Reactive Sulfur Species Research Articles

Taming the Dichalcogenides: Isolation, Characterization, and Reactivity of Elusive Perselenide, Persulfide, Thioselenide, and Selenosulfide Anions.

Reactive sulfur species (RSS) and reactive selenium species (RSeS) play integral roles in hydrogen sulfide (H2S) and hydrogen selenide (H2Se) biological signaling pathways, and dichalcogenide anions are proposed transient intermediates that facilitate a variety of biochemical transformations. Herein we report the selective synthesis, isolation, spectroscopic and structural characterization, and fundamental reactivity of persulfide (RSS-), perselenide (RSeSe-), thioselenide (RSSe-), and selenosulfide (RSeS-) anions. The isolated chalcogenides do not rely on steric protection for stability and have steric profiles analogous to cysteine (Cys). Simple reduction of S8 or Se by potassium benzyl thiolate (KSBn) or selenolate (KSeBn) in the presence of 18-crown-6 afforded [K(18-crown-6)][BnSS] (1), [K(18-crown-6)][BnSeSe] (2), [K(18-crown-6][BnSSe] (3), and [K(18-crown-6][BnSeS] (4). The chemical structure of each dichalcogenide was confirmed by X-ray crystallography and solution-state 1H, 13C, and 77Se NMR spectroscopy. To advance our understanding of the reactivity of these species, we demonstrated that reduction of 1-4 by PPh3 readily generates E═PPh3 (E: S, Se), and reduction of 1, 3, and 4 by DTT readily produces HE-/H2E. Furthermore, 1-4 react with CN- to produce ECN-, which is consistent with the detoxifying effects of dichalcogenide intermediates in the Rhodanese enzyme. Taken together, this work provides new insights into the inherent structural and reactivity characteristics of dichalcogenides relevant to biology and advances our understanding of the fundamental properties of these reactive anions.

Sulfur-Containing Persistent Free Radicals and Reactive Species on Photoaged Microplastics: Identification and the Formation Mechanism.

The elemental composition may affect the persistent free radical (PFR) and reactive species (RS) formation associated with photoaging microplastics; however, a relevant study is still lacking. This study systematically investigated the formation, evolution, and types of PFRs and RS on sulfur-containing microplastics (S-MPs) under simulated sunlight. Electron paramagnetic resonance detection and power saturation curve analysis isolated three different PFRs on each photoaging poly(phenylene sulfide) (PPS) and polysulfone (PSF). Combining the results of characterization and density functional theory calculation, these observed PFRs on the irradiated S-MPs were classified as oxygen-centered radicals with an adjacent S atom (namely, thio-oxygen radicals), oxygen-centered and sulfur-centered radicals, where the thio-oxygen radicals on PPS were benzenethiol-like radicals, and oxygen-centered radicals and sulfur-centered radicals on PSF that were identified as benzenesulfonic-like radicals and phenyl sulfonyl-like radicals, respectively. Moreover, potential precursor molecule fragments of PFRs on the photoaging S-MPs, including p-toluenesulfinic acid and benzenesulfonic acid, were detected by pyrolysis-gas chromatography/mass spectrometry and liquid chromatography-mass spectrometry. Interestingly, reactive sulfur species (SO3•-) was also observed on irradiated S-MPs in addition to reactive oxygen species, which was mainly derived from the reaction of •OH and sulfonyl radicals. These results have implications for assessing the potential risks of atmospheric S-MPs.

