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Special Issue "Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016"

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

Deadline for manuscript submissions: closed (31 October 2016)

Special Issue Editors

Guest Editor
Dr. Noriyuki Nagahara

Isotope Research Center, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
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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

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

Dear Colleagues,

During the rise of the oxygen concentration in the Earth’s atmosphere, sulfur atoms are 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.

Two years after the publication of the first Special Issue in 2014, a large number of investigations indicated large regulatory capacities of the endogenous pool of sulfide. Nowadays, the research in this area has focused on a variety of donor molecules used to investigate physiological action of sulfide in vitro.

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

Manuscript Submission Information

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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
  • polysulfides

Related Special Issue

Published Papers (23 papers)

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Editorial

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Open AccessFeature PaperEditorial Atomic Sulfur: An Element for Adaptation to an Oxidative Environment
Molecules 2017, 22(11), 1821; doi:10.3390/molecules22111821
Received: 23 October 2017 / Accepted: 24 October 2017 / Published: 26 October 2017
PDF Full-text (743 KB) | HTML Full-text | XML Full-text
Abstract
During the period of rising oxygen concentration in the Earth’s atmosphere (Figure 1), sulfur atoms were incorporated into proteins as redox-active cysteine residues [1] and antioxidant molecules such as thioredoxin, glutathione, and glutaredoxin appeared [...]
Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Research

