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Special Issue "Sulfur Atom: Element for Adaptation to an Oxidative Environment"

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Molecular Diversity".

Deadline for manuscript submissions: closed (31 October 2014)

Special Issue Editors

Guest Editor
Dr. Noriyuki Nagahara

Isotope Research Center, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
Interests: stress; oxygen atoms; oxidation and reduction; persulfide; protein function; redox chemistry; sulfane sulfur atoms; sulfur atoms; sulfur compounds; sulfurtransferase
Guest Editor
Dr. Maria Wrobel (Website)

Chair of Medical Biochemistry,Kopernika, Jagiellonian University Medical College, 7 St., 31-034 Kraków, Poland

Special Issue Information

Dear Colleagues,

During the rise of oxygen concentration in the earth’s atmosphere, a sulfur atom is incorporated into proteins as the redox-active cysteine residue, and antioxidant molecules, such as thioredoxin, glutathione, and glutaredoxin appear. Cysteine residues in proteins first form intra- and inter-molecular disulfides to maintain protein (peptide) structure and also to regulate protein function. Secondly, the redox-active cysteine residues are known to regulate proteins redox state and function by reversible oxidation to cysteinosulfenic or cysteinosulfinic residues or by -SH group sulfuration to persulfides. Finally, cysteine residues of catalytic sites of such enzymes as sulfurtransferases and sulfotransferases, contributing to the transfer of elemental sulfur and sulfenate, respectively, are involved in sulfur metabolism. Recently, sulfur atoms, at reduced oxidation state, of hydrogen sulfide and polysulfides have been recognized as important molecules in the regulation of many physiological processes. The Editors’ intent is to collect both review and original papers on the above subjects in a special issue.

Dr. Noriyuki Nagahara
Dr. Maria Wrobel
Guest Editors

Submission

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Keywords

  • cysteine metabolism
  • hydrogen sulfide
  • oxidative stress
  • oxygen atoms; oxidation
  • persulfide
  • protein function
  • redox chemistry
  • reduction
  • sulfane sulfur atoms
  • sulfur atoms
  • sulfur compounds
  • sulfurtransferases

Related Special Issue

Published Papers (11 papers)

