Fluorescent Probes and Selective Inhibitors for Biological Studies of Hydrogen Sulfide- and Polysulfide-Mediated Signaling

Takano, Yoko; Echizen, Honami; Hanaoka, Kenjiro

doi:10.1089/ars.2017.7070

Cited by 49 publications

(23 citation statements)

References 93 publications

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“…Sulfhydration has been proposed as a mode of H2S action in which H2S adds sulfur atoms to cysteine residues of target proteins to induce conformational changes, leading to modification of target protein activity [30]. According to the amino acid sequences available in PubMed, there are nine cysteines in the Hrd1 sequence.…”

Section: Discussionmentioning

confidence: 99%

Exogenous H2S Induces Hrd1 S-sulfhydration and Prevents CD36 Translocation via VAMP3 Ubiquitylation in Diabetic Hearts

Wang

et al. 2020

Aging and disease

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Hydrogen sulfide (H2S) plays physiological roles in vascular tone regulation, cytoprotection, and ATP synthesis. HMG-CoA reductase degradation protein (Hrd1), an E3 ubiquitin ligase, is involved in protein trafficking. H2S may play a role in controlling fatty acid uptake in diabetic cardiomyopathy (DCM) in a manner correlated with modulation of Hrd1 S-sulfhydration; however, this role remains to be elucidated. The aim of the present study was to examine whether H2S can attenuate lipid accumulation and to explain the possible mechanisms involved in the regulation of the H2S-Hrd1/VAMP3 pathway. Db/db mice and neonatal rat cardiomyocytes treated with high glucose, palmitate and oleate were used as animal and cellular models of type 2 diabetes, respectively. The expression of cystathionine-γ-lyase (CSE), Hrd1, CD36 and VAMP3 was detected by Western blot analysis. In addition, Hrd1 was mutated at Cys115, and Hrd1 S-sulfhydration was examined using an S-sulfhydration assay. VAMP3 ubiquitylation was investigated by immunoprecipitation. Lipid droplet formation was tested by TEM, BODIPY 493/503 staining and oil red O staining. The expression of CSE and Hrd1 was decreased in db/db mice compared to control mice, whereas CD36 and VAMP3 expression was increased. NaHS administration reduced droplet formation, and exogenous H2S restored Hrd1 expression, modified Ssulfhydration, and decreased VAMP3 expression in the plasma membrane. Using LC-MS/MS analysis, we identified 85 proteins with decreased ubiquitylation, including 3 vesicle-associated membrane proteins, in the cardiac tissues of model db/db mice compared with NaHS-treated db/db mice. Overexpression of Hrd1 mutated at Cys115 diminished VAMP3 ubiquitylation, whereas it increased CD36 and VAMP3 expression and droplet formation. siRNA-mediated Hrd1 deletion increased the expression of CD36 in the cell membrane. These findings suggested that H2S regulates VAMP3 ubiquitylation via Hrd1 S-sulfhydration at Cys115 to prevent CD36 translocation in diabetes.

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Section: Discussionmentioning

confidence: 99%

Exogenous H2S Induces Hrd1 S-sulfhydration and Prevents CD36 Translocation via VAMP3 Ubiquitylation in Diabetic Hearts

Wang

et al. 2020

Aging and disease

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“…AIK is composed from the following inducers – Actinomycin D, Camptothecin, Cycloheximide, Dexamethasone, and Etoposide. Cells were treated also with D,L- propargyl glycine (PGG; 1 mM [ 21 , 22 ]; Cayman Chemicals), O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA; 10 μM [ 23 ]; Sigma Aldrich), or H 2 S producing enzymes were silenced by the procedure described in Hudecova et al [ 2 ] using SMARTpool ONTARGETplus CBS siRNA (Dharmacon, L-008617-00-0005), SMARTpool ON-TARGETplus Cth siRNA (Dharmacon, L-064123-01-0005), SMARTpool ONTARGETplus MPST siRNA (Dharmacon, L-010119-00-0005). As a negative control (scrambled), ON-TARGETplus NON-targeting Pool siRNAs were used (Dharmacon, USA).…”

Section: Methodsmentioning

confidence: 99%

Endogenous H2S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma

et al. 2018

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BackgroundKnowledge about the expression and thus a role of enzymes that produce endogenous H2S - cystathionine-β-synthase, cystathionine γ-lyase and mercaptopyruvate sulfurtransferase - in renal tumors is still controversial. In this study we aimed to determine the expression of these enzymes relatively to the expression in unaffected part of kidney from the same patient and to found relation of these changes to apoptosis. To evaluate patient’s samples, microarray and immunohistochemistry was used.MethodsTo determine the physiological importance, we used RCC4 stable cell line derived from clear cell renal cell carcinoma, where apoptosis induction by a mixture of five chemotherapeutics with/without silencing of H2S-producing enzymes was detected. Immunofluorescence was used to determine each enzyme in the cells.ResultsIn clear cell renal cell carcinomas, expression of H2S-producing enzymes was mostly decreased compared to a part of kidney that was distal from the tumor. To evaluate a potential role of H2S-producing enzymes in the apoptosis induction, we used RCC4 stable cell line. We have found that silencing of cystathionine-β-synthase and cystathionine γ-lyase prevented induction of apoptosis. Immunofluorescence staining clearly showed that these enzymes were upregulated during apoptosis in RCC4 cells.ConclusionBased on these results we concluded that in clear cell renal cell carcinoma, reduced expression of the H2S-producing enzymes, mainly cystathionine γ-lyase, might contribute to a resistance to the induction of apoptosis. Increased production of the endogenous H2S, or donation from the external sources might be of a therapeutic importance in these tumors.

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“…Nucleophilic-based fluorescent probe for H 2 S detection is designed based on the strong nucleophilic HS − hydrolyzed from H 2 S at physiological pH (pH = 7.4) [ 86 ]. Qian et al used this concept to develop fluorescent probes, SFP-1 and SFP-2, which allowed fluorescence switching via HS − addition to aldehyde and underwent an intermolecular Michael addition to unsaturated acrylate ester to form a thioacetal, producing stable tetrahydrothiophene with strong fluorescence [ 87 ].…”

Section: H 2 S Measurementsmentioning

confidence: 99%

The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease

Wen

Wang

Zhu

2018

Oxidative Medicine and Cellular Longevity

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The recognition of hydrogen sulfide (H2S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H2S is produced from L-cysteine by enzymes of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H2S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson's reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H2S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H2S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.

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Fluorescent Probes and Selective Inhibitors for Biological Studies of Hydrogen Sulfide- and Polysulfide-Mediated Signaling

Cited by 49 publications

References 93 publications

Exogenous H2S Induces Hrd1 S-sulfhydration and Prevents CD36 Translocation via VAMP3 Ubiquitylation in Diabetic Hearts

Exogenous H2S Induces Hrd1 S-sulfhydration and Prevents CD36 Translocation via VAMP3 Ubiquitylation in Diabetic Hearts

Endogenous H2S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma

The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease

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