Reactive Sulfur Species Omics Analysis in the Brain Tissue of the 5xFAD Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whereby oxidative stress augmentation results in mitochondrial dysfunction and cell death by apoptosis. Emerging evidence indicates that reactive sulfur species (RSS), such as glutathione hydropersulfide (GSSH), is endogenously produced, functions as potent antioxidants, and regulate redox signaling through the formation of protein polysulfides. However, the relationship between RSS and AD pathogenesis is not fully understood. In this study, we analyzed endogenous RSS production in the brain tissue of a familial AD model (5xFAD) mouse using multiple RSS-omics approaches. Memory impairment, increased amyloid plaques, and neuroinflammation have been confirmed in 5xFAD mice. Quantitative RSS omics analysis revealed that the total polysulfide content was significantly decreased in the brains of 5xFAD mice, whereas there was no significant difference in the levels of glutathione, GSSH, or hydrogen sulfide between wild-type and 5xFAD mice. In contrast, a significant decline in the protein polysulfide status was observed in the brains of 5xFAD mice, suggesting that RSS production and subsequent redox signaling might be altered during the onset and progression of AD. Our findings have important implications for understanding the significance of RSS in the development of preventive and therapeutic strategies for AD.

The emerging key role of reactive sulfur species in abiotic stress tolerance in plants.

In plants, sulfur plays a critical role in the formation of important biomolecules such as cysteine, methionine, and tripeptide glutathione. Thiol groups, composed of sulfur, are essential to numerous metabolic processes. The easy and reversible oxidation and reduction of thiol groups have drawn attention to the redox regulation of cellular metabolism. Reactive sulfur species (RSS), including hydrogen sulfide (H2 S), persulfides and polysulfides, are synthetized in all living organisms, mainly from cysteine, and have been recognized in the last two decades as very important molecules in redox regulation. RSS are considered potent signaling molecules, being involved in the regulation of virtually all aspects of cell function. With regard to stress, reactive species and the antioxidant machinery maintain a delicate balance that gets disturbed under stress conditions, wherein reactive species biosynthesis, transportation, scavenging, and overall metabolism become decisive for plant survival. While reactive oxygen and nitrogen species have been much discussed over recent years, research into reactive sulfur species (RSS) biosynthesis, signaling, and relation to abiotic stresses is still nascent. RSS evolved long before reactive oxygen species, and because both are metabolized by catalase, it has been suggested that "antioxidant" enzymes originally evolved to regulate RSS and may still do so today. In this review, we have tried to summarize the generation, signaling, and interaction of RSS in plant systems and to discuss in detail the roles under various abiotic stresses. This article is protected by copyright. All rights reserved.

Prediction of band edge potentials and reaction products in photocatalytic copper and iron sulfides.

The prediction of band edge potentials in photocatalytic materials is an important but challenging task. In contrast, bandgaps can be easily determined through absorption spectra. Here, we present two simple theoretical approaches for the determination of band edge potentials which are based on the electron negativity and work function of each constituent atom. We use these approaches to determine band edge potentials in semiconducting metallic oxides and sulfides, such as titanium dioxide (TiO2), chalcopyrite (CuFeS2), pyrite (FeS2), covellite (CuS), and chalcocite (Cu2S) with respect to an absolute scale (eV) and an electrochemical scale (V). Until now, there is little information on iron and copper sulfides referring to these thermodynamic parameters.TiO2 (Titania p25) was used as reference semiconductor to validate the calculation procedures using experimental values by X-ray diffraction analysis (XRD), diffuse reflectance spectrometry (DRS), and electron paramagnetic resonance spectroscopy (EPR). The production of key chemical species such as reactive oxygen species (ROS) and reactive sulfur species (RSS) has been theoretically and experimentally determined by EPR.

Redox and Nucleophilic Reactions of Naphthoquinones with Small Thiols and Their Effects on Oxidization of H2S to Inorganic and Organic Hydropolysulfides and Thiosulfate.

