the spermatozoa and its impact on the embryo.

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Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells

Molecular Carcinogenesis ◽

10.1002/mc.22014 ◽

2013 ◽

Vol 53 (7) ◽

pp. 537-547 ◽

Cited By ~ 48

Author(s):

Trinath P. Das ◽

Suman Suman ◽

Chendil Damodaran

Keyword(s):

Prostate Cancer ◽

Reactive Oxygen Species ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Growth Arrest ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Prostate Cancer Cells ◽

Mesenchymal Transition

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Bcl-xLand E1B-19K Proteins Inhibit p53-induced Irreversible Growth Arrest and Senescence by Preventing Reactive Oxygen Species-dependent p38 Activation

Journal of Biological Chemistry ◽

10.1074/jbc.m305015200 ◽

2004 ◽

Vol 279 (17) ◽

pp. 17765-17771 ◽

Cited By ~ 44

Author(s):

Mun-Su Jung ◽

Dong-Hoon Jin ◽

Hee-Don Chae ◽

Seokwon Kang ◽

Sun-Chang Kim ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Growth Arrest ◽

Reactive Oxygen ◽

Oxygen Species

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Reactive oxygen species and redox regulation in mesophyll and bundle sheath cells of C4 plants

Journal of Experimental Botany ◽

10.1093/jxb/ery064 ◽

2018 ◽

Vol 69 (14) ◽

pp. 3321-3331 ◽

Cited By ~ 11

Author(s):

Ismail Turkan ◽

Baris Uzilday ◽

Karl-Josef Dietz ◽

Andrea Bräutigam ◽

Rengin Ozgur

Keyword(s):

Reactive Oxygen Species ◽

Redox Regulation ◽

Reactive Oxygen ◽

Bundle Sheath ◽

C4 Plants ◽

Oxygen Species ◽

Bundle Sheath Cells ◽

Sheath Cells

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Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus

Journal of Biological Chemistry ◽

10.1074/jbc.m115.674861 ◽

2015 ◽

Vol 291 (4) ◽

pp. 1974-1990 ◽

Cited By ~ 23

Author(s):

Donna N. Douglas ◽

Christopher Hao Pu ◽

Jamie T. Lewis ◽

Rakesh Bhat ◽

Anwar Anwar-Mohamed ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Growth Arrest ◽

Lipid Synthesis ◽

Reactive Oxygen ◽

Hcv Infection ◽

Peroxisome Proliferator ◽

Oxygen Species ◽

Peroxisome Proliferator Activated Receptor

Cytopathic effects are currently believed to contribute to hepatitis C virus (HCV)-induced liver injury and are readily observed in Huh7.5 cells infected with the JFH-1 HCV strain, manifesting as apoptosis highly correlated with growth arrest. Reactive oxygen species, which are induced by HCV infection, have recently emerged as activators of AMP-activated protein kinase. The net effect is ATP conservation via on/off switching of metabolic pathways that produce/consume ATP. Depending on the scenario, this can have either pro-survival or pro-apoptotic effects. We demonstrate reactive oxygen species-mediated activation of AMP-activated kinase in Huh7.5 cells during HCV (JFH-1)-induced growth arrest. Metabolic labeling experiments provided direct evidence that lipid synthesis is attenuated, and β-oxidation is enhanced in these cells. A striking increase in nuclear peroxisome proliferator-activated receptor α, which plays a dominant role in the expression of β-oxidation genes after ligand-induced activation, was also observed, and we provide evidence that peroxisome proliferator-activated receptor α is constitutively activated in these cells. The combination of attenuated lipid synthesis and enhanced β-oxidation is not conducive to lipid accumulation, yet cellular lipids still accumulated during this stage of infection. Notably, the serum in the culture media was the only available source for polyunsaturated fatty acids, which were elevated (2-fold) in the infected cells, implicating altered lipid import/export pathways in these cells. This study also provided the first in vivo evidence for enhanced β-oxidation during HCV infection because HCV-infected SCID/Alb-uPA mice accumulated higher plasma ketones while fasting than did control mice. Overall, this study highlights the reprogramming of hepatocellular lipid metabolism and bioenergetics during HCV infection, which are predicted to impact both the HCV life cycle and pathogenesis.

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Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling

Cellular Signalling ◽

10.1016/j.cellsig.2012.01.008 ◽

2012 ◽

Vol 24 (5) ◽

pp. 981-990 ◽

Cited By ~ 1964

Author(s):

Paul D. Ray ◽

Bo-Wen Huang ◽

Yoshiaki Tsuji

Keyword(s):

Reactive Oxygen Species ◽

Redox Regulation ◽

Cellular Signaling ◽

Reactive Oxygen ◽

Oxygen Species ◽

Ros Homeostasis

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Reactive Oxygen Species in Health and Disease

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/936486 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 280

Author(s):

Assim A. Alfadda ◽

Reem M. Sallam

Keyword(s):

Reactive Oxygen Species ◽

Redox Regulation ◽

Wide Spectrum ◽

Biological Effects ◽

Reactive Oxygen ◽

Oxygen Species ◽

Metabolic Products ◽

Health And Disease ◽

Regulatory Functions ◽

Cellular Organelles

During the past decades, it became obvious that reactive oxygen species (ROS) exert a multitude of biological effects covering a wide spectrum that ranges from physiological regulatory functions to damaging alterations participating in the pathogenesis of increasing number of diseases. This review summarizes the key roles played by the ROS in both health and disease. ROS are metabolic products arising from various cells; two cellular organelles are intimately involved in their production and metabolism, namely, the endoplasmic reticulum and the mitochondria. Updates on research that tremendously aided in confirming the fundamental roles of both organelles in redox regulation will be discussed as well. Although not comprehensive, this review will provide brief perspective on some of the current research conducted in this area for better understanding of the ROS actions in various conditions of health and disease.

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