Hepatic Gene Expression Profiling of 5'AMP Induced Hypometabolism in Mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE23975 | GEO | 2012/06/20
SECONDARY ACCESSION(S): PRJNA130461
REPOSITORIES: GEO
Similar Datasets
Project description:Mice injected IP with 5'-AMP enter a hypometabolic state that is an induced hybernation (AIHM). Recovery from this AIHM is marked by reverse flip (RF) behavior Illumina arrays were used to profile control, AIHM and RF aminals in RNA prepared from the liver. Animals were injected with vehicle or 0.5 mg/g body weight 5'-adenosine monophosphate. At 6 hours (AIHM) or 12 hours (RF) animals were killed and total RNA prepared from the liver.
2012-06-19 | E-GEOD-23975 | biostudies-arrayexpress
Project description:There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5'-adenosine monophosphate (5'-AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5'-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism.
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Project description:Homeotherms maintain a stable internal body temperature despite changing environments. During energy deficiency, some species can cease to defend their body temperature and enter a hypothermic and hypometabolic state known as torpor. Despite recent advances in our understanding of thermoregulation, the precise neurons that coordinate these profound thermoregulatory and metabolic changes remain largely unknown. Here, we demonstrate that estrogen-sensitive neurons in the medial preoptic area (MPA) are key drivers of hypothermia and hypometabolism in mice. We find that selectively activating estrogen-sensitive MPA neurons was sufficient to drive a coordinated depression of metabolic rate and body temperature similar to torpor, as measured by body temperature, physical activity, indirect calorimetry, heart rate, and brain activity. Inducing torpor with a prolonged fast revealed larger and more variable calcium transients from estrogen-sensitive MPA neurons during bouts of hypothermia. Finally, selective ablation of estrogen-sensitive MPA neurons demonstrated that these neurons are required for the full expression of fasting-induced torpor. Together, these findings suggest a role for estrogen-sensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency.
2020-10-29 | GSE153350 | GEO
Project description:We have demonstrated that 5'-adenosine-monophosphate (5'-AMP) can be used to induce deep hypometabolism in mice and other non-hibernating mammals. This reversible 5'-AMP induced hypomatabolism (AIHM) allows mice to maintain a body temperature about 1°C above the ambient temperature for several hours before spontaneous reversal to euthermia. Our biochemical and gene expression studies suggested that the molecular processes involved in AIHM behavior most likely occur at the metabolic interconversion level, rather than the gene or protein expression level. To understand the metabolic processes involved in AIHM behavior, we conducted a non-targeted comparative metabolomics investigation at multiple stages of AIHM in the plasma, liver and brain of animals that underwent AIHM. Dozens of metabolites representing many important metabolic pathways were detected and measured using a metabolite profiling platform combining both LC-MS and GC-MS. Our findings indicate that there is a widespread suppression of energy generating metabolic pathways but lipid metabolism appears to be minimally altered. Regulation of carbohydrate metabolites appears to be the major way the animal utilizes energy in AIHM and during the following recovery process. The 5'-AMP administered has largely been catabolized by the time the animals have entered AIHM. During AIHM, the urea cycle appears to be functional, helping to avoid ammonia toxicity. Of all tissues studied, brain's metabolite flux is the least affected by AIHM.
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Project description:Streptococcus pneumoniae harbors two cyclic di-AMP (c-di-AMP) phosphodiesterases Pde1 and Pde2. Previously, we demonstrated that deletion of one or both of these proteins leads to growth retardation in culture media, defects in the bacterial stress response, and attenuation in mouse models of disease. All of these phenotypes are due to increased levels of c-di-AMP, since the nature and break down products of each protein are different, and mutations that lower c-di-AMP levels partially restore growth and stress tolerance in these mutants. However, how c-di-AMP mediates pneumococcal stress resistance and virulence is unknown. To establish how c-di-AMP affects the transcriptome, RNA-Seq analysis was employed to compare gene expression between wild-type and Δpde1Δpde2 (ST2734) pneumococci. Overall, the competence regulon was upregulated in the Δpde1Δpde2 mutant.
2018-04-18 | GSE113231 | GEO
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Project description:Cyclic di-AMP is an essential second messenger in many Gram-positive bacteria, including the model organism Bacillus subtilis. Here, we analyzed the transcriptome of a strain accumulating c-di-AMP in vivo. Our results demonstrate that accumulation of c-di-AMP affects the expression of several hundred genes, among them many mother-cell specific sporulation genes. Additionally, the two major biofilm operons, epsA-O and tapA-sipW-tasA, are affected. High levels of c-di-AMP abolish transcription of genes responsible for biofilm formation which in turn leads to a defect in complex colony formation in B. subtilis.
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Project description:Invertebrate antimicrobial peptides (AMPs) form the first line of defence against pathogenic microbes. Understanding AMP profiles in helminths, their importance to helminth biology, and how they shape microbial communities could reveal novel approaches for anthelmintic and/or antimicrobial development. In this study, we employed a LC-MS/MS peptidomics pipeline to validate a novel integrated homology- and computational-based pipeline for the discovery of helminth AMPs. Our peptidomics pipeline found 60 high-confidence PSMs correlating to 15 high-confidence novel AMP-LPs within Ascaris suum body-cavity fluid supporting the need for further characterisation of these peptides and their functions within helminths.
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