Naphthoquinone (1,4-NQ) and its derivatives (NQs, juglone, plumbagin, 2-methoxy-1,4-NQ, and menadione) have a variety of therapeutic applications, many of which are attributed to redox cycling and the production of reactive oxygen species (ROS). We previously demonstrated that NQs also oxidize hydrogen sulfide (H2S) to reactive sulfur species (RSS), potentially conveying identical benefits. Here we use RSS-specific fluorophores, mass spectroscopy, EPR and UV-Vis spectrometry, and oxygen-sensitive optodes to examine the effects of thiols and thiol-NQ adducts on H2S-NQ reactions. In the presence of glutathione (GSH) and cysteine (Cys), 1,4-NQ oxidizes H2S to both inorganic and organic hydroper-/hydropolysulfides (R2Sn, R=H, Cys, GSH; n = 2-4) and organic sulfoxides (GSnOH, n = 1, 2). These reactions reduce NQs and consume oxygen via a semiquinone intermediate. NQs are also reduced as they form adducts with GSH, Cys, protein thiols, and amines. Thiol, but not amine, adducts may increase or decrease H2S oxidation in reactions that are both NQ- and thiol-specific. Amine adducts also inhibit the formation of thiol adducts. These results suggest that NQs may react with endogenous thiols, including GSH, Cys, and protein Cys, and that these adducts may affect both thiol reactions as well as RSS production from H2S.

Reactive sulfur species disaggregate the SQSTM1/p62-based aggresome-like induced structures via the HSP70 induction and prevent parthanatos

Reactive sulfur species (RSS) have emerged as key regulators of protein quality control. However, the mechanisms by which RSS contribute to cellular processes are not fully understood. In this study, we identified a novel function of RSS in preventing parthanatos, a nonapoptotic form of cell death that is induced by poly (ADP-ribose) polymerase-1 and mediated by the aggresome-like induced structures (ALIS) composed of SQSTM1/p62. We found that sodium tetrasulfide (Na2S4), a donor of RSS, strongly suppressed oxidative stress-dependent ALIS formation and subsequent parthanatos. On the other hand, the inhibitors of the RSS-producing enzymes, such as 3-mercaptopyruvate sulfurtransferase and cystathionine γ-lyase, clearly enhanced ALIS formation and parthanatos. Interestingly, we found that Na2S4 activated heat shock factor 1 by promoting its dissociation from heat shock protein 90, leading to accelerated transcription of HSP70. Considering that the genetic deletion of HSP70 allowed the enhanced ALIS formation, these findings suggest that RSS prevent parthanatos by specifically suppressing ALIS formation through induction of HSP70. Taken together, our results demonstrate a novel mechanism by which RSS prevent cell death, as well as a novel physiological role of RSS in contributing to protein quality control through HSP70 induction, which may lead to better understanding of the bioactivity of RSS.

Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism.

Reactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bound thiols. The chemical properties and great supply of these molecular species suggest a pivotal role for reactive persulfides/polysulfides in different cellular regulatory processes (e.g., energy metabolism and redox signaling). We demonstrated earlier that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase (CPERS) and is responsible for the in vivo production of most reactive persulfides (polysulfides). Some researchers continue to suggest that 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) may also produce hydrogen sulfide and persulfides that may be generated during the transfer of sulfur from 3-mercaptopyruvate to the cysteine residues of 3-MST or direct synthesis from cysteine by CBS/CSE, respectively. We thus used integrated sulfur metabolome analysis, which we recently developed, with 3-MST knockout (KO) mice and CBS/CSE/3-MST triple-KO mice, to elucidate the possible contribution of 3-MST, CBS, and CSE to the production of reactive persulfides in vivo. We therefore quantified various sulfide metabolites in organs derived from these mutant mice and their wild-type littermates via this sulfur metabolome, which clearly revealed no significant difference between mutant mice and wild-type mice in terms of reactive persulfide production. This result indicates that 3-MST, CBS, and CSE are not major sources of endogenous reactive persulfide production; rather, CARS/CPERS is the principal enzyme that is actually involved in and even primarily responsible for the biosynthesis of reactive persulfides and polysulfides in vivo in mammals.