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Open AccessArticle Hydrogen Sulphide Production in Healthy and Ulcerated Gastric Mucosa of Rats
Molecules 2017, 22(4), 530; doi:10.3390/molecules22040530
Received: 27 January 2017 / Revised: 13 March 2017 / Accepted: 22 March 2017 / Published: 27 March 2017
Cited by 2 | PDF Full-text (2190 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogen sulphide (H2S) is produced endogenously via two enzymes dependent on pyridoxal phosphate (PLP): cystathionine beta-synthase (CBS, EC 4.2.1.22), cystathionase γ-liase (CTH, EC 4.4.1.1), and a third, 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2). H2S strengthens the defence mechanisms of the
[...] Read more.
Hydrogen sulphide (H2S) is produced endogenously via two enzymes dependent on pyridoxal phosphate (PLP): cystathionine beta-synthase (CBS, EC 4.2.1.22), cystathionase γ-liase (CTH, EC 4.4.1.1), and a third, 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2). H2S strengthens the defence mechanisms of the gastric mucosal barrier, and plays an important role in gastroprotection, including the increased resistance to damage caused by various irritants and non-steroidal anti-inflammatory drugs. The study was conducted to determine the role of H2S in ulcerated gastric mucosa of rats caused by immobilization in cold water (WRS). The activity and expression of γ-cystathionase, cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and rhodanese was compared with healthy mucosa, together with H2S generation, and cysteine, glutathione, and cystathionine levels. The results showed that the defence mechanism against stress is associated with stimulation of the production of H2S in the tissue and confirmed the observed advantageous effect of H2S on healing of gastric ulcers. In case of animals pretreated with exogenous sources of H2S and NaHS, and some changes observed in the ulcerated gastric mucosa tend to return to values found in the healthy tissue, a finding that is in accordance with the previously determined gastroprotective properties of H2S. The results presented in this paper point to the possible role of rhodanese in H2S production in the gastric mucosa of rats, together with the earlier mentioned three enzymes, which are all active in this tissue. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Open AccessArticle Lipoic Acid as a Possible Pharmacological Source of Hydrogen Sulfide/Sulfane Sulfur
Molecules 2017, 22(3), 388; doi:10.3390/molecules22030388
Received: 16 January 2017 / Revised: 24 February 2017 / Accepted: 27 February 2017 / Published: 2 March 2017
Cited by 2 | PDF Full-text (1808 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to verify whether lipoic acid (LA) itself is a source of H2S and sulfane sulfur. It was investigated in vitro non-enzymatically and enzymatically (in the presence of rat tissue homogenate). The results indicate that
[...] Read more.
The aim of the present study was to verify whether lipoic acid (LA) itself is a source of H2S and sulfane sulfur. It was investigated in vitro non-enzymatically and enzymatically (in the presence of rat tissue homogenate). The results indicate that both H2S and sulfane sulfur are formed from LA non-enzymatically in the presence of environmental light. These results suggest that H2S is the first product of non-enzymatic light-dependent decomposition of LA that is, probably, next oxidized to sulfane sulfur-containing compound(s). The study performed in the presence of rat liver and kidney homogenate revealed an increase of H2S level in samples containing LA and its reduced form dihydrolipoic acid (DHLA). It was accompanied by a decrease in sulfane sulfur level. It seems that, in these conditions, DHLA acts as a reducing agent that releases H2S from an endogenous pool of sulfane sulfur compounds present in tissues. Simultaneously, it means that exogenous LA cannot be a direct donor of H2S/sulfane sulfur in animal tissues. The present study is an initial approach to the question whether LA itself is a donor of H2S/sulfane sulfur. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Open AccessArticle Exogenous and Endogenous Hydrogen Sulfide Protects Gastric Mucosa against the Formation and Time-Dependent Development of Ischemia/Reperfusion-Induced Acute Lesions Progressing into Deeper Ulcerations
Molecules 2017, 22(2), 295; doi:10.3390/molecules22020295
Received: 7 December 2016 / Revised: 6 February 2017 / Accepted: 11 February 2017 / Published: 15 February 2017
Cited by 6 | PDF Full-text (5860 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogen sulfide (H2S) is an endogenous mediator, synthesized from l-cysteine by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3-MST). The mechanism(s) involved in H2S-gastroprotection against ischemia/reperfusion (I/R) lesions and their time-dependent progression into deeper gastric ulcerations
[...] Read more.
