scholarly journals Do Connexin Mutants Cause Cataracts by Perturbing Glutathione Levels and Redox Metabolism in the Lens?

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1418
Author(s):  
Oscar Jara ◽  
Peter J. Minogue ◽  
Viviana M. Berthoud ◽  
Eric C. Beyer
Keyword(s):  
Oxidative Damage ◽  
Reduced Glutathione ◽  
Oxidative Modification ◽  
Glutathione Metabolism ◽  
Early Event ◽  
Oxidized Glutathione ◽  
Cataract Formation ◽  
Redox Metabolism ◽  
Gap Junction Channels ◽  
Mouse Lines

Cataracts of many different etiologies are associated with oxidation of lens components. The lens is protected by maintenance of a pool of reduced glutathione (GSH) and other antioxidants. Because gap junction channels made of the lens connexins, Cx46 and Cx50, are permeable to GSH, we tested whether mice expressing two different mutants, Cx46fs380 and Cx50D47A, cause cataracts by impairing lens glutathione metabolism and facilitating oxidative damage. Levels of GSH were not reduced in homogenates of whole mutant lenses. Oxidized glutathione (GSSG) and the GSSG/GSH ratio were increased in whole lenses of Cx50D47A, but not Cx46fs380 mice. The GSSG/GSH ratio was increased in the lens nucleus (but not cortex) of Cx46fs380 mice at 4.5 months of age, but it was not altered in younger animals. Carbonylated proteins were increased in Cx50D47A, but not Cx46fs380 lenses. Thus, both mouse lines have oxidizing lens environments, but oxidative modification is greater in Cx50D47A than in Cx46fs380 mice. The results suggest that GSH permeation through lens connexin channels is not a critical early event in cataract formation in these mice. Moreover, because oxidative damage was only detected in animals with significant cataracts, it cannot be an early event in their cataractogenesis.

Glutathione metabolism in heart and liver of the aging rat

1994 ◽  
Vol 72 (1-2) ◽  
pp. 58-61 ◽  
Author(s):  
M. Stio ◽  
T. Iantomasi ◽  
F. Favilli ◽  
P. Marraccini ◽  
B. Lunghi ◽  
...  
Keyword(s):  
Rat Heart ◽  
Reduced Glutathione ◽  
Age Groups ◽  
Glutathione Metabolism ◽  
Oxidized Glutathione ◽  
Glutathione S Transferase ◽  
Age Related ◽  
Glutamylcysteine Synthetase ◽  
Old Rats ◽  
Glucose 6 Phosphate Dehydrogenase

A comprehensive study on glutathione metabolism in rat heart and liver as a function of age was performed. In the heart, reduced glutathione, total glutathione, and the glutathione redox index showed a decrease during aging, while oxidized glutathione levels increased in 5-month-old rats with respect to the young animals and remained quite constant in 14- and 27-month-old rats. In the liver, the highest levels of reduced glutathione were found in the 2-month-old rats, while oxidized glutathione reached a peak at 5 months. Glutathione-associated enzymes showed age-related changes. Glutathione peroxidase, unaffected by aging in the heart, decreased in the liver of the 27-month-old rats. In the heart and the liver, the highest values of glutathione S-transferase were found at 5 months and 27 months, respectively. Glucose-6-phosphate dehydrogenase followed a similar trend in both heart and liver. Glutathione reductase also showed the same behaviour in heart and in liver, increasing in old rats with respect to the other age groups. A decrease in γ-glutamylcysteine synthetase was found in the heart and liver of 27-month-old rats in comparison with the 2-month-old ones. In conclusion, a decreased antioxidant capability has been demonstrated in both heart and liver of old rats.Key words: glutathione metabolism, age, rat heart, rat liver.

scholarly journals Aggravation of polycystic kidney disease in Han:SPRD rats by buthionine sulfoximine.