Free radicals and antioxidant system

Free radicals are compounds characterized by having an unpaired electron in their outer orbit, a condition that makes them highly reactive, i.e., they interact through diffusion-controlled reactions with proteins, lipids and nucleic acids.They have also been referred to as reactive oxygen species (ROS), reactive nitrogen species (RNS) or reactive sulfur species(RSS). In the human organism, they are mainly produced in the mitochondrial electron transport chain, where respiratorycomplexes I and III specifically participate and reduce oxygen by converting it into superoxide anion. Likewise, they canbe formed through a wide variety of enzymatic and non-enzymatic reactions involving substances that are synthesized by cells or are ingested with food and some medicines. Human beings have an antioxidant system which is both enzymaticand non-enzymatic in nature and whose function is to protect the organism from the harmful action of free radicals. Thissystem includes enzymes—such as catalase, superoxide dismutase, thioredoxin, etc.—and non-enzymatic compounds—such as glutathione, ferritin, myoglobin, etc. However, they are not efficient enough to protect it, so it is necessary to eat foods that contain substances with antioxidant properties whose protective action will depend on their chemical reactivity and their concentration. These antioxidant compounds are mainly found in fruits and vegetables, where polyphenols, flavonoids, carotenoids, vitamin C, vitamin E, etc. have been identified. A significant amount of evidence suggests that the intake of antioxidant substances protects the body from the damaging effect of free radicals, but when the oxidative action prevails over the antioxidant action, it can lead to oxidative stress, a condition that is closely linked to a wide variety of chronic non-communicable diseases including cancer, diabetes mellitus, obesity, psoriasis, atherosclerosis,among others. All this seems to indicate that the term “cellular redox steady state” more appropriately describes the constant adaptation to a situation of rapid chemical turnover and suggests that the substances involved in this process be designated as “biologically reactive species” due to the existence of harmful compounds such as hydrogen peroxide, peroxynitrite, etc., which are not—strictly speaking—free radicals but have toxic effects on cells.

Recent Advances in Biotechnologies for the Treatment of Environmental Pollutants Based on Reactive Sulfur Species

The definition of reactive sulfur species (RSS) is inspired by the reactivity and variable chemical valence of sulfur. Sulfur is an essential element for life and is a part of global geochemical cycles. Wastewater treatment bioreactors can be divided into two major categories: sulfur reduction and sulfur oxidation. We review the origins of the definition of RSS and related biotechnological processes in environmental management. Sulfate reduction, sulfide oxidation, and sulfur-based redox reactions are key to driving the coupled global carbon, nitrogen, and sulfur co-cycles. This shows the coupling of the sulfur cycle with the carbon and nitrogen cycles and provides insights into the global material-chemical cycle. We also review the biological classification and RSS metabolic mechanisms of functional microorganisms involved in the biological processes, such as sulfate-reducing and sulfur-oxidizing bacteria. Developments in molecular biology and genomic technologies have allowed us to obtain detailed information on these bacteria. The importance of RSS in environmental technologies requires further consideration.

Investigating the debrominations of a subset of brominated flame retardants by biogenic reactive sulfur species

Brominated flame retardants (BFRs) are persistent organic pollutants. Many bacteria are able to debrominate BFRs, but the underlying mechanism is unclear. Herein, we discovered that reactive sulfur species (RSS), which have strong reductive activity and are commonly present in bacteria, might be one of the reasons leading to such ability. Experiments performed with RSS (H2S and HSSH) and BFRs indicated that RSS can debrominate BFRs via two different mechanisms simultaneously: the substitutive debromination that generates thiol-BFRs and the reductive debromination that generates hydrogenated BFRs. Debromination reactions rapidly happened under neutral pH and ambient temperature, and the debromination degree was around 30% − 55% in one hour. Two Pseudomonas strains, Pseudomonas sp. C27 and Pseudomonas putida B6-2 both produced extracellular RSS and showed debromination activity. C27 debrominated HBCD, TBECH, and TBP by 5.4%, 17.7%, and 15.9% in two days. Whereas, B6-2 debrominated the three BFRs by 0.4%, 0.6%, and 0.3% in two days. The two bacteria produced different amounts and species of RSS, which were likely responsible for the contrasted degrees of the debromination. Our finding unveiled a novel, non-enzymatic debromination mechanism that many bacteria may possess. RSS producing bacteria have potentials to contribute to bioremediation of BFRs-polluted environments.

