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Biomedicine & Pharmacotherapy =... Jul 2014Throughout the last couple decades, the cause and consequences of substance abuse has expanded to identify the underlying neurobiological signaling mechanisms associated... (Review)
Review
Throughout the last couple decades, the cause and consequences of substance abuse has expanded to identify the underlying neurobiological signaling mechanisms associated with addictive behavior. Chronic use of drugs, such as cocaine, methamphetamine and alcohol leads to the formation of oxidative or nitrosative stress (ROS/RNS) and changes in glutathione and redox homeostasis. Of importance, redox-sensitive post-translational modifications on cysteine residues, such as S-glutathionylation and S-nitrosylation could impact on the structure and function of addiction related signaling proteins. In this commentary, we evaluate the role of glutathione and redox signaling in cocaine-, methamphetamine- and alcohol addiction and conclude by discussing the possibility of targeting redox pathways for the therapeutic intervention of these substance abuse disorders.
Topics: Animals; Glutathione; Humans; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Substance-Related Disorders
PubMed: 25027386
DOI: 10.1016/j.biopha.2014.06.001 -
Journal of Physiology and Pharmacology... Jun 2016The risk of developing chronic hypertension increases with age. Among others factors, increased oxidative stress is a well-recognized etiological factor for the... (Review)
Review
The risk of developing chronic hypertension increases with age. Among others factors, increased oxidative stress is a well-recognized etiological factor for the development of hypertension. The co-occurrence of oxidative stress and hypertension may occur as a consequence of a decrease in antioxidant defense system activity or elevated reactive oxygen species generation. Glutathione is a major intracellular thiol-disulfide redox buffer that serves as a cofactor for many antioxidant enzymes. Glutathione-related parameters are altered in hypertension, suggesting that there is an association between the glutathione-related redox system and hypertension. In this review, we provide mechanistic explanations for how glutathione maintains blood pressure. More specifically, we discuss glutathione's role in combating oxidative stress and maintaining nitric oxide bioavailability via the formation of nitrosothiols and nitrosohemoglobin. Although impaired vasodilator responses are observed in S-nitrosothiol-deficient red blood cells, this potential hypertensive mechanism is currently overlooked in the literature. Here we fill in this gap by discussing the role of glutathione in nitric oxide metabolism and controlling blood pressure. We conclude that disturbances in glutathione metabolism might explain age-dependent increases in blood pressure.
Topics: Animals; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Hypertension; Nitric Oxide; Oxidative Stress; Vasodilation
PubMed: 27511994
DOI: No ID Found -
Food Chemistry Aug 2022A fast, sensitive and reproducible method using LC-MS/MS for simultaneous quantification of glutathione (GSH), glutathione disulfide (GSSG) and glutathione-S-sulfonate...
A fast, sensitive and reproducible method using LC-MS/MS for simultaneous quantification of glutathione (GSH), glutathione disulfide (GSSG) and glutathione-S-sulfonate (GSSOH) was developed, optimised and applied in analysis of grape juice and wine samples. The results show that only GSH (10-60 mg·L) and GSSG (2-11 mg·L) are found in grape juice when SO is not added. GSSOH was detected in must samples treated with SO but only at a low concentration (<1 mg L). In the wine samples, the dominant form of glutathione was GSSOH (5-11 mg L), followed by GSH (0-5 mg L) and GSSG (0-6 mg L), underscoring the importance of GSSOH quantification. GSSOH formation in wine was correlated with the total SO level in the wine. We believe this is the first report on GSSOH quantification in wine.
Topics: Chromatography, Liquid; Glutathione; Glutathione Disulfide; Tandem Mass Spectrometry; Vitis; Wine
PubMed: 35509159
DOI: 10.1016/j.foodchem.2022.132756 -
Histochemistry and Cell Biology Sep 2022Plant ascorbate and glutathione metabolism counteracts oxidative stress mediated, for example, by excess light. In this review, we discuss the properties of... (Review)
Review
Plant ascorbate and glutathione metabolism counteracts oxidative stress mediated, for example, by excess light. In this review, we discuss the properties of immunocytochemistry and transmission electron microscopy, redox-sensitive dyes or probes and bright-field microscopy, confocal microscopy or fluorescence microscopy for the visualization and quantification of glutathione at the cellular or subcellular level in plants and the quantification of glutathione from isolated organelles. In previous studies, we showed that subcellular ascorbate and glutathione levels in Arabidopsis are affected by high light stress. The use of light-emitting diodes (LEDs) is gaining increasing importance in growing indoor crops and ornamental plants. A combination of different LED types allows custom-made combinations of wavelengths and prevents damage related to high photon flux rates. In this review we provide an overview on how different light spectra and light intensities affect glutathione metabolism at the cellular and subcellular levels in plants. Findings obtained in our most recent study demonstrate that both light intensity and spectrum significantly affected glutathione metabolism in wheat at the transcriptional level and caused genotype-specific reactions in the investigated Arabidopsis lines.
Topics: Arabidopsis; Ascorbic Acid; Glutathione; Organelles; Oxidation-Reduction; Plants
PubMed: 35486180
DOI: 10.1007/s00418-022-02103-2 -
The Journal of Biological Chemistry Nov 2020Persulfides (RSSH/RSS) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (HS). Despite...