Hydrogen sulfide (H2S) is an endogenous mediator, synthesized from l-cysteine by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3-MST). The mechanism(s) involved in H2S-gastroprotection against ischemia/reperfusion (I/R) lesions and their time-dependent progression into deeper gastric ulcerations have been little studied. We determined the effect of l-cysteine, H2S-releasing NaHS or slow H2S releasing compound GYY4137 on gastric blood flow (GBF) and gastric lesions induced by 30 min of I followed by 3, 6, 24 and 48 h of R. Role of endogenous prostaglandins (PGs), afferent sensory nerves releasing calcitonin gene-related peptide (CGRP), the gastric expression of hypoxia inducible factor (HIF)-1α and anti-oxidative enzymes were examined. Rats with or without capsaicin deactivation of sensory nerves were pretreated i.g. with vehicle, NaHS (18–180 μmol/kg) GYY4137 (90 μmol/kg) or l-cysteine (0.8–80 μmol/kg) alone or in combination with (1) indomethacin (14 μmol/kg i.p.), SC-560 (14 μmol/kg), celecoxib (26 μmol/kg); (2) capsazepine (13 μmol/kg i.p.); and (3) CGRP (2.5 nmol/kg i.p.). The area of I/R-induced gastric lesions and GBF were measured by planimetry and H2-gas clearance, respectively. Expression of mRNA for CSE, CBS, 3-MST, HIF-1α, glutathione peroxidase (GPx)-1, superoxide dismutase (SOD)-2 and sulfide production in gastric mucosa compromised by I/R were determined by real-time PCR and methylene blue method, respectively. NaHS and l-cysteine dose-dependently attenuated I/R-induced lesions while increasing the GBF, similarly to GYY4137 (90 μmol/kg). Capsaicin denervation and capsazepine but not COX-1 and COX-2 inhibitors reduced NaHS- and l-cysteine-induced protection and hyperemia. NaHS increased mRNA expression for SOD-2 and GPx-1 but not that for HIF-1α. NaHS which increased gastric mucosal sulfide release, prevented further progression of acute I/R injury into deeper gastric ulcers at 6, 24 and 48 h of R. We conclude that H2S-induced gastroprotection against I/R-injury is due to increase in gastric microcirculation, anti-oxidative properties and afferent sensory nerves activity but independent on endogenous prostaglandins. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Open AccessFeature PaperArticle Expression of 3-Mercaptopyruvate Sulfurtransferase in the Mouse
Molecules 2016, 21(12), 1707; doi:10.3390/molecules21121707
Received: 15 November 2016 / Revised: 6 December 2016 / Accepted: 7 December 2016 / Published: 11 December 2016
Cited by 1 | PDF Full-text (3039 KB) | HTML Full-text | XML Full-text
Abstract
3-Mercaptopyruvate sulfurtransferase (MST) is one of the principal enzymes for the production of hydrogen sulfide and polysulfides in mammalians, and emerging evidence supports the physiological significance of MST. As a fundamental study of the physiology and pathobiology of MST, it is necessary to
[...] Read more.
3-Mercaptopyruvate sulfurtransferase (MST) is one of the principal enzymes for the production of hydrogen sulfide and polysulfides in mammalians, and emerging evidence supports the physiological significance of MST. As a fundamental study of the physiology and pathobiology of MST, it is necessary to establish the tissue distribution of MST in mice. In the present study, the expression of MST in various organs of adult and fetal mice was analyzed by Western blotting and enzyme-immunohistochemistry. Moreover, the histology of MST gene–deficient mice was examined. Western blotting revealed that all organs examined had MST. The brain, liver, kidneys testes, and endocrine organs contained large amounts of MST, but the lungs, spleen, thymus, and small intestine did not. Immunohistochemically, the MST expression pattern varies in a cell-specific manner. In the brain, neural and glial cells are positively stained; in the lung, bronchiolar cells are preferentially stained; in the liver, hepatocytes around central veins are more strongly stained; renal convoluted cells are strongly stained; and pancreatic islets are strongly stained. Fetal tissues were studied, and MST expression was found to be similar before and after birth. Histological observation revealed no remarkable findings in MST gene–deficient mice. The present study revealed fundamental information regarding the MST expression of various organs in adult and fetal mice, and the morphological phenotype of MST gene–deficient mice. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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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 16 | 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 the
[...] 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
Cited by 3 | 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, as
[...] 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
Cited by 2 | 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 dimeric
[...] 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