Advances of H2S in Regulating Neurodegenerative Diseases by Preserving Mitochondria Function

Neurotoxicity is induced by different toxic substances, including environmental chemicals, drugs, and pathogenic toxins, resulting in oxidative damage and neurodegeneration in mammals. The nervous system is extremely vulnerable to oxidative stress because of its high oxygen demand. Mitochondria are the main source of ATP production in the brain neuron, and oxidative stress-caused mitochondrial dysfunction is implicated in neurodegenerative diseases. H2S was initially identified as a toxic gas; however, more recently, it has been recognized as a neuromodulator as well as a neuroprotectant. Specifically, it modulates mitochondrial activity, and H2S oxidation in mitochondria produces various reactive sulfur species, thus modifying proteins through sulfhydration. This review focused on highlighting the neuron modulation role of H2S in regulating neurodegenerative diseases through anti-oxidative, anti-inflammatory, anti-apoptotic and S-sulfhydration, and emphasized the importance of H2S as a therapeutic molecule for neurological diseases.

Bioresponsive fluorescent probes active in the second near‐infrared window

AbstractEmerging stimuli‐responsive composite probes active in the second near‐infrared window (NIR‐II, 1000–1700 nm) hold vast potential for improving in vivo imaging performance with minimized noise interference. The interactions among external irradiation, shell species, and the emissive core are key factors in the design of smart structures. The external irradiation provides energy for shell species and the emissive core to generate intense NIR‐II fluorescence signals, while the energy transfer process hinders NIR‐II emission in the inner structure of smart composite probes. However, if pathophysiological stimuli interrupt the above processes, then NIR‐II fluorescence signals are recovered. This review covers NIR‐II imaging based on diverse smart composite NIR‐II fluorescent probes responding to various biological stimuli, including ONOO−, overexpressed reactive sulfur species, abnormally expressed enzymes, and abnormal levels of physiological metabolites. Finally, to appreciate these advances, the challenges and perspectives of stimuli‐responsive composite NIR‐II probes are highlighted.

Organelle-Targeted Fluorescent Probes for Sulfane Sulfur Species.

Sulfane sulfurs, which include hydropersulfides (RSSH), hydrogen polysulfides (H2Sn, n > 1), and polysulfides (RSnR, n > 2), play important roles in cellular redox biology and are closely linked to hydrogen sulfide (H2S) signaling. While most studies on sulfane sulfur detection have focused on sulfane sulfurs in the whole cell, increasing the recognition of the effects of reactive sulfur species on the functions of various subcellular organelles has emerged. This has driven a need for organelle-targeted detection methods. However, the detection of sulfane sulfurs, particularly of RSSH and H2Sn, in biological systems is still a challenge due to their low endogenous concentrations and instabilities. In this review, we summarize the development and design of organelle-targeted fluorescent sulfane sulfur probes, examine their organelle-targeting strategies and choices of fluorophores (e.g., ratiometric, near-infrared, etc.), and discuss their mechanisms and ability to detect endogenous and exogenous sulfane sulfur species. We also present the advantages and limitations of the probes and propose directions for future work on this topic.

Exploration the homeostasis of signaling molecules in monocotyledonous crops with different CuO nanoparticle tolerance