1997 ◽  
Vol 8 (8) ◽  
pp. 1283-1291 ◽  
Author(s):  
V E Torres ◽  
R J Bengal ◽  
R D Litwiller ◽  
D M Wilson
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Reduced Glutathione ◽  
Specific Inhibitor ◽  
Glutathione Depletion ◽  
Oxidized Glutathione ◽  
Cystic Disease ◽  
Polycystic Kidney ◽  
Redox Metabolism ◽  
Plasma Urea

The administration of ammonium chloride or of sodium or potassium bicarbonate has marked effects on the development of polycystic kidney disease (PKD) in Han:SPRD rats. Because of the possibility that these effects are mediated by changes in redox metabolism, the aim of this study was to determine whether depletion of glutathione, the most abundant and important cellular thiol and scavenger of reactive oxygen species, would affect the development of PKD in this animal model. +/+ and cy/+ Han:SPRD rats were treated with: (1) L-buthionine(S,R)-sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting enzyme for the synthesis of glutathione; (2) glutathione monoethyl ester (GME), a compound that is known to increase the intracellular levels of glutathione; or (3) BSO and GME. Treatment with these drugs was started at 3 wk of age, and the animals were killed at 6 or 8 wk of age. Renal levels of oxidized glutathione were significantly higher in cy/+ than in +/+ rats, whereas no significant differences in reduced glutathione were detected. The administration of BSO caused a marked reduction in the levels of glutathione. The administration of GME caused a significant increase in the levels of glutathione at 2 h, but not at 12 h, after the administration. The increase in the renal levels of glutathione 2 h after the administration of GME was less in the rats treated with BSO than in the rats not receiving this drug, indicating that in part the increase in glutathione level was due to de novo synthesis. BSO-induced glutathione depletion was accompanied by a marked aggravation of the renal cystic disease, as reflected by kidney weights, histological scores, and plasma urea concentrations. However, the administration of GME did not lessen the cystic disease and did not reverse the effects of BSO. The transient effect of GME administration and the simultaneous increases in the levels of cysteine and oxidized glutathione, in addition to reduced glutathione, may explain the lack of protection by GME. These data support the notion that changes in redox metabolism may affect the development of PKD.

scholarly journals Disruption of Redox Homeostasis by Enzymatic Activation of a Triakylphosphine Probe in Mitochondria

2019 ◽  
Author(s):  
Jade Nguyen ◽  
Alina Tirla ◽  
Pablo Rivera-Fuentes
Keyword(s):  
Cellular Response ◽  
Cell Function ◽  
Reduced Glutathione ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Confocal Imaging ◽  
Glutathione Metabolism ◽  
Oxidized Glutathione ◽  
Redox Stress ◽  
Fluorescent Reporter

Redox homeostasis is essential for cell function and its disruption is associated with cancer, metabolic and neurodegenerative diseases. Redox balance is largely regulated by the relative concentrations of reduced and oxidized glutathione. In eukaryotes, this ratio is different in each cell compartment, and disruption of the mitochondrial redox balance has been specifically linked to pathologies such as obesity and type II diabetes. Although reduced glutathione can be scavenged using electrophiles, there is a lack of probes that can produce it. In this study, we report an organellespecific reducing agent based on tributylphosphine that selectively reduces oxidized glutathione in mitochondria. This probe is activated by endogenous nitroreductases and subsequently releases tributylphosphine, as well as a fluorescent reporter, within the organelle. Confocal imaging and biological assays in human cells revealed that, counterintuitively, increased reduced glutathione induced oxidative stress through accumulation of superoxide. Transcriptomic analysis was used to establish that mitochondrial redox stress activates a cellular response orchestrated by transcription factor ATF4, which upregulates genes involved in glutathione metabolism.<br>

scholarly journals Disruption of Redox Homeostasis by Enzymatic Activation of a Triakylphosphine Probe in Mitochondria

2019 ◽  
Author(s):  
Jade Nguyen ◽  
Alina Tirla ◽  
Pablo Rivera-Fuentes
Keyword(s):  
Cellular Response ◽  
Cell Function ◽  
Reduced Glutathione ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Confocal Imaging ◽  
Glutathione Metabolism ◽  
Oxidized Glutathione ◽  
Redox Stress ◽  
Fluorescent Reporter

