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Metformin preconditioning protects against myocardial stunning and preserves mitochondrial dynamics and protein translation in a mouse model of cardiac arrest

ABSTRACT: We compare microarray data from homogenized left ventricles of the heart at 24 hours after sham surgey vs 8-min potassium chloride induced sudden cardiac arrest and resuscitation

ORGANISM(S): Mus musculus

PROVIDER: GSE176494 | GEO | 2021/08/01

REPOSITORIES: GEO

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Metformin preconditioning protects against myocardial stunning and preserves protein translation in a mouse model of cardiac arrest.

Project description:Cardiac arrest (CA) causes high mortality due to multi-system organ damage attributable to ischemia-reperfusion injury. Recent work in our group found that among diabetic patients who experienced cardiac arrest, those taking metformin had less evidence of cardiac and renal damage after cardiac arrest when compared to those not taking metformin. Based on these observations, we hypothesized that metformin's protective effects in the heart were mediated by AMPK signaling, and that AMPK signaling could be targeted as a therapeutic strategy following resuscitation from CA. The current study investigates metformin interventions on cardiac and renal outcomes in a non-diabetic CA mouse model. We found that two weeks of metformin pretreatment protects against reduced ejection fraction and reduces kidney ischemia-reperfusion injury at 24 h post-arrest. This cardiac and renal protection depends on AMPK signaling, as demonstrated by outcomes in mice pretreated with the AMPK activator AICAR or metformin plus the AMPK inhibitor compound C. At this 24-h time point, heart gene expression analysis showed that metformin pretreatment caused changes supporting autophagy, antioxidant response, and protein translation. Further investigation found associated improvements in mitochondrial structure and markers of autophagy. Notably, Western analysis indicated that protein synthesis was preserved in arrest hearts of animals pretreated with metformin. The AMPK activation-mediated preservation of protein synthesis was also observed in a hypoxia/reoxygenation cell culture model. Despite the positive impacts of pretreatment in vivo and in vitro, metformin did not preserve ejection fraction when deployed at resuscitation. Taken together, we propose that metformin's in vivo cardiac preservation occurs through AMPK activation, requires adaptation before arrest, and is associated with preserved protein translation.

| S-EPMC10327679 | biostudies-literature

Transcription profiling by tiling array of Potassium availability triggers Mycobacterium tuberculosis transition to, and resuscitation from, non-culturable (dormant) states

Project description:Dormancy in non-sporulating bacteria is an interesting and underexplored phenomenon with significant medical implications. In particular, latent tuberculosis may result from the maintenance of Mycobacterium tuberculosis bacilli in non-replicating states in infected individuals. Uniquely, growth of M. tuberculosis in aerobic conditions in potassium-deficient media resulted in the generation of bacilli that were non-culturable (NC) on solid media but detectable in liquid media. These bacilli were morphologically distinct and tolerant to cell-wall-targeting antimicrobials. Bacterial counts on solid media quickly recovered after washing and incubating bacilli in fresh resuscitation media containing potassium. This resuscitation of growth occurred too quickly to be attributed to M. tuberculosis replication. Transcriptomic and proteomic profiling through adaptation to, and resuscitation from, this NC state revealed a switch to anaerobic respiration and a shift to lipid and amino acid metabolism. High concordance with mRNA signatures derived from M. tuberculosis infection models suggests that analogous NC mycobacterial phenotypes may exist during disease and may represent unrecognized populations in vivo. Resuscitation of NC bacilli in potassium-sufficient media was characterized by time-dependent activation of metabolic pathways in a programmed series of processes that probably transit bacilli through challenging microenvironments during infection. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-151]

2015-02-25 | E-BUGS-151 | biostudies-arrayexpress

Expression analysis of big neurospheres generated in vitro

Project description:Expression analysis of neurospheres generated in vitro treated by potassium chloride (KCl) and norepinephrine Neurospheres generated in vitro were treated with norepinephrine or potassium chloride. Gene expression analysis was then carried out to identify genes that are up or down regulated due to chemical treatment.