Copper is an essential microelement that is indispensable for plant growth and development. The use of copper oxide nanoparticles (CuO NPs) in industry and agriculture has also increased because of their beneficial properties. However, excess amounts of CuO NPs may negatively affect the growth of monocotyledonous plant species, primarily through the generation of reactive oxygen species, which results in oxidative stress. Despite their increasingly widespread use, little is known regarding the signaling processes responsible for the effects of CuO NPs on the growth of monocotyledonous crops, or their impact on the homeostasis of reactive nitrogen species, hydrogen sulfide, and protein tyrosine nitration.In this study, the concentration of CuO NP that inhibits 50% of root growth was determined using sorghum, wheat, rye, and triticale as model plant species, and the NP-induced stress response and the balance of reactive molecules were assessed. Based on the effective concentration of CuO NP, wheat, rye, and triticale were more tolerant compared with sorghum, and entirely different response mechanisms in the homeostasis of reactive oxygen, nitrogen and sulfur species were observed. For the sensitive sorghum roots, the amount of reactive molecules was not significantly altered, whereas a significant increase in protein tyrosine nitration indicated a severely stressful state caused by CuO NPs. In contrast, the amount of reactive molecules increased significantly in the roots of the relatively tolerant species, and while the appearance of lipid peroxidation indicated oxidative stress, different changes in protein tyrosine nitration was associated with tolerance. The significant CuO NP-induced rise of endogenous H2S content in the root tips may be partly responsible for the relative tolerance of wheat, rye, and triticale compared with sorghum. CuO NP stress induced distinct modifications in the root tip cell walls of the examined species, where lignification was observed in the relatively sensitive sorghum, while in the tolerant species only callose deposition was detected. Overall, our results demonstrate that while monocotyledonous species with different CuO NP sensitivities may exhibit similar growth responses, the underlying changes in the dynamics of reactive molecules influence their tolerance.

Two-photon ratiometric imaging of endogenous reactive inorganic sulfur species in the cellular cushion toward formaldehyde

To address the potential biological relationship between reactive inorganic sulfur species (RISSs) and formaldehyde, the novel two-photon ratiometric RISSs probes (PH-RISSs) were synthesized practically with high selectivity and sensitivity toward RISSs and the related two-photon microscopic imaging assay was established which could be employed in the interpretation of the potential interaction between RISSs and formaldehyde. It was disclosed that the level of RISSs would raise toward formaldehyde and this behavior could be prohibited by CSE (cystathionine gamma lyase) inhibitor and reactive oxygen species (ROS) inhibitor, which indicated that formaldehyde could facilitate the metabolism of biothiols by CSE and this motivation of RISSs should be related with ROS intimately. Thus, RISSs might provide the critical biological compensation toward formaldehyde in a short term for living system and this two-photon ratiometric technique could be a practical tool to understand further the detailed interaction between aldehydes and RISSs in living systems.

Yohimbine Alleviates Oxidative Stress and Suppresses Aerobic Cysteine Metabolism Elevated in the Rat Liver of High-Fat Diet-Fed Rats.

Yohimbine is a small indole alkaloid derived from the bark of the yohimbe tree with documented biological activity, including anti-inflammatory, erectile dysfunction relieving, and fat-burning properties. Hydrogen sulfide (H2S) and sulfane sulfur-containing compounds are regarded as important molecules in redox regulation and are involved in many physiological processes. Recently, their role in the pathophysiology of obesity and obesity-induced liver injury was also reported. The aim of the present study was to verify whether the mechanism of biological activity of yohimbine is related to reactive sulfur species formed during cysteine catabolism. We tested the effect of yohimbine at doses of 2 and 5 mg/kg/day administered for 30 days on aerobic and anaerobic catabolism of cysteine and oxidative processes in the liver of high-fat diet (HFD)-induced obese rats. Our study revealed that HFD resulted in a decrease in cysteine and sulfane sulfur levels in the liver, while sulfates were elevated. In the liver of obese rats, rhodanese expression was diminished while lipid peroxidation increased. Yohimbine did not influence sulfane sulfur and thiol levels in the liver of obese rats, however, this alkaloid at a dose of 5 mg decreased sulfates to the control level and induced expression of rhodanese. Moreover, it diminished hepatic lipid peroxidation. It can be concluded that HFD attenuates anaerobic and enhances aerobic cysteine catabolism and induces lipid peroxidation in the rat liver. Yohimbine at a dose of 5 mg/kg can alleviate oxidative stress and reduce elevated concentrations of sulfate probably by the induction of TST expression.

The Transcriptional Repressor PerR Senses Sulfane Sulfur by Cysteine Persulfidation at the Structural Zn2+ Site in Synechococcus sp. PCC7002.

