Hydrogen sulfide | EPFL Graph Search

Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The underground mine gas term for foul-smelling hydrogen sulfide-rich gas mixtures is stinkdamp. Swedish chemist Carl Wilhelm Scheele is credited with having discovered the chemical composition of purified hydrogen sulfide in 1777. The British English spelling of this compound is hydrogen sulphide, a spelling no longer recommended by the Royal Society of Chemistry or the International Union of Pure and Applied Chemistry. Hydrogen sulfide is toxic to humans and most other animals by inhibiting cellular respiration in a manner similar to hydrogen cyanide. When it is inhaled or its salts are ingested in high amounts, damage to organs occurs rapidly with symptoms ranging from breathing difficulties to convulsions and death. Despite this, the human body produ

Role of the cystathionine beta-synthase / H2S pathway in the development of cellular metabolic dysfunction and pseudohypoxia in down syndrome

Theodora Panagaki

Background: Overexpression of the transsulfuration enzyme cystathionine-beta-synthase (CBS), and overproduction of its product, hydrogen sulfide (H2S) are recognized as potential pathogenetic factors in Down syndrome (DS). The purpose of the study was to determine how the mitochondrial function and core metabolic pathways are affected by DS and how pharmacological inhibition of CBS affects these parameters. Methods: 8 human control and 8 human DS fibroblast cell lines have been subjected to bioenergetic and fluxomic and proteomic analysis with and without treatment with a pharmacological inhibitor of CBS. Results: DS cells exhibited a significantly higher CBS expression than control cells, and produced more H2S. They also exhibited suppressed mitochondrial electron transport and oxygen consumption and suppressed Complex IV activity, impaired cell proliferation and increased ROS generation. Inhibition of H2S biosynthesis with aminooxyacetic acid reduced cellular H2S, improved cellular bioenergetics, attenuated ROS and improved proliferation. C-13 glucose fluxomic analysis revealed that DS cells exhibit a suppression of the Krebs cycle activity with a compensatory increase in glycolysis. CBS inhibition restored the flux from glycolysis to the Krebs cycle and reactivated oxidative phosphorylation. Proteomic analysis revealed no CBS-dependent alterations in the expression level of the enzymes involved in glycolysis, oxidative phosphorylation and the pentose phosphate pathway. DS was associated with the dysregulation of several components of the autophagy network; CBS inhibition normalized several of these parameters. Conclusions: Increased H2S generation in DS promotes pseudohypoxia and contributes to cellular metabolic dysfunction by causing a shift from oxidative phosphorylation to glycolysis.

ELSEVIER2022

Caged luciferin probes for the bioluminescence imaging of nitroreductase and hydrogen sulfide in living animals

Anzhelika Vorobyeva

Molecular imaging advances our understanding of cellular and molecular functions within complex biological systems. The development of novel imaging probes that can be applied to answer fundamental biological questions, diagnose and monitor disease progression and the efficacy of therapy in vivo is essential to the field of molecular imaging. Bioluminescence imaging is a powerful technique that allows to study and follow biological processes of interest noninvasively in real-time in living animals. Activatable bioluminescent probes can be designed according to the target of interest and can provide imaging signal in response to the specific stimuli. A strategy called "caged luciferin" can be used to design new bioluminescent probes for imaging of enzymatic activity, the presence of small molecules or metabolite uptake in vivo. In Chapter 1 we present an overview of bioluminescence imaging, with a focus on firefly luciferase-luciferin system. The caged luciferin approach is discussed and examples of existing caged luciferin probes are presented. In Chapter 2 we describe the development of a bioluminescent probe for imaging of bacterial nitroreductase activity and show the potential for its application in different areas of research. Bacterial nitroreductases have been widely utilized in the gene-directed enzyme prodrug therapy (GDEPT) approach for cancer therapy that reached clinical trials. However, both preclinical and clinical development of NTR-based GDEPT systems has been hampered by the lack of imaging tools that allow in vivo evaluation of transgene expression. We developed the NTR caged luciferin (NCL) probe and demonstrated its application for sensitive bioluminescence imaging of NTR in vitro, in bacteria and cancer cells, as well as in vivo in mouse models of bacterial infection and NTR-expressing tumor xenografts. We anticipate that this probe would significantly accelerate the development of cancer therapy approaches based on GDEPT and other fields where evaluation of NTR expression is important. In Chapter 3 we describe the development of a bioluminescent probe for imaging of hydrogen sulfide (H2S) using the caged luciferin approach. The objective of the research was to develop a probe that can detect endogenously produced H2S noninvasively in real-time in living animals. We present a series of caged luciferin probes that were evaluated on their ability to rapidly and selectively detect H2S in in vitro assays, in cells and in bacterial culture. The two selected probes were applied for imaging of exogenous H2S in the gastrointestinal tract in living mice. We anticipate further applications of the best performing probe (Az-CL) for imaging of H2S production by gut microbiota in mice. In Chapter 4 we present the overall conclusion followed by the outlook and future perspectives.

EPFL2016

H2-fuelled microbial metabolism in Opalinus Clay

Rizlan Bernier-Latmani, Aislinn Ann Boylan, Niels Burzan, Luca Loreggian, Carla Perez Mon

In Switzerland, the Opalinus Clay formation is considered the most likely host rock for a deep geological repository for nuclear waste. In deep geological repositories, H2 is expected to be the most abundant gas formed from the degradation of waste and from metal corrosion. The microbial community present in Opalinus Clay is capable of utilizing H2 as an electron donor and sulfate as an electron acceptor to produce hydrogen sulfide. This could be problematic due to its potential for increasing the corrosion of metal waste canisters containing radioactive waste, however, the possible impacts of these processes on the clay rock have not been fully investigated. In this study, a series of microcosm experiments were set-up containing Opalinus Clay and porewater from the Mont Terri underground research laboratory (Switzerland) as an inoculum. Uninoculated microcosms were established to investigate abiotic processes. In the presence of clay, a higher aqueous sulfate concentration was detected than in those with only porewater present and this concentration decreased over time in the inoculated experiments. However, there was no evidence of hydrogen sulfide production in the aqueous phase. In all experiments with clay, there was an increase in aqueous Fe2+ concentrations with the highest concentrations found in uninoculated experiments. The sulfur speciation of the Opalinus Clay was analysed and the results of the inoculated sample suggested that hydrogen sulfide reacted with Fe2+, precipitating iron sulfide minerals. After the incubation period, the microbial community was dominated by the sulfate-reducing Desulfobulbaceae family. The study suggests that H2-fuelled, microbially-mediated sulfate reduction can affect the mineral composition within the Opalinus Clay due to the precipitation of iron sulfide minerals. These precipitation reactions may enhance the long-term integrity of the repository by removing corrosive hydrogen sulfide from solution when sufficient Fe2+ is available and so protecting the canisters containing the nuclear waste.

2019