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Research

Jump to: Review

Open AccessArticle Glutathione-Garlic Sulfur Conjugates: Slow Hydrogen Sulfide Releasing Agents for Therapeutic Applications
Molecules 2015, 20(1), 1731-1750; doi:10.3390/molecules20011731
Received: 13 December 2014 / Revised: 31 December 2014 / Accepted: 13 January 2015 / Published: 20 January 2015
Cited by 6 | PDF Full-text (2121 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit [...] Read more.
Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H2S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H2S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
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Open AccessArticle Is Development of High-Grade Gliomas Sulfur-Dependent?
Molecules 2014, 19(12), 21350-21362; doi:10.3390/molecules191221350
Received: 2 November 2014 / Revised: 4 December 2014 / Accepted: 12 December 2014 / Published: 19 December 2014
PDF Full-text (748 KB) | HTML Full-text | XML Full-text
Abstract
We characterized γ-cystathionase, rhodanese and 3-mercaptopyruvate sulfurtransferase activities in various regions of human brain (the cortex, thalamus, hypothalamus, hippocampus, cerebellum and subcortical nuclei) and human gliomas with II to IV grade of malignancy (according to the WHO classification). The human brain regions, [...] Read more.
We characterized γ-cystathionase, rhodanese and 3-mercaptopyruvate sulfurtransferase activities in various regions of human brain (the cortex, thalamus, hypothalamus, hippocampus, cerebellum and subcortical nuclei) and human gliomas with II to IV grade of malignancy (according to the WHO classification). The human brain regions, as compared to human liver, showed low γ-cystathionase activity. The activity of rhodanese was also much lower and it did not vary significantly between the investigated brain regions. The activity of 3-mercaptopyruvate sulfurtransferase was the highest in the thalamus, hypothalamus and subcortical nuclei and essentially the same level of sulfane sulfur was found in all the investigated brain regions. The investigations demonstrated that the level of sulfane sulfur in gliomas with the highest grades was high in comparison to various human brain regions, and was correlated with a decreased activity of γ-cystathionase, 3-mercaptopyruvate sulfurtransferase and rhodanese. This can suggest sulfane sulfur accumulation and points to its importance for malignant cell proliferation and tumor growth. In gliomas with the highest grades of malignancy, despite decreased levels of total free cysteine and total free glutathione, a high ratio of GSH/GSSG was maintained, which is important for the process of malignant cells proliferation. A high level of sulfane sulfur and high GSH/GSSG ratio could result in the elevated hydrogen sulfide levels. Because of the disappearance of γ-cystathionase activity in high-grade gliomas, it seems to be possible that 3-mercaptopyruvate sulfurtransferase could participate in hydrogen sulfide production. The results confirm sulfur dependence of malignant brain tumors. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessArticle Crystallographic Studies Evidencing the High Energy Tolerance to Disrupting the Interface Disulfide Bond of Thioredoxin 1 from White Leg Shrimp Litopenaeus vannamei
Molecules 2014, 19(12), 21113-21126; doi:10.3390/molecules191221113
Received: 10 October 2014 / Revised: 6 December 2014 / Accepted: 9 December 2014 / Published: 15 December 2014
PDF Full-text (1669 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Thioredoxin (Trx) is a small 12-kDa redox protein that catalyzes the reduction of disulfide bonds in proteins from different biological systems. A recent study of the crystal structure of white leg shrimp thioredoxin 1 from Litopenaeus vannamei (LvTrx) revealed a [...] Read more.
Thioredoxin (Trx) is a small 12-kDa redox protein that catalyzes the reduction of disulfide bonds in proteins from different biological systems. A recent study of the crystal structure of white leg shrimp thioredoxin 1 from Litopenaeus vannamei (LvTrx) revealed a dimeric form of the protein mediated by a covalent link through a disulfide bond between Cys73 from each monomer. In the present study, X-ray-induced damage in the catalytic and the interface disulfide bond of LvTrx was studied at atomic resolution at different transmission energies of 8% and 27%, 12.8 keV at 100 K in the beamline I-24 at Diamond Light Source. We found that at an absorbed dose of 32 MGy, the X-ray induces the cleavage of the disulfide bond of each catalytic site; however, the interface disulfide bond was cleaved at an X-ray adsorbed dose of 85 MGy; despite being the most solvent-exposed disulfide bond in LvTrx (~50 Å2). This result clearly established that the interface disulfide bond is very stable and, therefore, less susceptible to being reduced by X-rays. In fact, these studies open the possibility of the existence in solution of a dimeric LvTrx. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)