Cyanobacteria can perform both anoxygenic and oxygenic photosynthesis, a characteristic which ensured that these organisms were crucial in the evolution of the early Earth and the biosphere. Reactive oxygen species (ROS) produced in oxygenic photosynthesis and reactive sulfur species (RSS) produced in anoxygenic photosynthesis are closely related to intracellular redox equilibrium. ROS comprise superoxide anion (O2●-), hydrogen peroxide (H2O2), and hydroxyl radicals (●OH). RSS comprise H2S and sulfane sulfur (persulfide, polysulfide, and S8). Although the sensing mechanism for ROS in cyanobacteria has been explored, that of RSS has not been elucidated. Here, we studied the function of the transcriptional repressor PerR in RSS sensing in Synechococcus sp. PCC7002 (PCC7002). PerR was previously reported to sense ROS; however, our results revealed that it also participated in RSS sensing. PerR repressed the expression of prxI and downregulated the tolerance of PCC7002 to polysulfide (H2Sn). The reporter system indicated that PerR sensed H2Sn. Cys121 of the Cys4:Zn2+ site, which contains four cysteines (Cys121, Cys124, Cys160, and Cys163) bound to one zinc atom, could be modified by H2Sn to Cys121-SSH, as a result of which the zinc atom was released from the site. Moreover, Cys19 could also be modified by polysulfide to Cys19-SSH. Thus, our results reveal that PerR, a representative of the Cys4 zinc finger proteins, senses H2Sn. Our findings provide a new perspective to explore the adaptation strategy of cyanobacteria in Proterozoic and contemporary sulfurization oceans.

Affinity Studies of Hemicyanine Derived Water Soluble Colorimetric Probes with Reactive Oxygen/Nitrogen/Sulfur Species.

Peroxynitrite (ONOO- ) is an essential endogenous reactive oxygen species (ROS) generated in mitochondria under various pathological and physiological conditions. An increase in its level in mitochondria is related to numerous diseases. Herein, we report a series of hemicyanine-derived water-soluble colorimetric probes (1-4) and the reactivity of which was studied with various reactive oxygen, nitrogen, and sulfur species. Probes 1-4 are formed by conjugating 1,2,3,3-tetramethyl-3H-indolium iodide and 4-hydroxybenzaldehyde or its derivatives through an alkene linkage formed by the Knoevenagel reaction. Oxidative cleavage of the electron-rich double bond of the conjugated hemicyanine dye revealed a discerning affinity of probe 3 towards peroxynitrite among all reactive oxygen species. The rapid change in color of 3 provides a sensitive and selective method for detecting peroxynitrite with a low detection limit of 180 nM. Notably, the water solubility of the probe displays excellent performance for the selective detection of peroxynitrite among ROS and reactive nitrogen (RNS)/sulfur species (RSS). UV-vis, 1 H NMR, and 13 C NMR spectroscopic data and results from theoretical calculations provide further information on the interaction of peroxynitrite with probe 3.

Hydropersulfides (RSSH) attenuate doxorubicin-induced cardiotoxicity while boosting its anticancer action

Cardiotoxicity is a frequent and often lethal complication of doxorubicin (DOX)-based chemotherapy. Here, we report that hydropersulfides (RSSH) are the most effective reactive sulfur species in conferring protection against DOX-induced toxicity in H9c2 cardiac cells. Mechanistically, RSSH supplementation alleviates the DOX-evoked surge in reactive oxygen species (ROS), activating nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways, thus boosting endogenous antioxidant defenses. Simultaneously, RSSH turns on peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a master regulator of mitochondrial function, while decreasing caspase-3 activity to inhibit apoptosis. Of note, we find that RSSH potentiate anticancer DOX effects in three different cancer cell lines, with evidence that suggests this occurs via induction of reductive stress. Indeed, cancer cells already exhibit much higher basal hydrogen sulfide (H2S), sulfane sulfur, and reducing equivalents compared to cardiac cells. Thus, RSSH may represent a new promising avenue to fend off DOX-induced cardiotoxicity while boosting its anticancer effects.