Persulfides (RSSH/RSS) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (HS). Despite their growing relevance, their chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/GSS), the derivative of the abundant cellular thiol glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and HS. A p of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically relevant electrophiles peroxynitrite and hydrogen peroxide, and with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through S2 mechanisms. At neutral pH, GSSH reacted faster than GSH because of increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called α effect, the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the α effect correlated with the Brønsted nucleophilic factor, β, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the p of a biological persulfide and the first examination of the α effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Disulfides; Glutathione; Hydrogen Peroxide; Hydrogen Sulfide; Hydrogen-Ion Concentration; Kinetics; Peroxynitrous Acid; Quantum Theory; Tandem Mass Spectrometry; Thermodynamics
PubMed: 32873707
DOI: 10.1074/jbc.RA120.014728 -
Nature Communications Jul 2017Glutathione plays many important roles in biological processes; however, the dynamic changes of glutathione concentrations in living cells remain largely unknown. Here,...
Glutathione plays many important roles in biological processes; however, the dynamic changes of glutathione concentrations in living cells remain largely unknown. Here, we report a reversible reaction-based fluorescent probe-designated as RealThiol (RT)-that can quantitatively monitor the real-time glutathione dynamics in living cells. Using RT, we observe enhanced antioxidant capability of activated neurons and dynamic glutathione changes during ferroptosis. RT is thus a versatile tool that can be used for both confocal microscopy and flow cytometry based high-throughput quantification of glutathione levels in single cells. We envision that this new glutathione probe will enable opportunities to study glutathione dynamics and transportation and expand our understanding of the physiological and pathological roles of glutathione in living cells.
Topics: Fluorescent Dyes; Fluorometry; Glutathione; HeLa Cells; Humans; Kinetics; Single-Cell Analysis
PubMed: 28703127
DOI: 10.1038/ncomms16087 -
Molecules (Basel, Switzerland) May 2021Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts...
Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC-MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups.
Topics: Antioxidants; Disulfides; Gas Chromatography-Mass Spectrometry; Glutathione; Glutathione Disulfide; Magnetic Resonance Spectroscopy; Oxidation-Reduction; Oxidative Stress; Phosphates; Sulfhydryl Compounds
PubMed: 34067789
DOI: 10.3390/molecules26102973 -
PloS One 2019The effects of various light intensities and spectral compositions on glutathione and amino acid metabolism were compared in wheat. Increase of light intensity...
The effects of various light intensities and spectral compositions on glutathione and amino acid metabolism were compared in wheat. Increase of light intensity (low-normal-high) was accompanied by a simultaneous increase in the shoot fresh weight, photosynthetic activity and glutathione content. These parameters were also affected by the modification of the ratios of blue, red and far-red components (referred to as blue, pink and far-red lights) compared to normal white light. The photosynthetic activity and the glutathione content decreased to 50% and the percentage of glutathione disulfide (characterising the redox state of the tissues) in the total glutathione pool doubled in far-red light. The alterations in the level and redox state of the antioxidant glutathione resulted from the effect of light on its synthesis as it could be concluded from the changes in the transcription of the related genes. Modification of the light conditions also greatly affected both the amount and the ratio of free amino acids. The total free amino acid content was greatly induced by the increase of light intensity and was greatly reduced in pink light compared to the normal intensity white light. The concentrations of most amino acids were similarly affected by the light conditions as described for the total free amino acid content but Pro, Met, Thr, ornithine and cystathionine showed unique response to light. As observed for the amino acid levels, the expression of several genes involved in their metabolism also enhanced due to increased light intensity. Interestingly, the modification of the spectrum greatly inhibited the expression of most of these genes. Correlation analysis of the investigated parameters indicates that changes in the light conditions may affect growth through the adjustment of photosynthesis and the glutathione-dependent redox state of the tissues. This process modifies the metabolism of glutathione and amino acids at transcriptional level.
Topics: Amino Acids; Glutathione; Light; Photosynthesis; Triticum
PubMed: 31891631
DOI: 10.1371/journal.pone.0227271 -
Biomedical Chromatography : BMC Jan 2010The ability to conduct validated analyses of glutathione (GSH)-adducts and their metabolites is critically important in order to establish whether they play a role in... (Review)
Review
The ability to conduct validated analyses of glutathione (GSH)-adducts and their metabolites is critically important in order to establish whether they play a role in cellular biochemical or pathophysiological processes. The use of stable isotope dilution (SID) methodology in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides the highest bioanalytical specificity possible for such analyses. Quantitative studies normally require the high sensitivity that can be obtained by the use of multiple reaction monitoring (MRM)/MS rather than the much less sensitive but more specific full scanning methodology. The method employs a parent ion corresponding to the intact molecule together with a prominent product ion that obtained by collision induced dissociation. Using SID LC-MRM/MS, analytes must have the same relative LC retention time to the heavy isotope internal standard established during the validation procedure, the correct parent ion and the correct product ion. This level of specificity cannot be attained with any other bioanalytical technique employed for biomarker analysis. This review will describe the application of SID LC-MR/MS methodology for the analysis of GSH-adducts and their metabolites. It will also discuss potential future directions for the use of this methodology for rigorous determination of their utility as disease and exposure biomarkers.
Topics: Animals; Chromatography, Liquid; Glutathione; Humans; Tandem Mass Spectrometry
PubMed: 20017120
DOI: 10.1002/bmc.1374 -
Oxidative Medicine and Cellular... 2013Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH... (Review)
Review
Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH homeostasis are involved in the etiology and progression of many human diseases including cancer. While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells. The present review highlights the role of GSH and related cytoprotective effects in the susceptibility to carcinogenesis and in the sensitivity of tumors to the cytotoxic effects of anticancer agents.
Topics: Animals; Disease Progression; Drug Resistance, Neoplasm; Glutathione; Humans; Neoplasms
PubMed: 23766865
DOI: 10.1155/2013/972913