Review

Jump to: Research

Open AccessReview Tyrosine Sulfation as a Protein Post-Translational Modification
Molecules 2015, 20(2), 2138-2164; doi:10.3390/molecules20022138
Received: 6 November 2014 / Revised: 6 January 2015 / Accepted: 14 January 2015 / Published: 28 January 2015
Cited by 6 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text
Abstract
Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. [...] Read more.
Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However, the significance of PTS under physiological conditions and its link to diseases have just begun to be appreciated in recent years. PTS is catalyzed by tyrosylprotein sulfotransferase (TPST) through transfer of an activated sulfate from 3'-phosphoadenosine-5'-phosphosulfate to tyrosine in a variety of proteins and peptides. Currently, only a small fraction of sulfated proteins is known and the understanding of the biological sulfation mechanisms is still in progress. In this review, we give an introductory and selective brief review of PTS and then summarize the basic biochemical information including the activity and the preparation of TPST, methods for the determination of PTS, and kinetics and reaction mechanism of TPST. This information is fundamental for the further exploration of the function of PTS that induces protein-protein interactions and the subsequent biochemical and physiological reactions. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview Glutathionylspermidine in the Modification of Protein SH Groups: The Enzymology and Its Application to Study Protein Glutathionylation
Molecules 2015, 20(1), 1452-1474; doi:10.3390/molecules20011452
Received: 30 September 2014 / Accepted: 15 December 2014 / Published: 15 January 2015
Cited by 1 | PDF Full-text (2129 KB) | HTML Full-text | XML Full-text
Abstract
Cysteine is very susceptible to reactive oxygen species. In response; posttranslational thiol modifications such as reversible disulfide bond formation have arisen as protective mechanisms against undesired in vivo cysteine oxidation. In Gram-negative bacteria a major defense mechanism against cysteine overoxidation is the [...] Read more.
Cysteine is very susceptible to reactive oxygen species. In response; posttranslational thiol modifications such as reversible disulfide bond formation have arisen as protective mechanisms against undesired in vivo cysteine oxidation. In Gram-negative bacteria a major defense mechanism against cysteine overoxidation is the formation of mixed protein disulfides with low molecular weight thiols such as glutathione and glutathionylspermidine. In this review we discuss some of the mechanistic aspects of glutathionylspermidine in prokaryotes and extend its potential use to eukaryotes in proteomics and biochemical applications through an example with tissue transglutaminase and its S-glutathionylation. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview Possible Roles of Plant Sulfurtransferases in Detoxification of Cyanide, Reactive Oxygen Species, Selected Heavy Metals and Arsenate
Molecules 2015, 20(1), 1410-1423; doi:10.3390/molecules20011410
Received: 10 November 2014 / Accepted: 9 January 2015 / Published: 14 January 2015
Cited by 2 | PDF Full-text (1050 KB) | HTML Full-text | XML Full-text
Abstract
Plants and animals have evolved various potential mechanisms to surmount the adverse effects of heavy metal toxicity. Plants possess low molecular weight compounds containing sulfhydryl groups (-SH) that actively react with toxic metals. For instance, glutathione (γ-Glu-Cys-Gly) is a sulfur-containing tripeptide thiol [...] Read more.
Plants and animals have evolved various potential mechanisms to surmount the adverse effects of heavy metal toxicity. Plants possess low molecular weight compounds containing sulfhydryl groups (-SH) that actively react with toxic metals. For instance, glutathione (γ-Glu-Cys-Gly) is a sulfur-containing tripeptide thiol and a substrate of cysteine-rich phytochelatins (γ-Glu-Cys)2–11-Gly (PCs). Phytochelatins react with heavy metal ions by glutathione S-transferase in the cytosol and afterwards they are sequestered into the vacuole for degradation. Furthermore, heavy metals induce reactive oxygen species (ROS), which directly or indirectly influence metabolic processes. Reduced glutathione (GSH) attributes as an antioxidant and participates to control ROS during stress. Maintenance of the GSH/GSSG ratio is important for cellular redox balance, which is crucial for the survival of the plants. In this context, sulfurtransferases (Str), also called rhodaneses, comprise a group of enzymes widely distributed in all phyla, paving the way for the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors, at least in vitro. The best characterized in vitro reaction is the transfer of a sulfane sulfur atom from thiosulfate to cyanide, leading to the formation of sulfite and thiocyanate. Plants as well as other organisms have multi-protein families (MPF) of Str. Despite the presence of Str activities in many living organisms, their physiological role has not been clarified unambiguously. In mammals, these proteins are involved in the elimination of cyanide released from cyanogenic compounds. However, their ubiquity suggests additional physiological functions. Furthermore, it is speculated that a member of the Str family acts as arsenate reductase (AR) and is involved in arsenate detoxification. In summary, the role of Str in detoxification processes is still not well understood but seems to be a major function in the organism. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview Hydrogen Sulfide and Endothelium-Dependent Vasorelaxation
