Protein glutathionylation and oxidative stress

Niwa, Toshimitsu

doi:10.1016/j.jchromb.2006.12.029

Cited by 51 publications

(55 citation statements)

References 47 publications

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“…Similarly, no evaluation of the influence of genetic polymorphism of GST or personal habit (i.e., cigarette smoking) on this recently introduced biomarker has been done to our knowledge. On the other hand, a number of studies have been recently done to evaluate the levels of GSS-Hb in diseases in which an oxidative stress is believed to play a role (34,35). Our data, for the first time, show that exposure to chemicals may also modify this biological index in agreement with similar modifications observed following a condition of oxidative stress.…”

Section: Discussionsupporting

confidence: 86%

Glutathione Transferases and Glutathionylated Hemoglobin in Workers Exposed to Low Doses of 1,3-Butadiene

Primavera

Fustinoni

Biroccio

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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We evaluated glutathione transferase (GST) activities and the levels of glutathionylated hemoglobin in the RBC of 42 workers exposed to 1,3-butadiene in a petrochemical plant, using 43 workers not exposed to 1,3-butadiene and 82 foresters as internal and external controls, respectively. Median 1,3-butadiene exposure levels were 1.5, 0.4, and 0.1 Mg/m 3 in 1,3-butadieneexposed workers, in workers not directly exposed to 1,3-butadiene, and in foresters, respectively. In addition, we determined in the peripheral blood lymphocytes of the same individuals the presence of GST polymorphic genes GSTT1 and GSTM1 and the distribution of GSTP1 allelic variants. Comparing the mean values observed in petrochemical workers with those of control foresters, we found a marked decrease of GST enzymatic activity and a significant increase of glutathionylated hemoglobin in the petrochemical workers. A weak but significant negative correlation was found between levels of 1,3-butadiene exposure and GST activity, whereas a positive correlation was found between 1,3-butadiene exposure and glutathionylated hemoglobin. A negative correlation was also observed between GST activity and glutathionylated hemoglobin. No influence of confounders was observed. Using a multiple linear regression model, up to 50.6% and 41.9% of the variability observed in glutathionylated hemoglobin and GST activity, respectively, were explained by 1,3-butadiene exposure, working setting, and GSTT1 genotype. These results indicate that occupational exposure to 1,3-butadiene induces an oxidative stress that impairs the GST balance in RBC, and suggest that GST activity and glutathionylated hemoglobin could be recommended as promising biomarkers of effect in petrochemical workers. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3004 -12)

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Section: Discussionsupporting

confidence: 86%

Glutathione Transferases and Glutathionylated Hemoglobin in Workers Exposed to Low Doses of 1,3-Butadiene

Primavera

Fustinoni

Biroccio

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Beyond its antioxidant role, emerging concepts implicated GSH in the regulation of cell signaling by reversible glutathionylation of proteins (like actin, Ras, caspase, NFB, and thioredoxin) (25)(26)(27)(28), yet the successful isolation of ␥-GCS knock-out cells in the presence of exogenous GSH or NAC raised uncertainties about the supposedly unique role of GSH in cell physiology, even though the knock-out of ␥-GCS is embryonically lethal in mice (9). Our cellular studies demonstrate for the first time that cellular GSH deficiency can be rescued by an alternative redox system, the (Cys) 2 /Cys redox cycle, characterized by increased cystine uptake, intracellular cystine reduction, and augmented intracellular and highly elevated extracellular Cys levels.…”

Section: Discussionmentioning

confidence: 99%

System xc− and Thioredoxin Reductase 1 Cooperatively Rescue Glutathione Deficiency

Mandal

Seiler

Perisic

et al. 2010

Journal of Biological Chemistry

216

161

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GSH is the major antioxidant and detoxifier of xenobiotics in mammalian cells. A strong decrease of intracellular GSH has been frequently linked to pathological conditions like ischemia/ reperfusion injury and degenerative diseases including diabetes, atherosclerosis, and neurodegeneration. Although GSH is essential for survival, the deleterious effects of GSH deficiency can often be compensated by thiol-containing antioxidants. Using three genetically defined cellular systems, we show here that forced expression of xCT, the substrate-specific subunit of the cystine/glutamate antiporter, in ␥-glutamylcysteine synthetase knock-out cells rescues GSH deficiency by increasing cellular cystine uptake, leading to augmented intracellular and surprisingly high extracellular cysteine levels. Moreover, we provide evidence that under GSH deprivation, the cytosolic thioredoxin/thioredoxin reductase system plays an essential role for the cells to deal with the excess amount of intracellular cystine. Our studies provide first evidence that GSH deficiency can be rescued by an intrinsic genetic mechanism to be considered when designing therapeutic rationales targeting specific redox enzymes to combat diseases linked to GSH deprivation.

