A cysteine-triggered fluorogenic donor base on native chemical ligation for tracking H2S delivery in vivo

The Analyst ◽  
2021 ◽  
Author(s):  
Li Li ◽  
Zhenmei Lin ◽  
Yongfang Cheng ◽  
Yaoping Tang ◽  
Ziqian Zhang
Keyword(s):  
Hydrogen Sulfide ◽  
Native Chemical Ligation ◽  
Chemical Ligation ◽  
Molecular Tool ◽  
Biological Studies ◽  
Exogenous Source

Hydrogen sulfide (H2S) donor is a fundamental molecular tool used as the exogenous source in related biological studies and therapies. However, controllable and fluorescence visual H2S donor is still lack....

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Cell Model ◽  
Site Directed Mutagenesis ◽  
Critical Event ◽  
Hypertensive Rats ◽  
Pulmonary Artery Endothelial Cell

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

ADT-OH, a Hydrogen Sulfide-Releasing Donor, Induces Apoptosis of Melanoma Cells and Inhibits Melanoma Development In Vivo

2019 ◽  
Author(s):  
Fangfang Cai ◽  
Nini Cao ◽  
Xiangyu Zhang ◽  
Jia Liu ◽  
Huangru Xu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Melanoma Cells

scholarly journals H2S in acute lung injury: a therapeutic dead end(?)

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Tamara Merz ◽  
Nicole Denoix ◽  
Martin Wepler ◽  
Holger Gäßler ◽  
David A. C. Messerer ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Circulatory Shock ◽  
Therapeutic Window ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Clinical Reality ◽  
Dead End

AbstractThis review addresses the plausibility of hydrogen sulfide (H2S) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The review discusses how the narrow therapeutic window and width, and potentially toxic effects, the route, dosing, and timing of administration all have to be balanced out very carefully. The development of standardized methods to determine in vitro and in vivo H2S concentrations, and the pharmacokinetics and pharmacodynamics of H2S-releasing compounds is a necessity to facilitate the safety of H2S-based therapies. We suggest the potential of exploiting already clinically approved compounds, which are known or unknown H2S donors, as a surrogate strategy.

scholarly journals Autocatalytic and oscillatory reaction networks that form guanidines and products of their cyclization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander I. Novichkov ◽  
Anton I. Hanopolskyi ◽  
Xiaoming Miao ◽  
Linda J. W. Shimon ◽  
Yael Diskin-Posner ◽  
...  
Keyword(s):  
Chemical Cues ◽  
Native Chemical Ligation ◽  
Reaction Networks ◽  
Oscillatory Reaction ◽  
Experimental Conditions ◽  
Chemical Ligation ◽  
Chemical Systems ◽  
Life On Earth ◽  
Emergence Of Life ◽  
Equilibrium Chemical

AbstractAutocatalytic and oscillatory networks of organic reactions are important for designing life-inspired materials and for better understanding the emergence of life on Earth; however, the diversity of the chemistries of these reactions is limited. In this work, we present the thiol-assisted formation of guanidines, which has a mechanism analogous to that of native chemical ligation. Using this reaction, we designed autocatalytic and oscillatory reaction networks that form substituted guanidines from thiouronium salts. The thiouronium salt-based oscillator show good stability of oscillations within a broad range of experimental conditions. By using nitrile-containing starting materials, we constructed an oscillator where the concentration of a bicyclic derivative of dihydropyrimidine oscillates. Moreover, the mixed thioester and thiouronium salt-based oscillator show unique responsiveness to chemical cues. The reactions developed in this work expand our toolbox for designing out-of-equilibrium chemical systems and link autocatalytic and oscillatory chemistry to the synthesis of guanidinium derivatives and the products of their transformations including analogs of nucleobases.

Recent progress in the development of sensing systems for in vivo detection of biological hydrogen sulfide

2021 ◽  
pp. 109451
Author(s):  
Jie Li ◽  
Zhe Su ◽  
Changmin Yu ◽  
Yan Yuan ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Recent Progress ◽  
Sensing Systems ◽  
In Vivo Detection
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