Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases

Kruithof, Paul D; Lunev, Sergey; Lozano, Sheila P Aguilar; Batista, Fabiano Bianchini; Al-Dahmani, Zayana M; Joles, Jaap A.; Dolga, Amalia M.; Groves, Matthew R.; Goor, Harry van

doi:10.1016/j.bbadis.2020.165716

Cited by 51 publications

(67 citation statements)

References 87 publications

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“…STS has great potential due to both the H 2 S-related effects and the complementary effects of STS itself. Furthermore, additional anti-inflammatory and antioxidant effects of STS are related to its reaction with mitochondrial thiosulfate sulfurtransferase and its subsequent ROS scavenging effects [ 37 ]. In addition, pH-sensitive H 2 S donors have been developed including intramolecular cyclization-based donors (JK) and ammonium tetrathiomolybdate (ATTM) [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Donor Heart Preservation with Hydrogen Sulfide: A Systematic Review and Meta-Analysis

Ertugrul

Suylen

Damman

et al. 2021

IJMS

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Preclinical studies have shown that postconditioning with hydrogen sulfide (H2S) exerts cardioprotective effects against myocardial ischemia-reperfusion injury (IRI). The aim of this study was to appraise the current evidence of the cardioprotective effects of H2S against IRI in order to explore the future implementation of H2S in clinical cardiac transplantation. The current literature on H2S postconditioning in the setting of global myocardial ischemia was systematically reviewed and analyzed, performing meta-analyses. A literature search of the electronic databases Medline, Embase and Cinahl identified 1835 studies that were subjected to our pre-defined inclusion criteria. Sixteen studies were considered eligible for inclusion. Postconditioning with H2S showed significant robust effects with regard to limiting infarct size (standardized mean difference (SMD) = −4.12, 95% CI [−5.53–−2.71], p < 0.00001). Furthermore, H2S postconditioning consistently resulted in a significantly lower release of cardiac injury markers, lower levels of oxidative stress and improved cardiac function. Postconditioning with slow-releasing H2S donors offers a valuable opportunity for novel therapies within cardiac preservation for transplantation. Before clinical implication, studies evaluating the long-term effects of H2S treatment and effects of H2S treatment in large animal studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Donor Heart Preservation with Hydrogen Sulfide: A Systematic Review and Meta-Analysis

Ertugrul

Suylen

Damman

et al. 2021

IJMS

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“…Rhodanase is a mitochondrial enzyme that transfers a sulfur atom from sulfane-containing donor to the thiophilic acceptor substrate [ 31 ]. The catalytic activity of rhodanase occurs via a double displacement mechanism, where the active site, a cysteine residue (Cys247), accepts a sulfur atom from the persulfide intermediate state, followed by the transfer of sulfide sulfur from the enzyme to the nucleophilic acceptor sulfite, which produces thiosulfate ( Figure 1 ) [ 32 ]. Although human mitochondria also utilize this sulfide oxidation pathway, recent evidence suggests that glutathione (GSH) functions as a persulfide acceptor for human SQR to produce the persulfide intermediate [ 33 , 34 ].…”

Section: Hydrogen Sulfide As a Gasotransmittermentioning

confidence: 99%

Hydrogen Sulfide Metabolite, Sodium Thiosulfate: Clinical Applications and Underlying Molecular Mechanisms

Zhang

Dugbartey

Juriasingani

et al. 2021

IJMS

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Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (H2S), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from H2S, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.

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“…It was interesting to note that antioxidants seemed to undergo more regulatory changes than large absolute shifts in oxidation, which was evident by the number of antioxidant proteins identified utilizing the Ox(ratio) equation (Figure 2C, lower equation). Alongside PRDX5, a few components involved in glutathione activity have been identified including Thiosulfate:glutathione Sulfurtransferase (TSTD1), a reducing agent of both glutathione (GSH) and thioredoxin (TXN) (145). TSTD1 was found oxidized at Cys79 (+3%) that is its functional and sensitive thiol.…”

Section: Fine-tuning Mtros Along Metabolic Reprogramming Of T Cellsmentioning

confidence: 99%

Identification of mtROS-sensitive processes in activated CD4⁺T cells

Meston

Rietschel

et al. 2020

Preprint

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T lymphocytes are key components in adaptive immunity and their activation naturally involves mitochondrial-derived oxygen species (mtROS). In particular, H2O2 has been implicated as an important signaling molecule regulating major T cell functions. H2O2 targets the oxidation status of functional cysteine residues but knowledge if and where this happens in T cell signaling networks is widely missing. This study aimed to identify mtROS-sensitive processes in activated primary human CD4 + T cells. By using a thiolspecific redox proteomic approach we examined the oxidation state of 4784 cysteinecontaining peptides of ex vivo stimulated T cells from healthy individuals. Upon activation, a shift in oxidation was observed at catalytic cysteine residues of peroxiredoxins (PRDX5 & PRDX6), and T cells were found to maintain their global thiol-redox homeostasis. In parallel, a distinct set of 88 cysteine residues were found to be differentially oxidized upon T cell activation suggesting novel functional thiol switches. In mitochondria, cysteine oxidations selectively modified regulators of respiration (NDUFA2, NDUFA8, and UQCRH) confirming electron leakage from electron transport complexes I and III. The majority of oxidations occurred outside mitochondria and enriched sensitive thiols at regulators of cytoskeleton dynamics (e.g. CYFIP2 and ARPC1B) and known immune functions including the non-receptor tyrosine phosphatase PTPN7. Conversely, cysteine reduction occurred predominantly at transcriptional regulators and sites that coordinate zinc-binding in zinc-finger motifs. Indeed, fluorescence microscopy revealed a colocalization of zinc-rich microenvironments and mitochondria in T cells suggesting mtROS-dependent zincrelease of identified transcriptional regulators including ZFP36, RPL37A and CRIP2. In conclusion, this study complements knowledge on the mtROS signaling network and suggests zinc-dependent thiol switches as a mechanism of how mtROS affects transcription and translation in T cells.

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Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases

Cited by 51 publications

References 87 publications

Donor Heart Preservation with Hydrogen Sulfide: A Systematic Review and Meta-Analysis

Donor Heart Preservation with Hydrogen Sulfide: A Systematic Review and Meta-Analysis

Hydrogen Sulfide Metabolite, Sodium Thiosulfate: Clinical Applications and Underlying Molecular Mechanisms

Identification of mtROS-sensitive processes in activated CD4⁺T cells

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Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases

Cited by 51 publications

References 87 publications

Donor Heart Preservation with Hydrogen Sulfide: A Systematic Review and Meta-Analysis

Donor Heart Preservation with Hydrogen Sulfide: A Systematic Review and Meta-Analysis

Hydrogen Sulfide Metabolite, Sodium Thiosulfate: Clinical Applications and Underlying Molecular Mechanisms

Identification of mtROS-sensitive processes in activated CD4+T cells

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Identification of mtROS-sensitive processes in activated CD4⁺T cells