scholarly journals Sorbitol accumulation decreases oocyte quality in aged mice by altering the intracellular redox balance

Aging ◽  
2021 ◽  
Author(s):  
Yuexin Zhang ◽  
Zhengjie Yan ◽  
Hanwen Liu ◽  
Lingjun Li ◽  
Chun Yuan ◽  
...  
Keyword(s):  
Redox Balance ◽  
Oocyte Quality ◽  
Aged Mice ◽  
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

scholarly journals Aged xCT-Deficient Mice Are Less Susceptible for Lactacystin-, but Not 1-Methyl-4-Phenyl-1,2,3,6- Tetrahydropyridine-, Induced Degeneration of the Nigrostriatal Pathway

2021 ◽  
Vol 15 ◽  
Author(s):  
Eduard Bentea ◽  
Laura De Pauw ◽  
Lise Verbruggen ◽  
Lila C. Winfrey ◽  
Lauren Deneyer ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Proteasome Inhibition ◽  
Cell Loss ◽  
Redox Balance ◽  
Nigrostriatal Pathway ◽  
Knock Out ◽  
Aged Mice ◽  
Adult Mice ◽  
Age Related ◽  
Nigrostriatal Degeneration

The astrocytic cystine/glutamate antiporter system xc– (with xCT as the specific subunit) imports cystine in exchange for glutamate and has been shown to interact with multiple pathways in the brain that are dysregulated in age-related neurological disorders, including glutamate homeostasis, redox balance, and neuroinflammation. In the current study, we investigated the effect of genetic xCT deletion on lactacystin (LAC)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of the nigrostriatal pathway, as models for Parkinson’s disease (PD). Dopaminergic neurons of adult xCT knock-out mice (xCT–/–) demonstrated an equal susceptibility to intranigral injection of the proteasome inhibitor LAC, as their wild-type (xCT+/+) littermates. Contrary to adult mice, aged xCT–/– mice showed a significant decrease in LAC-induced degeneration of nigral dopaminergic neurons, depletion of striatal dopamine (DA) and neuroinflammatory reaction, compared to age-matched xCT+/+ littermates. Given this age-related protection, we further investigated the sensitivity of aged xCT–/– mice to chronic and progressive MPTP treatment. However, in accordance with our previous observations in adult mice (Bentea et al., 2015a), xCT deletion did not confer protection against MPTP-induced nigrostriatal degeneration in aged mice. We observed an increased loss of nigral dopaminergic neurons, but equal striatal DA denervation, in MPTP-treated aged xCT–/– mice when compared to age-matched xCT+/+ littermates. To conclude, we reveal age-related protection against proteasome inhibition-induced nigrostriatal degeneration in xCT–/– mice, while xCT deletion failed to protect nigral dopaminergic neurons of aged mice against MPTP-induced toxicity. Our findings thereby provide new insights into the role of system xc– in mechanisms of dopaminergic cell loss and its interaction with aging.

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

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

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.

scholarly journals NMN treatment reverses unique deep radiomic signature morphology of oocytes from aged mice

2021 ◽  
Author(s):  
Abbas Habibalahi ◽  
Michael J. Bertoldo ◽  
Saabah B. Mahbub ◽  
Jared M. Campbell ◽  
Dale M. Goss ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Reproductive Potential ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Aged Mice ◽  
Nicotinamide Mononucleotide ◽  
Highly Sensitive ◽  
Reproductive Ageing ◽  
Bright Field Microscopy ◽  
The Impact

Abstract One of the earliest physiological consequences of advancing age is the loss of female reproductive potential. This is primarily due to oocyte quality and developmental competence, which is highly sensitive to biological age. We applied deep learning, swarm intelligence and discriminative analysis to images of mouse oocytes taken by common bright field microscopy and were successfully able to identify a highly informative deep radiomic signature (DRS) of oocyte age. This signature distinguished morphological changes in oocytes associated with maternal age with 92% accuracy (AUC~1), reflecting this decline in oocyte quality. We then employed the DRS to evaluate the impact of the treatment of reproductively aged mice with the NAD+ precursor nicotinamide mononucleotide (NMN). The DRS signature classified 60% of oocytes from NMN-treated aged mice as having a 'young' morphology, suggesting that NMN was able to rejuvenate the morphological changes identified by the DRS. These findings indicate that NMN therapy may be able to restore the quality of a sizable subset of oocytes affected by reproductive ageing, and that these oocytes will be able to be distinguished and selected by DRS.

Sign in / Sign up

Export Citation Format

Share Document