Molecules 2014, 19(12), 21183-21199; doi:10.3390/molecules191221183
Received: 10 November 2014 / Revised: 9 December 2014 / Accepted: 9 December 2014 / Published: 16 December 2014
Cited by 11 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
In addition to nitric oxide and carbon monoxide, hydrogen sulfide (H2S), synthesized enzymatically from l-cysteine or l-homocysteine, is the third gasotransmitter in mammals. Endogenous H2S is involved in the regulation of many physiological processes, including vascular tone. Although [...] Read more.
In addition to nitric oxide and carbon monoxide, hydrogen sulfide (H2S), synthesized enzymatically from l-cysteine or l-homocysteine, is the third gasotransmitter in mammals. Endogenous H2S is involved in the regulation of many physiological processes, including vascular tone. Although initially it was suggested that in the vascular wall H2S is synthesized only by smooth muscle cells and relaxes them by activating ATP-sensitive potassium channels, more recent studies indicate that H2S is synthesized in endothelial cells as well. Endothelial H2S production is stimulated by many factors, including acetylcholine, shear stress, adipose tissue hormone leptin, estrogens and plant flavonoids. In some vascular preparations H2S plays a role of endothelium-derived hyperpolarizing factor by activating small and intermediate-conductance calcium-activated potassium channels. Endothelial H2S signaling is up-regulated in some pathologies, such as obesity and cerebral ischemia-reperfusion. In addition, H2S activates endothelial NO synthase and inhibits cGMP degradation by phosphodiesterase 5 thus potentiating the effect of NO-cGMP pathway. Moreover, H2S-derived polysulfides directly activate protein kinase G. Finally, H2S interacts with NO to form nitroxyl (HNO)—a potent vasorelaxant. H2S appears to play an important and multidimensional role in endothelium-dependent vasorelaxation. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview Potential Role of Sulfur-Containing Antioxidant Systems in Highly Oxidative Environments
Molecules 2014, 19(12), 19376-19389; doi:10.3390/molecules191219376
Received: 25 August 2014 / Revised: 11 November 2014 / Accepted: 14 November 2014 / Published: 25 November 2014
Cited by 2 | PDF Full-text (253 KB) | HTML Full-text | XML Full-text
Abstract
All forms of life maintain a reducing environment (homeostasis) within their cells. Perturbations in the normal redox state can lead to an oxidative environment which has deleterious effects, especially in health. In biological systems, metabolic activities are dependent mainly on mitochondrial oxidative [...] Read more.
All forms of life maintain a reducing environment (homeostasis) within their cells. Perturbations in the normal redox state can lead to an oxidative environment which has deleterious effects, especially in health. In biological systems, metabolic activities are dependent mainly on mitochondrial oxidative phosphorylation, a metabolic pathway that uses energy released by the oxidation of nutrients to produce ATP. In the process of oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors such as oxygen in redox reactions and often results to the generation of reactive species. Reactive oxygen species consist of a class of radical and non-radical oxygen derivatives. The imbalance between the reactive oxygen species and antioxidant defence systems leads to oxidative burden and hence, damage biological molecules. Antioxidants help to prevent or fix the deleterious effects of reactive species. Sulfur is an important element in biological systems. This atom is usually integrated into proteins as the redox-active cysteine residue and in molecules such as glutathione, thioredoxin and glutaredoxin which are vital antioxidant molecules and are therefore essential for life. This review covers the role of sulfur containing antioxidant systems in oxidative environments. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview Hydrogen Sulfide and Polysulfides as Biological Mediators
Molecules 2014, 19(10), 16146-16157; doi:10.3390/molecules191016146
Received: 16 September 2014 / Revised: 30 September 2014 / Accepted: 8 October 2014 / Published: 9 October 2014
Cited by 26 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogen sulfide (H2S) is recognized as a biological mediator with various roles such as neuromodulation, regulation of the vascular tone, cytoprotection, anti-inflammation, oxygen sensing, angiogenesis, and generation of mitochondrial energy. It is produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), [...] Read more.