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Open AccessReview The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites
Molecules 2017, 22(2), 259; doi:10.3390/molecules22020259
Received: 31 October 2016 / Accepted: 3 February 2017 / Published: 10 February 2017
Cited by 1 | PDF Full-text (4416 KB) | HTML Full-text | XML Full-text
Abstract
The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To
[...] Read more.
The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To contend with such harmful compounds, living organisms have evolved antioxidant strategies. In this sense, the thiol-dependent antioxidant defense systems play a central role. In all cases, cysteine constitutes the major building block on which such systems are constructed, being present in redox substrates such as glutathione, thioredoxin, and trypanothione, as well as at the catalytic site of a variety of reductases and peroxidases. In some cases, the related selenocysteine was incorporated at selected proteins. In invertebrate parasites, antioxidant systems have evolved in a diversity of both substrates and enzymes, representing a potential area in the design of anti-parasite strategies. The present review focus on the organization of the thiol-based antioxidant systems in invertebrate parasites. Differences between these taxa and its final mammal host is stressed. An understanding of the antioxidant defense mechanisms in this kind of parasites, as well as their interactions with the specific host is crucial in the design of drugs targeting these organisms. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
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Open AccessReview Hydrogen Sulfide in the Adipose Tissue—Physiology, Pathology and a Target for Pharmacotherapy
Molecules 2017, 22(1), 63; doi:10.3390/molecules22010063
Received: 8 November 2016 / Revised: 21 December 2016 / Accepted: 29 December 2016 / Published: 31 December 2016
Cited by 5 | PDF Full-text (246 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogen sulfide (H2S) is synthesized in the adipose tissue mainly by cystathionine γ-lyase (CSE). Several studies have demonstrated that H2S is involved in adipogenesis, that is the differentiation of preadipocytes to adipocytes, most likely by inhibiting phosphodiesterases and increasing
[...] Read more.
Hydrogen sulfide (H2S) is synthesized in the adipose tissue mainly by cystathionine γ-lyase (CSE). Several studies have demonstrated that H2S is involved in adipogenesis, that is the differentiation of preadipocytes to adipocytes, most likely by inhibiting phosphodiesterases and increasing cyclic AMP concentration. The effect of H2S on adipose tissue insulin sensitivity and glucose uptake is controversial. Some studies suggest that H2S inhibits insulin-induced glucose uptake and that excess of H2S contributes to adipose tissue insulin resistance in metabolic syndrome. In contrast, other studies have demonstrated that H2S stimulates glucose uptake and its deficiency contributes to insulin resistance. Similarly, the effect of H2S on adipose tissue lipolysis is controversial. H2S produced by perivascular adipose tissue decreases vascular tone by activating ATP-sensitive and/or voltage-gated potassium channels in smooth muscle cells. Experimental obesity induced by high calorie diet has a time dependent effect on H2S in perivascular adipose tissue; short and long-term obesity increase and decrease H2S production, respectively. Hyperglycemia has been consistently demonstrated to suppress CSE-H2S pathway in various adipose tissue depots. Finally, H2S deficiency may contribute to adipose tissue inflammation associated with obesity/metabolic syndrome. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
Open AccessReview Sulfur Atom in its Bound State Is a Unique Element Involved in Physiological Functions in Mammals
Molecules 2016, 21(12), 1753; doi:10.3390/molecules21121753
Received: 18 October 2016 / Revised: 12 December 2016 / Accepted: 15 December 2016 / Published: 21 December 2016
Cited by 7 | PDF Full-text (1618 KB) | HTML Full-text | XML Full-text
Abstract
It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term “sulfane sulfur” sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article,
[...] Read more.
It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term “sulfane sulfur” sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article, sulfane sulfur is described as sulfur atoms that are covalently bound only with sulfur atoms, and as this explanation was somewhat difficult to comprehend, it was not generally accepted. Thus, in the early 1990s, we redefined these sulfur species as “bound sulfur”, which easily converts to hydrogen sulfide on reduction with a thiol reducing agent. In other words, bound sulfur refers to a sulfur atom that exists in a zero to divalent form (0 to −2). The first part of this review focuses on the fluorescent derivatization HPLC method—which we developed for measurement of bound sulfur—and explains the distribution of bound sulfur and the hydrogen sulfide-producing ability of various tissues, as clarified by this method. Next, we discuss diverse physiological functions and involvement of polysulfide, a typical type of bound sulfur, in the redox regulation system. Additionally, we also address its possible physiological role in the central nervous system, based on its action of scavenging reactive carbonyl compounds. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Open AccessReview Redox Signaling Regulated by Cysteine Persulfide and Protein Polysulfidation
Molecules 2016, 21(12), 1721; doi:10.3390/molecules21121721
Received: 16 November 2016 / Revised: 8 December 2016 / Accepted: 9 December 2016 / Published: 15 December 2016
Cited by 5 | PDF Full-text (2156 KB) | HTML Full-text | XML Full-text
Abstract
For decades, reactive persulfide species including cysteine persulfide (CysSSH) have been known to exist endogenously in organisms. However, the physiological significance of endogenous persulfides remains poorly understood. That cystathionine β-synthase and cystathionine γ-lyase produced CysSSH from cystine was recently demonstrated. An endogenous sulfur
[...] Read more.