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“…35 Glutathiolation is a reversible posttranslational modification that occurs by direct interaction of protein-SH with GSH under oxidizing conditions, by thiol disulfide exchange between a protein-SH and GSSG, or by reaction of protein-SH with S-nitrosoglutathione. 36 To date, no specific glutathiolated plasma proteins have been reported; however, glutathiolation has been demonstrated for the intracellular forms of 1-Cys peroxiredoxins (Prx), Trxs, and Grxs and other cellular proteins, 37,38 such as RAS and SERCA. [39][40][41] …”

Section: Glutathione (Gsh)mentioning

confidence: 99%

Redox Regulation in the Extracellular Environment

Ottaviano

Handy

Loscalzo

2008

Circ J

128

100

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Molecular oxygen is involved in the oxidation of substrates used to produce energy; however, normal metabolism can also generate harmful (bio)chemical byproducts. These deleterious products are partially reduced forms of oxygen, and include free radicals such as superoxide anion radical, hydroxyl radical, or highly oxidizing non-radical species such as hydrogen peroxide (H2O2) and lipid peroxides, which are collectively known as ROS. 1 ROS typically derive from normal metabolism, activated leukocytes, and ambient oxygen in the environment. The production and accumulation of ROS and their downstream effects can be controlled or attenuated by antioxidants. When the ability of antioxidants to eliminate harmful cellular and extracellular ROS is compromised, the balance between ROS generation and antioxidant function to eliminate ROS is shifted in favor of an accumulation of oxidants, which defines the state of oxidative stress in a cell or organism. Oxidative damage can affect DNA, lipids, and proteins, and eventually compromise cell integrity. Many studies have implicated ROS in the pathological processes leading to heart disease, cancer, aging, AIDS, and inflammatory and autoimmune diseases.Oxidants, especially free radicals, are highly reactive. Superoxide can react within milliseconds with nitric oxide (NO) to produce peroxynitrite (ONOO -), a reactive nitrogen species (RNS). The nitrosium cation and nitroxyl anion are other RNS derived from NO. 2 Peroxynitrite is a strong oxidant involved in the nitrosative modification of proteins and lipids. Owing to its rapid reaction with NO, superoxide may modulate NO bioavailability and, subsequently, regulate vascular function. 3 Circulation Journal Vol.72, January 2008The cytosol, mitochondria, peroxisomes, and plasma are all potential sites of ROS formation. 4 The major sources of ROS are enzymatic via nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), xanthine oxidase, myeloperoxidase, endothelial NO synthase (eNOS), or as a consequence of normal mitochondrial respiration. In vascular cells, other enzymatic sources of ROS include cytochrome P450 isoenzymes, lipoxygenase, cyclooxygenase, heme oxygenase, and glucose oxidase. 1,3,[5][6][7] Most reviews to date have focused on the role of intracellular antioxidants that eliminate ROS from the intracellular environment. There are, however, several extracellular antioxidants that also play an equally important role in limiting ROS accumulation in the extracellular environment. Along with limiting ROS accumulation, extracellular redox status is essential for maintaining protein stability and function.The major enzymes important for the elimination of extracellular H2O2 are glutathione peroxidase-3 (GPx-3) and peroxiredoxin IV (Prx IV). Other extracellular antioxidants involved in ROS elimination include paraoxonase (PON), thioredoxin (Trx), Trx reductase (TrxR), glutaredoxin (Grx), extracellular superoxide dismutase (EC-SOD), and extracellular glutathione (GSH).Some of these antioxidants, notably glutathione...

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Protein glutathionylation and oxidative stress

Cited by 51 publications

References 47 publications

Glutathione Transferases and Glutathionylated Hemoglobin in Workers Exposed to Low Doses of 1,3-Butadiene

Glutathione Transferases and Glutathionylated Hemoglobin in Workers Exposed to Low Doses of 1,3-Butadiene

System xc− and Thioredoxin Reductase 1 Cooperatively Rescue Glutathione Deficiency

Redox Regulation in the Extracellular Environment

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