Redox homeostasis is essential for cell function and its disruption is associated with cancer, metabolic and neurodegenerative diseases. Redox balance is largely regulated by the relative concentrations of reduced and oxidized glutathione. In eukaryotes, this ratio is different in each cell compartment, and disruption of the mitochondrial redox balance has been specifically linked to pathologies such as obesity and type II diabetes. Although reduced glutathione can be scavenged using electrophiles, there is a lack of probes that can produce it. In this study, we report an organellespecific reducing agent based on tributylphosphine that selectively reduces oxidized glutathione in mitochondria. This probe is activated by endogenous nitroreductases and subsequently releases tributylphosphine, as well as a fluorescent reporter, within the organelle. Confocal imaging and biological assays in human cells revealed that, counterintuitively, increased reduced glutathione induced oxidative stress through accumulation of superoxide. Transcriptomic analysis was used to establish that mitochondrial redox stress activates a cellular response orchestrated by transcription factor ATF4, which upregulates genes involved in glutathione metabolism.<br>

scholarly journals Effect of Chronic Exposure to Pesticide Methomyl on Antioxidant Defense System in Testis of Tilapia (Oreochromis niloticus) and Its Recovery Pattern

2021 ◽  
Vol 11 (8) ◽  
pp. 3332
Author(s):  
Shunlong Meng ◽  
Xi Chen ◽  
Chao Song ◽  
Limin Fan ◽  
Liping Qiu ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Oxidative Damage ◽  
Glutathione Reductase ◽  
Oreochromis Niloticus ◽  
Reduced Glutathione ◽  
Free Water ◽  
Oxidized Glutathione ◽  
Glutathione S Transferase ◽  
Recovery Pattern

The chronic effect of environmental methomyl on the antioxidant system in testis of Nile tilapia (Oreochromis niloticus) and its recovery pattern was investigated. Tilapia were exposed to sublethal concentrations of 0.2, 2, 20 and 200 μgL−1 methomyl for 30 days and thereafter moved to methomyl-free water for 18 days. Antioxidant levels in testis, including glutathione peroxidase, catalase, glutathione-S-transferase, glutathione reductase, superoxide dismutase, reduced glutathione, oxidized glutathione were measured every 6 days during the period of exposure, and at 18 days after being transferred to methomyl-free water. The results showed that lower methomyl concentration (0.2 μgL−1) had no effect on the above antioxidants, thus 0.2 μgL−1 could be seen as NOAEL for methomyl to tilapia. However, higher methomyl concentration of 2, 20 and 200 μgL−1 could significantly influence the above antioxidants. Glutathione peroxidase and oxidized glutathione increased significantly. On the contrary, reduced glutathione decreased significantly. Catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase increased at lower methomyl (2 and 20 μgL−1), but decreased at higher methomyl (200 μgL−1). The recovery test showed that oxidative damage caused by lower methomyl of 2 and 20 μgL−1 was reversible, and oxidative damage caused by higher methomyl of 200 μgL−1 was irreversible within 18 days of recovery period.

scholarly journals Exposure to Ti4Al4V Titanium Alloy Leads to Redox Abnormalities, Oxidative Stress, and Oxidative Damage in Patients Treated for Mandible Fractures

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jan Borys ◽  
Mateusz Maciejczyk ◽  
Bożena Antonowicz ◽  
Adam Krętowski ◽  
Danuta Waszkiel ◽  
...  
Keyword(s):  
Titanium Alloy ◽  
Oxidative Damage ◽  
Activity Concentration ◽  
Maxillofacial Surgery ◽  
Redox Balance ◽  
Passive Layer ◽  
Oxidative Modification ◽  
Mandibular Fractures ◽  
Mandible Fractures ◽  
Increased Activity