Hydrogen sulfide (H2S) is recognized as a biological mediator with various roles such as neuromodulation, regulation of the vascular tone, cytoprotection, anti-inflammation, oxygen sensing, angiogenesis, and generation of mitochondrial energy. It is produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST). The activity of CBS is enhanced by S-adenosyl methionine (SAM) and glutathionylation, while it is inhibited by nitric oxide (NO) and carbon monoxide (CO). The activity of CSE and cysteine aminotransferase (CAT), which produces the 3MST substrate 3-mercaptopyruvate (3MP), is regulated by Ca2+. H2S is oxidized to thiosulfate in mitochondria through the sequential action of sulfide quinone oxidoreductase (SQR), sulfur dioxygenase, and rhodanese. The rates of the production and clearance of H2S determine its cellular concentration. Polysulfides (H2Sn) have been found to occur in the brain and activate transient receptor potential ankyrin 1 (TRPA1) channels, facilitate the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus, and suppress the activity of phosphatase and tensin homolog (PTEN) by sulfurating (sulfhydrating) the target cysteine residues. A cross talk between H2S and NO also plays an important role in cardioprotection as well as regulation of the vascular tone. H2S, polysulfides, and their cross talk with NO may mediate various physiological and pathophysiological responses. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology
Molecules 2014, 19(8), 12789-12813; doi:10.3390/molecules190812789
Received: 8 July 2014 / Revised: 11 August 2014 / Accepted: 12 August 2014 / Published: 21 August 2014
Cited by 19 | PDF Full-text (1566 KB) | HTML Full-text | XML Full-text
Abstract
The understanding of sulfur bonding is undergoing change. Old theories on hypervalency of sulfur and the nature of the chalcogen-chalcogen bond are now questioned. At the same time, there is a rapidly expanding literature on the effects of sulfur in regulating biological [...] Read more.
The understanding of sulfur bonding is undergoing change. Old theories on hypervalency of sulfur and the nature of the chalcogen-chalcogen bond are now questioned. At the same time, there is a rapidly expanding literature on the effects of sulfur in regulating biological systems. The two fields are inter-related because the new understanding of the thiosulfoxide bond helps to explain the newfound roles of sulfur in biology. This review examines the nature of thiosulfoxide (sulfane, S0) sulfur, the history of its regulatory role, its generation in biological systems, and its functions in cells. The functions include synthesis of cofactors (molybdenum cofactor, iron-sulfur clusters), sulfuration of tRNA, modulation of enzyme activities, and regulating the redox environment by several mechanisms (including the enhancement of the reductive capacity of glutathione). A brief review of the analogous form of selenium suggests that the toxicity of selenium may be due to over-reduction caused by the powerful reductive activity of glutathione perselenide. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
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Open AccessReview Sulfur Amino Acids in Diet-induced Fatty Liver: A New Perspective Based on Recent Findings
Molecules 2014, 19(6), 8334-8349; doi:10.3390/molecules19068334
Received: 12 May 2014 / Revised: 6 June 2014 / Accepted: 9 June 2014 / Published: 19 June 2014
Cited by 3 | PDF Full-text (627 KB) | HTML Full-text | XML Full-text
Abstract
The relationship of sulfur amino acids to diet-induced fatty liver was established 80 years ago, with cystine promoting the condition and methionine preventing it. This relationship has renewed importance today because diet-induced fatty liver is relevant to the current epidemics of obesity, [...] Read more.
The relationship of sulfur amino acids to diet-induced fatty liver was established 80 years ago, with cystine promoting the condition and methionine preventing it. This relationship has renewed importance today because diet-induced fatty liver is relevant to the current epidemics of obesity, non-alcoholic fatty liver disease, metabolic syndrome, and type 2 diabetes. Two recent papers provide the first evidence linking sulfane sulfur to diet-induced fatty liver opening a new perspective on the problem. This review summarizes the early data on sulfur amino acids in fatty liver and correlates that data with current knowledge of sulfur metabolism. Evidence is reviewed showing that the lipotropic effect of methionine may be mediated by sulfane sulfur and that the hepatosteatogenic effect of cystine may be related to the removal of sulfane sulfur by cysteine catabolites. Possible preventive and therapeutic strategies are discussed. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
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