Phenanthrene decreases neutrophil function by disrupting intracellular redox balance

2010 ◽  
pp. n/a-n/a
Author(s):  
M. H. P. Buttignol ◽  
M. P. Barros ◽  
R. C. Macedo ◽  
D. P. Marin ◽  
R. Otton
Keyword(s):  
Redox Balance ◽  
Neutrophil Function ◽  
Intracellular Redox

Glyap1 regulates pneumocandin B0 synthesis by controlling the intracellular redox balance in Glarea lozoyensis

2021 ◽  
Author(s):  
Yan Dong ◽  
Lei Zhang ◽  
Weiting Zhang ◽  
Jianan Cao ◽  
Yiping Wei ◽  
...  
Keyword(s):  
Redox Balance ◽  
Intracellular Redox

Disrupted intracellular redox balance of the diplomonad fish parasite Spironucleus vortens by 5-nitroimidazoles and garlic-derived compounds

2012 ◽  
Vol 190 (1-2) ◽  
pp. 62-73 ◽  
Author(s):  
C.F. Williams ◽  
D. Lloyd ◽  
D. Kolarich ◽  
K. Alagesan ◽  
M. Duchêne ◽  
...  
Keyword(s):  
Redox Balance ◽  
Fish Parasite ◽  
Intracellular Redox

Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Benjamin Steinhorn ◽  
Emrah Eroglu ◽  
Thomas Michel
Keyword(s):  
Dynamic Control ◽  
Cardiovascular Pharmacology ◽  
Redox Balance ◽  
Signaling Molecules ◽  
Annual Review ◽  
Publication Date ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Pharmacology And Toxicology ◽  
Intracellular Redox

Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance

2019 ◽  
Vol 116 (19) ◽  
pp. 9433-9442 ◽  
Author(s):  
Jonathan K. M. Lim ◽  
Alberto Delaidelli ◽  
Sean W. Minaker ◽  
Hai-Feng Zhang ◽  
Milena Colovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Redox Balance ◽  
Gene Encoding ◽  
Oncogenic Ras ◽  
Opposing Effects ◽  
Whole Transcriptome ◽  
Intracellular Redox

The RAS family of proto-oncogenes are among the most commonly mutated genes in human cancers and predict poor clinical outcome. Several mechanisms underlying oncogenic RAS transformation are well documented, including constitutive signaling through the RAF-MEK-ERK proproliferative pathway as well as the PI3K-AKT prosurvival pathway. Notably, control of redox balance has also been proposed to contribute to RAS transformation. However, how homeostasis between reactive oxygen species (ROS) and antioxidants, which have opposing effects in the cell, ultimately influence RAS-mediated transformation and tumor progression is still a matter of debate and the mechanisms involved have not been fully elucidated. Here, we show that oncogenic KRAS protects fibroblasts from oxidative stress by enhancing intracellular GSH levels. Using a whole transcriptome approach, we discovered that this is attributable to transcriptional up-regulation of xCT, the gene encoding the cystine/glutamate antiporter. This is in line with the function of xCT, which mediates the uptake of cystine, a precursor for GSH biosynthesis. Moreover, our results reveal that the ETS-1 transcription factor downstream of the RAS-RAF-MEK-ERK signaling cascade directly transactivates the xCT promoter in synergy with the ATF4 endoplasmic reticulum stress-associated transcription factor. Strikingly, xCT was found to be essential for oncogenic KRAS-mediated transformation in vitro and in vivo by mitigating oxidative stress, as knockdown of xCT strongly impaired growth of tumor xenografts established from KRAS-transformed cells. Overall, this study uncovers a mechanism by which oncogenic RAS preserves intracellular redox balance and identifies an unexpected role for xCT in supporting RAS-induced transformation and tumorigenicity.

Breaking the Intracellular Redox Balance with Diselenium Nanoparticles for Maximizing Chemotherapy Efficacy on Patient-Derived Xenograft Models

ACS Nano ◽  
2020 ◽  
Vol 14 (12) ◽  
pp. 16984-16996
Author(s):  
Dengshuai Wei ◽  
Yingjie Yu ◽  
Xingcai Zhang ◽  
Yongheng Wang ◽  
Hao Chen ◽  
...  
Keyword(s):  
Redox Balance ◽  
Patient Derived Xenograft ◽  
Xenograft Models ◽  
Chemotherapy Efficacy ◽  
Intracellular Redox

scholarly journals Regulation of prostate cancer cell invasion by modulation of extra- and intracellular redox balance

2012 ◽  
Vol 52 (2) ◽  
pp. 452-461 ◽  
Author(s):  
Luksana Chaiswing ◽  
Weixiong Zhong ◽  
Yongliang Liang ◽  
Dean P. Jones ◽  
Terry D. Oberley
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Prostate Cancer Cell ◽  
Redox Balance ◽  
Cancer Cell Invasion ◽  
Intracellular Redox

scholarly journals In vitro inhibition of topoisomerase IIα by reduced glutathione.