For decades, reactive persulfide species including cysteine persulfide (CysSSH) have been known to exist endogenously in organisms. However, the physiological significance of endogenous persulfides remains poorly understood. That cystathionine β-synthase and cystathionine γ-lyase produced CysSSH from cystine was recently demonstrated. An endogenous sulfur transfer system involving CysSSH evidently generates glutathione persulfide (GSSH) that exists at concentrations greater than 100 μM in vivo. Because reactive persulfide species such as CysSSH and GSSH have higher nucleophilicity than parental cysteine (Cys) and glutathione do, these reactive species exhibit strong scavenging activities against oxidants, e.g., hydrogen peroxide, and electrophiles, which contributes to redox signaling regulation. Also, several papers indicated that various proteins and enzymes have Cys polysulfides including CysSSH at their specific Cys residues, which is called protein polysulfidation. Apart from the redox signaling regulatory mechanism, another plausible function of protein polysulfidation is providing protection for protein thiol residues against irreversible chemical modification caused by oxidants and electrophiles. Elucidation of the redox signaling regulatory mechanism of reactive persulfide species including small thiol molecules and thiol-containing proteins should lead to the development of new therapeutic strategies and drug discoveries for oxidative and electrophilic stress-related diseases. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Open AccessReview Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System Homeostasis
Molecules 2016, 21(11), 1558; doi:10.3390/molecules21111558
Received: 5 October 2016 / Revised: 31 October 2016 / Accepted: 14 November 2016 / Published: 17 November 2016
Cited by 10 | PDF Full-text (652 KB) | HTML Full-text | XML Full-text
Abstract
Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may
[...] Read more.
Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may cross the gut-blood barrier and target blood vessels, the heart and other organs involved in the regulation of the circulatory system. A number of studies have shown that hydrogen sulfide (H2S) is an important biological mediator in the circulatory system. Thus far, research has focused on the effects of H2S enzymatically produced by cardiovascular tissues. However, some recent evidence indicates that H2S released in the colon may also contribute to the control of arterial blood pressure. Incidentally, sulfate-reducing bacteria are ubiquitous in mammalian colon, and H2S is just one among a number of molecules produced by the gut flora. Other gut bacteria-derived compounds that may affect the circulatory system include methane, nitric oxide, carbon monoxide, trimethylamine or indole. In this paper, we review studies that imply a role of gut microbiota and their metabolites, such as H2S, in circulatory system homeostasis. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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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 14 | 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. However,
[...] 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 2 | 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 formation
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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
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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 and
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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 21 | 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 initially
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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 10 | 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 phosphorylation,
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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 49 | 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), and
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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 42 | 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 systems.
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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 6 | 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, non-alcoholic
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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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Open AccessComment The Hydrogen Sulfide-Vitamin B12-Folic Acid Axis: An Intriguing Issue in Chronic Kidney Disease. A Comment on Toohey JI: “Possible Involvement of Hydrosulfide in B12-Dependent Methyl Group Transfer”. Molecules 2017, 22, 582, pii: E582
Molecules 2017, 22(7), 1216; doi:10.3390/molecules22071216
Received: 28 June 2017 / Revised: 13 July 2017 / Accepted: 18 July 2017 / Published: 19 July 2017
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(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
Open AccessHypothesis Possible Involvement of Hydrosulfide in B12-Dependent Methyl Group Transfer
Molecules 2017, 22(4), 582; doi:10.3390/molecules22040582
Received: 6 February 2017 / Revised: 22 March 2017 / Accepted: 30 March 2017 / Published: 5 April 2017
Cited by 2 | PDF Full-text (4651 KB) | HTML Full-text | XML Full-text
Abstract
Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B12-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane
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Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B12-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane sulfur/hydrogen sulfide (S°/H2S), hydrosulfide derivatives of cobalamins, autoxidation of hydrosulfide radical, radical S-adenosylmethionine methyl transfer (RSMT), and methionine synthase (MS). Then, new reaction mechanisms for B12-dependent methyl group transfer are proposed; the mechanisms are facile and overcome difficulties that existed in previously-accepted mechanisms. Finally, the theory is applied to the effect of S°/H2S in nerve tissue involving the “hypomethylation theory” that was proposed 50 years ago to explain the neuropathology resulting from deficiency of vitamin B12 or folic acid. The conclusions are consistent with emerging evidence that sulfane sulfur/hydrogen sulfide may be beneficial in treating Alzheimer’s disease. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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