Control of protein function through oxidation and reduction of persulfidated states

Dóka, Éva; Ida, Tomoaki; Dagnell, Markus; Abiko, Yoshihiro; Luong, Nho Cong; Balog, Noémi; Takata, Tsuyoshi; Espinosa, Belén; Nishimura, Akira; Cheng, Qing; Funato, Yosuke; Miki, Hiroaki; Fukuto, Jon M.; Prigge, Justin R.; Schmidt, Edward E.; Arnér, Elias S.J.; Kumagai, Yoshito; Akaike, Takaaki; Nagy, Péter

doi:10.1126/sciadv.aax8358

Cited by 154 publications

(147 citation statements)

References 61 publications

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“…In contrast, the oxidation of per-sulfurated cysteine-SSO 2 H and -SSO 3 H can be converted to cysteine-SH by the reduced form of thioredoxin (Nagahara et al, 2012). These observations were reproduced and confirmed by other groups (Dóka et al, 2020;Zivanovic et al, 2019).…”

Section: Neuroprotective Rolesupporting

confidence: 58%

Hydrogen sulfide signalling in the CNS ‐ Comparison with NO

Kimura

2020

British J Pharmacology

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Hydrogen sulfide (H 2 S) together with polysulfides (H 2 S n , n > 2) are signalling molecules like NO with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation and oxygen sensing. H 2 S and H 2 S n diffuse to the target proteins for S-sulfurating their cysteine residues that induces the conformational changes to alter the activity. On the other hand, 3-mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3-mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S-nitrosylation. S-sulfuration and S-nitrosylation by enzymes proceed only inside the cell, while reactions induced by H 2 S, H 2 S n and NO even extend to the surrounding cells. Disturbance of signalling by these molecules as well as S-sulfuration and S-nitrosylation causes many nervous system diseases. This review focuses on the signalling by H 2 S and H 2 S n with S-sulfuration comparing to that of NO with S-nitrosylation and discusses on their roles in physiology and pathophysiology.

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Section: Neuroprotective Rolesupporting

confidence: 58%

Hydrogen sulfide signalling in the CNS ‐ Comparison with NO

Kimura

2020

British J Pharmacology

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“…Reactions with thiolates constitute one of the main decay pathways for persulfides in vivo (16,43,44). To our knowledge, the value of k-1,pH (1.11 M -1 s -1 ) is the first report for the rate constant of a reaction between a low molecular weight (LMW) persulfide and a LMW thiolate at physiological pH.…”

Section: Gssh + Gssgmentioning

confidence: 98%

“…RSSO2H and RSSO3H) that can be reduced by cellular reductants systems, while analogous oxidation of thiols yields irreversible oxidation products (i.e. RSO2H and RSO3H) (4,16,24,44).…”

Section: Biological Implicationsmentioning

confidence: 99%

“…Rhodanese can catalyze the reversible reaction between GSSH and sulfite to form GSH and thiosulfate (10,12,15). These processes suggest that GSSH plays key roles in vivo; indeed, concentrations of ~35 pmol/mg protein (~7 µM) in mouse liver tissue have been recently reported (16). Despite the growing interest in persulfides, their chemical characteristics are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Acidity and nucleophilic reactivity of glutathione persulfide

Benchoam

Semelak

Cuevasanta

et al. 2020

Journal of Biological Chemistry

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Persulfides (RSSH/RSS-) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of H2S. Despite their growing relevance, their chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/GSS-), the derivative of the abundant cellular thiol, glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and H2S. A pKa of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically-relevant electrophiles peroxynitrite and hydrogen peroxide, as well as with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through SN2 mechanisms. At neutral pH, GSSH reacted faster than GSH due to increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS- presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called alpha effect, i.e. the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the alpha effect correlated with the Brønsted nucleophilic factor, βnuc, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the pKa of a biological persulfide and the first examination of the alpha effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.

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“…Signaling roles of thiol persulfidation have recently begun to emerge. In addition, recent research points to an important role of persulfidation in protecting proteins from irreversible oxidation [27,28]. The target specificity of the various thiol modifications is an important aspect of redox signaling.…”

Section: Reactive Oxygen and Nitrogen Species Antioxidants And Thiomentioning

confidence: 99%

Oxidants, Antioxidants and Thiol Redox Switches in the Control of Regulated Cell Death Pathways

Benhar

2020

Antioxidants

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It is well appreciated that biological reactive oxygen and nitrogen species such as hydrogen peroxide, superoxide and nitric oxide, as well as endogenous antioxidant systems, are important modulators of cell survival and death in diverse organisms and cell types. In addition, oxidative stress, nitrosative stress and dysregulated cell death are implicated in a wide variety of pathological conditions, including cancer, cardiovascular and neurological diseases. Therefore, much effort is devoted to elucidate the molecular mechanisms linking oxidant/antioxidant systems and cell death pathways. This review is focused on thiol redox modifications as a major mechanism by which oxidants and antioxidants influence specific regulated cell death pathways in mammalian cells. Growing evidence indicates that redox modifications of cysteine residues in proteins are involved in the regulation of multiple cell death modalities, including apoptosis, necroptosis and pyroptosis. In addition, recent research suggests that thiol redox switches play a role in the crosstalk between apoptotic and necrotic forms of regulated cell death. Thus, thiol-based redox circuits provide an additional layer of control that determines when and how cells die.

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Control of protein function through oxidation and reduction of persulfidated states

Cited by 154 publications

References 61 publications

Hydrogen sulfide signalling in the CNS ‐ Comparison with NO

Hydrogen sulfide signalling in the CNS ‐ Comparison with NO

Acidity and nucleophilic reactivity of glutathione persulfide

Oxidants, Antioxidants and Thiol Redox Switches in the Control of Regulated Cell Death Pathways

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