Sulfur Dioxide: Endogenous Generation, Biological Effects, Detection, and Therapeutic Potential

Huang, Yaqian; Zhang, Heng; Lv, Boyang; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

doi:10.1089/ars.2021.0213

Cited by 49 publications

(37 citation statements)

References 93 publications

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“…Taken together, our data highlight the important protective role of SO 2 -dependent site-specific CypD S-sulphenylation in inhibiting mPTP opening and reducing apoptosis in cardiomyocytes ( Figure 5 ). Along with the in-depth studies on the biological effect of endogenous SO 2 and its mechanisms, the discovery of SO 2 -related prodrugs has become a hot topic for their potential therapeutic application ( Day et al, 2016 ; Wang and Wang, 2018 ; Huang et al, 2021b ). A variety of SO 2 prodrugs based on the different releasing mechanisms, such as thiol-activated SO 2 prodrug, thermally activated SO 2 prodrug, hydrolysis-based SO 2 prodrug, click reaction-based SO 2 prodrug, and esterase-sensitive SO 2 prodrug, developed to meet the different research requirement or clinical application in the future.…”

Section: Discussionmentioning

confidence: 99%

Sulphenylation of CypD at Cysteine 104: A Novel Mechanism by Which SO2 Inhibits Cardiomyocyte Apoptosis

Peng

Qiu

et al. 2022

Front. Cell Dev. Biol.

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Objectives: The study was designed to explore the role of endogenous gaseous signaling molecule sulfur dioxide (SO2) in the control of cardiomyocyte apoptosis and its molecular mechanisms.Methods: Neonatal mouse cardiac myocytes (NMCMs) and H9c2 cells were used in the cell experiments. The endogenous SO2 pathway including SO2 level and the expression of SO2-generating enzyme aspartate aminotransferase 1/2 (AAT1/2) were detected in NMCMs. The apoptosis of cardiomyocytes was examined by a TUNEL assay. The cleavage and the activity of apoptotic proteins caspase9 and caspase3 were measured. The content of ATP, the opening of mitochondrial permeability transition pore (mPTP), and the cytochrome c (cytc) leakage were detected by immunofluorescence. The sulphenylation of cyclophilin-D (CypD) was detected by biotin switch analysis. The four CypD mutant plasmids in which cysteine sites were mutated to serine were constructed to identify the SO2-affected site in vitro.Results: ISO down-regulated the endogenous SO2/AAT pathway of cardiomyocytes in association with a significant increase in cardiomyocyte apoptosis, demonstrated by the increases in apoptosis, cleaved-caspase3/caspase3 ratio, and caspase3 activity. Furthermore, ISO significantly reduced ATP production in H9c2 cells, but the supplement of SO2 significantly restored the content of ATP. ISO stimulated mPTP opening, resulting in an increase in the release of cytc, which further increased the ratio of cleaved caspase9/caspase9 and enhanced the protein activity of caspase9. While, the supplementation of SO2 reversed the above effects. Mechanistically, SO2 did not affect CypD protein expression, but sulphenylated CypD and inhibited mPTP opening, resulting in an inhibition of cardiomyocyte apoptosis. The C104S mutation in CypD abolished SO2-induced sulphenylation of CypD, and thereby blocked the inhibitory effect of SO2 on the mPTP opening and cardiomyocyte apoptosis.Conclusion: Endogenous SO2 sulphenylated CypD at Cys104 to inhibit mPTP opening, and thus protected against cardiomyocyte apoptosis.

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Section: Discussionmentioning

confidence: 99%

Sulphenylation of CypD at Cysteine 104: A Novel Mechanism by Which SO2 Inhibits Cardiomyocyte Apoptosis

Peng

Qiu

et al. 2022

Front. Cell Dev. Biol.

