Project description:Although sulfur-rich thermal waters have ancestrally been used in the context of dermatological conditions, a global mapping of the molecular effects exerted by H2S on human keratinocytes is still lacking. To fill this knowledge gap, we subjected cultured human keratinocytes to distinct amounts of the non-gaseous hydrogen sulfur donor NaHS. We first checked that H2S accumulated in the cytoplasm of keratinocytes under our experimental conditions andused a combination of proteomics, genomics and biochemical approaches to unravel functionally relevant H2S targets in human keratinocytes. We found that the identified targets fall into two main categories: (i) the oxidative stress response molecules superoxide dismutase 2 (SOD2), NAD(P)H quinone dehydrogenase 1 (NQO1) and culin 3 (CUL3) and (ii) the chemokines interleukin-8 (IL-8) and CXCL2. Interestingly, NaHS also stimulated the caspase-1 inflammasome pathway, leading to increased secretion of the pro-inflammatory molecule interleukin-18 (IL-18). Interestingly, the secretion of interleukin-1 beta (IL-1?) was only modestly impacted by NaHS exposure despite a significant accumulation of IL-1? pro-form. Finally, we observed that NaHS significantly hampered the growth of human keratinocyte progenitors and stem cells cultured under clonogenic conditions or as epidermal cell sheets. We conclude that H2S exerts specific molecular effects on normal human keratinocytes.
Project description:In the present paper, we report on the pan-genomics and pan-proteomics analysis of cultured epithelial sheets of human keratinocyte progenitors. Our results notably show that NaHS stimulates the secretion of specific pro-inflammatory cytokines and promotes the synthesis of molecules involved in antioxidative mechanisms
Project description:Interventions: Case series:nill;The control group:nill
Primary outcome(s): Hydrogen sulfide;Pathological diagnosis
Study Design: Case-Control study
Project description:Stress response of Methylococcus capsulatus str.Bath toward hydrogen sulfide (H2S) was investigated via physiological study and transcriptomic profiling. M. capsulatus (Bath) can grow and tolerate up to 0.75%vol H2S in headspace. Vast change in pH suggests biological relevant sulfide oxidation. Dozens of H2S-sensitive genes were identified from comparison of cell transcriptome in different H2S concentrations. Mc sulfide quinone reductase (SQR) and persulfide dioxygenase were found to be active during sulfide detoxification. Moreover, xoxF, a novel lanthanide(Ln)-dependent methanol dehydrogenase (MDH) was overexpressed in H2S while mxaF, a calcium-dependent MDH, was down-regulated, and such MDH switch phenomenon is also well known to be induced by addition of lanthanide via an as-yet-unknown mechanism. Activities in quorum sensing and RND efflux pump also suggest their role in sulfide detoxification, and might provide insight on the xoxF/mxaF switch mechanism.
Project description:The aim of this experiment was to determine how exposure of Hydrogen sulfide impacts gene expression in Mycobacterium tuberculosis. RNA was isolated from actively growing mycobacterial cells (0.6-0.8 OD600) using Trizol according to established protocols (27). Briefly, cells were exposed to 25 µM GYY4137 for 1 hr under carefully controlled conditions (n=3/group) and RNA isolated. Unexposed cells received spent GYY4137 (without any capacity to produce Hydrogen sulfide).
Project description:Hydrogen sulfide (H2S) as an important gasotransmitter has fundamental roles in human diseases. The cellular effect of H2S has received lots of attention recently. H2S can affect ion channels, transcription factors and kinase in mammals. The mechanism of cellular effect of H2S is not completely understood. We used fission yeast as a model organism to study the global transcriptional profile in response to H2S by microarray.
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated.
Project description:As one of the most important environmental factors, heat stress (HS) has been found to affect various biological activities of organisms such as growth, signal transmission, primary metabolism and secondary metabolism. Ganoderma lucidum has become a potential model system for evaluating how environmental factors regulate the secondary metabolism of basidiomycetes. Previous research showed that HS can induce the biosynthesis of ganoderic acids (GAs). In this study, we found the existence of hydrogen sulfide in Ganoderma lucidum; moreover, HS increased GAs biosynthesis and could affect the hydrogen sulfide content. We found that sodium hydrosulfide (NaHS), an exogenous donor of hydrogen sulfide, could revert the increased GAs biosynthesis elicited by HS. This result indicated that an increased content of hydrogen sulfide, within limits, was associated with HS-induced GAs biosynthesis. Our results further showed that the GAs content was increased in CBS-silenced strains and could be reverted to WT strain levels by the addition of NaHS. Transcriptomic analyses indicated that that H2S can affect various intracellular signal pathways and physiological processes in G. lucidum. Further studies showed that H2S could affect the intracellular calcium concentration and thus regulate the biosynthesis of GAs. This study demonstrated that hydrogen sulfide is involved in the regulation of secondary metabolic processes induced by heat stress in filamentous fungi.
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated. The global transcriptome of control nematodes (raised using standardized laboratory conditions) was compared to nematodes exposed to 100 uM GYY4137 (morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate), a slow releasing H2S donor drug.
Project description:Hydrogen sulfide (H2S), present in abundance in the mammalian brain, has recently been demonstrated to induce a dose- and time-dependent apoptotic-necrotic continuum in murine primary cortical neurons, which was successfully attenuated upon application of N-methyl-D-aspartate (NMDA) receptor antagonist. The current study focused on gaining an insight into the molecular mechanisms of H2S–mediated neuronal death pertaining to NMDA receptors activation through global gene expression comparisons.