2015-06-12 | E-GEOD-67304 | biostudies-arrayexpress

Expression analysis of big neurospheres generated in vitro

Project description:Expression analysis of neurospheres generated in vitro treated by potassium chloride (KCl) and norepinephrine

2015-06-12 | GSE67304 | GEO

Enhancer RNAs make multivalent interactions with NELF to stimulate Pol II pause release [Exo-seq]

Project description:5’ ExoSeq of total RNA (rRNA & signal recognition particle RNA depleted) from mouse cortical neurons before and after membrane depolarization by potassium chloride (KCl).

2022-03-08 | GSE163111 | GEO

RNA-seq datasets for "Temporally Specific Gene Expression and Chromatin Remodeling Programs Regulate a Conserved Pdyn Enhancer" [RNA-seq]

Project description:This dataset contains RNA-seq results from rat embryonic striatal neuronal cultures treated with either vehicle (complete Neurobasal media) or potassium chloride (10mM) for 4 h.

2023-08-07 | GSE233752 | GEO

Protein phosphorylation in depolarized synaptosomes

Project description:Rat brain synaptosomes were used to study effects of calcium and synaptic vesicle cycling on protein phosphorylation following potassium chloride-induced depolarization.

2021-02-17 | PXD020564 | Pride

RNA-seq datasets for "Temporally Specific Gene Expression and Chromatin Remodeling Programs Regulate a Conserved Pdyn Enhancer"

Project description:This dataset contains Assay for Transposase-Accessible Chromatin (ATAC) sequencing results from rat embryonic striatal neuronal cultures treated with either vehicle (complete Neurobasal media) or potassium chloride (10mM) for 4 h.

2023-08-07 | GSE233368 | GEO

Expression analysis of neurospheres generated in vitro

Project description:Neurospheres generated in vitro were treated with non-epinephrine or potassium chloride. Gene expression analysis was then carried out to identify genes that are up or down regulated due to chemical treatement.

2014-06-20 | GSE57440 | GEO

Transcriptomic changes induced in yeast cells by the lack of potassium in the medium

Project description:Potassium is the major intracellular cation in S. cerevisiae, which can be concentrated up to 200-300 mM even from relatively low potassium (< 1 mM) environments. This is achieved by mean of a high affinity K+-transport system encoded by the genes TRK1 and TRK2. Recently, our group became interested in the effects of sudden shortage of extracellular potassium. Transcriptomic analysis indicates that lack of potassium drastically alters sulfur metabolism (mainly Met and Cys metabolism), triggers an oxidative stress response and activates the mitochondrial retrograde pathway. We also observe a dramatic halt in the expression of genes required for ribosome biogenesis and translation, as well as decrease in expression of diverse genes (cyclins, protein kinases) required for progression through the cell cycle. Only subsets of these changes were observed in a strain deleted for the TRK1 and TRK2 genes growing in the presence of sufficient potassium (50 mM). Research involving molecular genetics and metabolomic approaches aiming to clarify the primary targets for potassium requirements is currently ongoing. The effect of a sudden shortage of extracellular potassium was studied using a wt yeast strain. Samples of cell cultures grown in either, in the presence or in the absence of potassium, were taken after 10, 20, 40, 60 and 120 min of potassium shortage. We compared the expression profile of: 1) WT w/o K vs WT w/ KCl at 10 min: 2) WT w/o K vs WT w/ KCl at 20 min. 3) WT w/o K vs WT w/ KCl at 40 min. 4) WT w/o K vs WT w/ KCl at 60 min. 5) WT w/o K vs WT w/ KCl at 120 min. Two independent experiments were performed, except for the timepoint of 10 min. For each experiment a dye-swap was carried out. Chips analyzed: 2 for 10 min 4 for 20 min 4 for 40 min 4 for 60 min 4 for 120 min Total number of chips: 18

2012-10-13 | E-GEOD-24712 | biostudies-arrayexpress

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