Due to the high biotolerance, favourable mechanical properties, and osseointegration ability, titanium is the basic biomaterial used in maxillofacial surgery. The passive layer of titanium dioxide on the surface of the implant effectively provides anticorrosive properties, but it can be damaged, resulting in the release of titanium ions to the surrounding tissues. The aim of our work was to evaluate the influence of Ti6Al4V titanium alloy on redox balance and oxidative damage in the periosteum surrounding the titanium miniplates and screws as well as in plasma and erythrocytes of patients with mandibular fractures. The study included 31 previously implanted patients (aged 21–29) treated for mandibular fractures and 31 healthy controls. We have demonstrated increased activity/concentration of antioxidants both in the mandibular periosteum and plasma/erythrocytes of patients with titanium mandibular fixations. However, increased concentrations of the products of oxidative protein and lipid modifications were only observed in the periosteum of the study group patients. The correlation between the products of oxidative modification of the mandible and antioxidants in plasma/erythrocytes suggests a relationship between the increase of oxidative damage at the implantation site and central redox disorders in patients with titanium miniplates and screws.

scholarly journals Forming active recombinant enterokinase expressed in Escherichia coli

2020 ◽  
Vol 18 (3) ◽  
pp. 553-560
Author(s):  
Le Thi Thu Hong ◽  
Luong Kim Phuong ◽  
Trinh Thi Thu Hien ◽  
Nguyen Thi Mai Phuong ◽  
Truong Nam Hai ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Recombinant Protein ◽  
Light Chain ◽  
Reduced Glutathione ◽  
Recombinant Protein Expression ◽  
Initial Assessment ◽  
Oxidized Glutathione ◽  
Expression Systems ◽  
Insoluble Form ◽  
Glutathione Oxidation

Enterokinase is a serine protease commonly used in some biotechnology researches. For these purposes, the light chain containing enterokinase activity has usually been expressed as recombinant protein in different expression systems because natural enterokinase extraction is often ineffective. In this study, we examined the formation of recombinant enterokinase expressed in Escherichia coli with biological activity. The thioredoxin-enterokinase (trx-ent) fusion protein was autocleavaged into thioredoxin and enterokinase when expressed under insoluble form, denatured with guanidine and then refolded with suitable oxidation and reduction steps. Meanwhile, soluble expression as well as insoluble form denatured by urea had not enzymatic activity. Denaturant solution of 6 M guanidine along with the re-folding conditions in oxidized glutathione oxidation buffers followed by the reduced glutathione buffer with arginine was applied to produce trx-ent protein capable of self-cleavage. The recombinant light-chain enterokinase protein had a size of about 35 kDa on the Tris-glycine gel. Initial assessment on substance had shown that enterokinase was capable of cleaving thioredoxin-sumoprotease into thioredoxin and sumoprotease. This result provides the base for the production of active recombinant enterokinase to be used in recombinant protein expression technology.

scholarly journals Coordination chemistry of glutathione.

1999 ◽  
Vol 46 (3) ◽  
pp. 567-580 ◽  
Author(s):  
A Krezel ◽  
W Bal
Keyword(s):  
Glutamic Acid ◽  
Metal Ions ◽  
Metal Ion ◽  
Reduced Glutathione ◽  
Transition Metal Ions ◽  
Oxidized Glutathione ◽  
Binding Modes ◽  
Glutamic Acid Residue ◽  
Reduced And Oxidized Glutathione ◽  
Soft Metal

The metal ion coordination abilities of reduced and oxidized glutathione are reviewed. Reduced glutathione (GSH) is a very versatile ligand, forming stable complexes with both hard and soft metal ions. Several general binding modes of GSH are described. Soft metal ions coordinate exclusively or primarily through thiol sulfur. Hard ones prefer the amino acid-like moiety of the glutamic acid residue. Several transition metal ions can additionally coordinate to the peptide nitrogen of the gamma-Glu-Cys bond. Oxidized glutathione lacks the thiol function. Nevertheless, it proves to be a surprisingly efficient ligand for a range of metal ions, coordinating them primarily through the donors of the glutamic acid residue.

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