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“…

absorbed by roots is activated by ATP sulfurylase (ATPS), producing adenosine 5′-phosphosulfate (APS), which is transformed into

(main form of SO 2 in solution) by APS reductase (APR) using glutathione (GSH) as reducing agent ( Li et al, 2020 ). In addition, cysteine (Cys) can change into cysteine sulfinate (Cts) by the catalysis of cysteine dioxygenase (CDO), and then produce β-sulfinylpyruvate (SP), which automatically form SO 2 without any enzyme catalysis and release pyruvate (Pyr; Yu et al, 2020 ; Huang et al, 2022 ). Also, SO 2 can be released from hydrogen sulfide (H 2 S) and its derivant thiosulfate (TS) under the catalysis of NOX, sulfide oxidase (SO), and TS sulfurtransferase (TST), respectively ( Li et al, 2009 ).…”

Section: Metabolism Of Somentioning

confidence: 99%

“…Cys is a common precursor for biosynthesis of numerous biological molecules such as GSH, phytochelatin (PC), phytoalexins (PA), cystathionine (Cyst), homocystine (Hcy), methionine (Met), ethylene (ETH), and glucosinolate (GSL; Figure 1 ). GSH, as an important reducing agent in plant cells, which can be synthesized from Cys under the successive catalysis of γ-glutamycysteine synthetase (γ-ES) and GSH synthesis (GS; Yu et al, 2020 ; Huang et al, 2022 ). GSH and its oxidized form (GSSG) can mutually convert by dehydroascorbate reductase (DHAR) and glutathione reductase (GR) using dehydroascorbate and NADPH as electron acceptor and electron donor, respectively ( Bartoli et al, 2017 ).…”

Section: Metabolism Of Somentioning

confidence: 99%

Sulfur Dioxide: An Emerging Signaling Molecule in Plants

Chen

2022

Front. Plant Sci.

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Sulfur dioxide (SO2) has long been viewed as toxic gas and air pollutant, but now is being verified as a signaling molecule in mammalian cells. SO2 can be endogenously produced and rapidly transformed into sulfur-containing compounds (e.g., hydrogen sulfide, cysteine, methionine, glutathione, glucosinolate, and phytochelatin) to maintain its homeostasis in plant cells. Exogenous application of SO2 in the form of gas or solution can trigger the expression of thousands of genes. The physiological functions of these genes are involved in the antioxidant defense, osmotic adjustment, and synthesis of stress proteins, secondary metabolites, and plant hormones, thus modulating numerous plant physiological processes. The modulated physiological processes by SO2 are implicated in seed germination, stomatal action, postharvest physiology, and plant response to environmental stresses. However, the review on the signaling role of SO2 in plants is little. In this review, the anabolism and catabolism of SO2 in plants were summarized. In addition, the signaling role of SO2 in seed germination, stomatal movement, fruit fresh-keeping, and plant response to environmental stresses (including drought, cold, heavy metal, and pathogen stresses) was discussed. Finally, the research direction of SO2 in plants is also proposed.

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“…Most of their functions do not occur when they are in a gaseous state, although they are collectively termed gaseous mediators [ 9 , 10 , 11 , 12 , 13 ]. In recent years, gases, such as sulfur dioxide, hydrogen cyanide and methane, have emerged as potential novel gaseous mediators [ 8 , 14 , 15 , 16 ]; however, to date, only three small, chemically reactive and freely permeable molecules comprise the novel signaling gaseous mediator family, which includes nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H 2 S) [ 8 ]. Importantly, NO, CO and H 2 S harbor several features in common.…”

Section: Introductionmentioning

confidence: 99%

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Zhu

Chambers

Zeng

et al. 2022

IJMS

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Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.

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Sulfur Dioxide: Endogenous Generation, Biological Effects, Detection, and Therapeutic Potential

Cited by 49 publications

References 93 publications

Sulphenylation of CypD at Cysteine 104: A Novel Mechanism by Which SO2 Inhibits Cardiomyocyte Apoptosis

Sulphenylation of CypD at Cysteine 104: A Novel Mechanism by Which SO2 Inhibits Cardiomyocyte Apoptosis

Sulfur Dioxide: An Emerging Signaling Molecule in Plants

Gases in Sepsis: Novel Mediators and Therapeutic Targets

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