2011 ◽  
Vol 58 (2) ◽  
Author(s):  
Zahid M Delwar ◽  
Marina Fernanda Vita ◽  
Åke Siden ◽  
Mabel Cruz ◽  
Juan Sebastian Yakisich
Keyword(s):  
Redox Balance ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Topoisomerase Iiα ◽  
Physiological Concentration ◽  
Concentration Dependent Manner ◽  
Disulfide Exchange ◽  
Intracellular Redox

In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances. In this study, the inhibitory effect of physiological concentration of GSH and GSSG on topoisomerase IIα activity in vitro was investigated. GSH (0-10 mM) inhibited topoisomerase IIα in a concentration-dependent manner while GSSG (1-100 µM) had no significant effect. These findings suggest that the GSH/GSSG system could have a potential in vivo role in regulating topoisomerase IIα activity.

A biomimetic nanodrug self-assembled from small molecules for enhanced ferroptosis therapy

2022 ◽  
Author(s):  
Xueming Xu ◽  
Yuan Chen ◽  
Jinyong Gui ◽  
Peilian Liu ◽  
Yong Huang ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Cancer Treatment ◽  
Small Molecules ◽  
Antioxidant Defense ◽  
Redox Balance ◽  
Self Assembled ◽  
Intracellular Redox

The ferroptosis drugs often induce oxidative damage or block antioxidant defense due to the key mechanism of ferroptosis in cancer treatment involved regulating the intracellular redox balance. However, these ferroptosis...

scholarly journals Thiol-metabolizing proteins and endothelial redox state: differential modulation of eNOS and biopterin pathways

2010 ◽  
Vol 298 (1) ◽  
pp. H194-H201 ◽  
Author(s):  
Toru Sugiyama ◽  
Thomas Michel
Keyword(s):  
Endothelial Cells ◽  
Redox State ◽  
Nitrosative Stress ◽  
Redox Balance ◽  
Vascular Wall ◽  
Differential Regulation ◽  
No Production ◽  
Oxidative And Nitrosative Stress ◽  
Aortic Endothelial Cells ◽  
Intracellular Redox

The intracellular redox state is stringently maintained by thiol-based antioxidants to establish a balance for the physiological and pathophysiological roles of reactive oxygen species. The relative contributions of the thioredoxin (Trx) and glutathione/glutaredoxin systems to intracellular redox balance are incompletely understood, as are the consequences of altered thiol metabolism on endothelial nitric oxide (NO) synthase (eNOS) and NO-dependent pathways in the endothelium. We designed duplex small interfering RNA (siRNA) constructs to specifically “knock down” the expression of three key thiol-metabolizing enzymes in cultured aortic endothelial cells. Transfection of siRNA constructs targeting glutathione reductase (GR), cytosolic Trx reductase (TrxR1), or mitochondrial Trx reductase (TrxR2) significantly decreased the intracellular reduced glutathione-to-oxidized glutathione ratio. siRNA-mediated knockdown of either GR, TrxR1, or TrxR2 markedly suppressed VEGF-induced NO production (measured by an electrochemical NO sensor) and also blocked eNOS enzyme activity (using the [3H]arginine/[3H]citrulline assay). Pretreatment of endothelial cells with N, N′-bis(2-chloroethyl)- N-nitrosourea, an inhibitor of GR and TrxR, significantly decreased VEGF-induced NO production. siRNA-mediated TrxR2 knockdown led to a marked increase in hydrogen peroxide (H2O2) production in endothelial cells. In contrast, knockdown of GR or TrxR1 only slightly increased H2O2 production. Supplementation of endothelial cells with tetrahydrobiopterin prevented the increase in H2O2 generation seen with siRNA-mediated knockdown of GR. These studies show that the differential regulation of thiol-metabolizing proteins leads to critical changes in oxidative and nitrosative stress pathways. Greater understanding of the differential regulation of thiol-metabolizing proteins may lead to the development of new pharmacological targets for diseases associated with oxidative stress in the vascular wall.

966 Rapid Disturbance of the Intracellular Redox Balance Predicts Sensitivity to the Preclinical Anticancer Ruthenium Compound KP1339

2012 ◽  
Vol 48 ◽  
pp. S232
Author(s):  
K. Kryeziu ◽  
P. Heffeter ◽  
C. Pirker ◽  
Y. Senkiv ◽  
U. Jungwirth ◽  
...  
Keyword(s):  
Redox Balance ◽  
Ruthenium Compound ◽  
Intracellular Redox
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