Project description:Physiological memories of environmental stress can serve to predict future environmental changes, allowing the organism to initiate protective mechanisms and survive. Although physiological memories, or bookmarks, of environmental stress have been described in a wide range of organisms, from bacteria to plants to humans, the mechanism by which these memories persist in the absence of stress is still largely unknown. We have discovered that C. elegans transiently exposed to low doses of hydrogen sulfide (H2S) survive subsequent exposure to otherwise lethal H2S concentrations and induce H2S-responsive transcripts more robustly than naïve controls. H2S bookmarking can occur at any developmental stage and persists through cell divisions and development but is erased by fasting. We show that maintenance of the H2S bookmark requires the SET-2 histone methyltransferase and the CoREST-like demethylase complex. We propose a model in which exposure to low doses of H2S generates a long-lasting, epigenetic memory by modulating H3K4me2 modifications at specific promoters. Understanding the fundamental aspects of H2S bookmarking in this tractable system can provide mechanistic insight into how environmental exposures are translated into the epigenetic landscape in animals.
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: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) has dramatic physiological effects on animals that are associated with improved survival in changing conditions. C. elegans grown in H2S are long-lived and thermotolerant (1). To begin to identify mechanisms by which adaptation to H2S effects fundamental physiological functions, we have defined transcriptional changes associated with the response to H2S. Using microarray analysis we observe rapid changes in the abundance of specific mRNAs. The number and magnitude of transcriptional changes increased with the duration of H2S exposure. Functional annotation suggests that genes associated with protein homeostasis are upregulated upon prolonged exposure to H2S. Previous work has shown that the hypoxia-inducible transcription factor, HIF-1, is required for survival in H2S (2). We show that hif-1 is required for all early transcriptional changes in H2S. However, our data suggest that other factors may also regulate transcriptional effects of H2S exposure, and we demonstrate that SKN-1, the C. elegans homologue of NRF2, is also required for some H2S-dependent changes in transcription. Moreover, we have found that, like hif-1, skn-1 is essential to survive exposure to H2S. Our results support a model in which HIF-1 and SKN-1 coordinate a broad transcriptional response to H2S, with the end result to affect a global reorganization of protein homeostasis networks. We propose that these transcriptional responses contribute to the effects of adaptation to H2S on lifespan and thermotolerance.
Project description:Hydrogen sulfide (H2S) is well known to cause irritation and damage to airway following inhalation, but the mechanism by which H2S contributes to airway toxicity is unclear. We apply transcriptomics to demonstrate the possible effects, obtain valuable information about adverse health effects following H2S exposure and to study the molecular mechanisms of the gas toxicity in trachea.
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: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:In this study we investigated the effect of two different agents producing hydrogen sulfide (H2S) on LPS-induced inflammatory mediators such as TNFa, NO and ROS. The agents (GYY4137 and sodium hydrosulfide) applied differ significantly by the kinetics of H2S release. In the investigation we compared the effects of H2S release on the LPS-induced inflammation exploring SH-SY5Y human neuroblastoma cell line and human promonocytic cell line, THP-1. Our data clearly show that both hydrogen sulfide producing agents significantly reduced the production of the investigated proinflammatory mediators when applied both before and after LPS administration. Furthermore, transcriptomic studies demonstrated that H2S release ameliorates the expression of multiple proinflammatory genes up-regulated due to LPS administration. However, the pattern of changes observed in transcriptome differs dramatically depending on the time of H2S release (before or after LPS-challenge).
Project description:Hydrogen sulfide (H2S) is well known to cause irritation and damage to airway following inhalation, but the mechanism by which H2S contributes to airway toxicity is unclear. We apply transcriptomics to demonstrate the possible effects, obtain valuable information about adverse health effects following H2S exposure and to study the molecular mechanisms of the gas toxicity in trachea.
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.