Efficient inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by sulfuration with solubilized elemental sulfur

Bolton, Sarah G.; Pluth, Michael D.

doi:10.1016/j.freeradbiomed.2022.03.032

Cited by 8 publications

(7 citation statements)

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“…GAPDH is another key enzyme in the glycolytic pathway, and is thus involved in the energy metabolism of cells. GAPDH is expressed at high levels in almost all tissues (Bolton & Pluth, 2022).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the glycolysis pathway in Enterocytozoon hepatopenaei after germination promotion and inhibition

Zhu

Dong

feng³

et al. 2022

Preprint

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Enterocytozoon hepatopenaei (EHP) is an important factor limiting the growth of Penaeus vannamei. Its simple transmission route and lack of effective control drugs often lead to great losses for the shrimp aquaculture industry. In this study, some basic information of EHP was provided, including EHP spore purification, germination promoting treatment, quantification determination of the key genes expression, and the activities determination of key enzymes in glycolysis pathway at the stage of spore germination. The result showed that light microscopic and scanning electron microscopic analyses confirmed KOH promoted germination. The expression of the glyceraldehyde 3-phosphate dehydrogenase gene was stable, with high-level expression in treatment groups. Hexokinase gene expression and enzyme activity increased after promoting germination treatment. These findings indicated that the glycolytic pathway is enhanced during EHP germination. The results suggest that we can prevent EHP from invading host cells by attempting to block the energy supply.

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Section: Discussionmentioning

confidence: 99%

Analysis of the glycolysis pathway in Enterocytozoon hepatopenaei after germination promotion and inhibition

Zhu

Dong

feng³

et al. 2022

Preprint

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“…Using a 50 wt % solution of 2HPβ resulted in up to 2 mM S 8 in water, and the resultant 2HPβ/S 8 complex could be used to decrease NO 2 – production in Raw 264.7 macrophage cells stimulated with proinflammatory lipopolysaccharides . Similarly, treatment of isolated GAPDH enzyme with 2HPβ/S 8 modulates enzyme activity through sulfuration of a key GAPDH Cys residue . Although both of these examples suggest that solubilized S 8 may be bioavailable, the mechanism of S 8 activation and the interplay between soluble sulfane sulfur species remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…41 Similarly, treatment of isolated GAPDH enzyme with 2HPβ/S 8 modulates enzyme activity through sulfuration of a key GAPDH Cys residue. 42 Although both of these examples suggest that solubilized S 8 may be bioavailable, the mechanism of S 8 activation and the interplay between soluble sulfane sulfur species remain unclear. Understanding the mechanism by which complementary host molecules can solubilize and activate S 8 would provide important insights into the biological sulfur redox economy.…”

Section: ■ Introductionmentioning

confidence: 99%

Supramolecular Activation of S₈ by Cucurbiturils in Water and Mechanism of Reduction to H₂S by Thiols: Insights into Biological Sulfane Sulfur Trafficking

2022

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Reactive sulfur species (RSS) play critical roles in diverse chemical environments. Molecules containing sulfane sulfur (S0) have emerged as key species involved in cellular redox buffering as well as RSS generation, translocation, and action. Using cucurbit[7]uril (CB[7]) as a model hydrophobic host, we demonstrate here that S8 can be encapsulated to form a 1:1 host guest complex, which was confirmed by solution state experiments, mass spectrometry, and X-ray crystallography. The solid state structure of CB[7]/S8 shows that the encapsulated S8 is available to nucleophiles through the carbonyl portals of the host. Treatment of CB[7]/S8 with thiols results in efficient reduction of S8 to H2S in water at physiological pH. We establish that encapsulated S8 is attacked by a thiol within the CB[7] host and that the resultant soluble hydropolysulfide is ejected into solution, where it reacts further with thiols to generate soluble sulfane sulfur carriers and ultimately H2S. The formation of these intermediate is supported by observed kinetic saturation behavior, competitive inhibition experiments, and alkylative trapping experiments. We also demonstrate that CB[7]/S8 can be used to increase sulfane sulfur levels in live cells using fluorescence microscopy. More broadly, this work suggests a general activation mechanism of S8 by hydrophobic motifs, which may be applicable to proteins, membranes, or other bimolecular compartments that could transiently bind and solubilize S8 to promote reaction with thiols to solubilize and shuttle S8 back into the redox labile sulfane sulfur pool. Such a mechanism would provide an attractive manifold in which to understand the RSS translocation and trafficking.

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“…39 Similarly, treatment of isolated GAPDH enzyme with 2HPβ/S 8 modulates enzyme activity through sulfuration of a key GAPDH Cys residue. 40 Although both of these examples suggest that solubilized S 8 may be bioavailable, the mechanism of S 8 and the interplay between soluble sulfane sulfur species remains unclear. Understanding the mechanism by which complementary host molecules can solubilize and activate S 8 would provide important insights into the biological sulfur redox economy.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Activation of S8 by Cucurbiturils in Water and Mechanism of Reduction to H2S by Thiols: Insights into Biological Sulfane Sulfur Trafficking

Garcia¹,

Zakharov²,

Pluth³

2022

Preprint

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Reactive sulfur species (RSS) play critical roles in diverse chemical environments. Molecules containing sulfane sulfur (S0) have emerged as key species involved in cellular redox buffering as well as RSS generation, translocation, and action. Using cucurbit[7]uril (CB[7]) as a model hydrophobic host, we demonstrate here that S8 can be encapsulated to form a 1:1 host guest complex, which was confirmed by solution state experiments, mass spectrometry, and X-ray crystallography. The solid state structure of CB[7]/S¬8 shows that the encapsulated S¬8 is available to nucleophiles through the carbonyl portals of the host. Treatment of CB[7]/S8 with thiols results in efficient reduction of S8 to H2S in water at physiological pH. We establish that encapsulated S8 is attacked by a thiol within the CB[7] host and that the resultant soluble hydropolysulfide is ejected into solution, where it reacts further with thiols to generate soluble sulfane sulfur carriers and ultimately H2S. The formation of these intermediate is supported by observed kinetic saturation behavior, competitive inhibition experiments, and alkylative trapping experiments. We also demonstrate that CB[7]/S8 can be used to increase sulfane sulfur levels in live cells using fluorescence microscopy. More broadly, this work suggests a general activation mechanism of S8 by hydrophobic motifs, which may be applicable to proteins, membranes, or other bimolecular compartments that could transiently bind and solubilize S8 to promote reaction with thiols to solubilize and shuttle S8 back into the redox labile sulfane sulfur pool. Such a mechanism would provide an attractive manifold in which to understand the RSS translocation and trafficking.

show abstract

Efficient inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by sulfuration with solubilized elemental sulfur

Cited by 8 publications

References 50 publications

Analysis of the glycolysis pathway in Enterocytozoon hepatopenaei after germination promotion and inhibition

Analysis of the glycolysis pathway in Enterocytozoon hepatopenaei after germination promotion and inhibition

Supramolecular Activation of S₈ by Cucurbiturils in Water and Mechanism of Reduction to H₂S by Thiols: Insights into Biological Sulfane Sulfur Trafficking

Supramolecular Activation of S8 by Cucurbiturils in Water and Mechanism of Reduction to H2S by Thiols: Insights into Biological Sulfane Sulfur Trafficking

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