Danio rerio
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA238932 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:During aging, the loss of metabolic homeostasis drives a myriad of pathologies. A central regulator of cellular energy, the AMP-activated protein kinase (AMPK), orchestrates organismal metabolism. However, direct genetic manipulations of the AMPK complex in mice have, so far, produced detrimental phenotypes. Here, as an alternative approach, we alter energy homeostasis by manipulating the upstream nucleotide pool. Using the turquoise killifish, we mutate APRT, a key enzyme in AMP biosynthesis, and extend the lifespan of heterozygous males. Next, applying an integrated omics approach identify that metabolic functions are rejuvenated in old mutants, which also display a fasting-like metabolic profile and resistance to high-fat diet. On the cellular level, heterozygous cells exhibit enhanced nutrient sensitivity, reduced ATP levels, and AMPK ¬activation. Finally, lifelong intermittent fasting abolishes the longevity benefits. Our findings suggest that perturbing AMP biosynthesis may modulate vertebrate lifespan, and propose APRT as a promising target for promoting metabolic health.
2023-05-23 | GSE190757 | GEO
Project description:Recent evidence has suggested that fluoxetine, a serotonin-reuptake inhibitor and emerging environmental contaminant, can have non-targeted effects on metabolism in fish exposed to this waterborne pollutant. Using the highest, environmentally relevant, detectable level of fluoxetine (540 ng/L) we examined the impact of fluoxetine on the miRNA profile in the liver of zebrafish that were both fed and fasted for a period of 7 days. These results were further compared to the miRNA profile of zebrafish fasted and fed for 7 days, which were not exposed to fluoxetine. Results indicated that several miRNA that were involved with downregulating genes/pathways in response to fasting were also upregulated in fish exposed to fluoxetine, irrespective to fasting or feeding. These results suggest fluoxetine can have non-targeted effects on metabolic pathways mediated through miRNA expression. Furthermore, specific miRNA (dre-let-7d & dre-miR-140-5p) were found to target the catalytic subunit (AMPKa1 & AMPKa2, respectively) of AMP-Kinase, a master regulator of metabolism. Using predictive software and qPCR validation, combined with the expression profile of these two miRNA, we were able to establish a significant relationship between the expression of these specific miRNA to the downregulation of AMPKa subunit under the influence of 540 ng/L fluoxetine. Adult, female zebrafish were either fed or fasted for 7 days with and without the presense of 540 ng/L fluoxetine, and livers extracted and miRNA purified for miRNA microaary experiment.
2014-02-21 | E-GEOD-55229 | biostudies-arrayexpress
Project description:Recent evidence has suggested that fluoxetine, a serotonin-reuptake inhibitor and emerging environmental contaminant, can have non-targeted effects on metabolism in fish exposed to this waterborne pollutant. Using the highest, environmentally relevant, detectable level of fluoxetine (540 ng/L) we examined the impact of fluoxetine on the miRNA profile in the liver of zebrafish that were both fed and fasted for a period of 7 days. These results were further compared to the miRNA profile of zebrafish fasted and fed for 7 days, which were not exposed to fluoxetine. Results indicated that several miRNA that were involved with downregulating genes/pathways in response to fasting were also upregulated in fish exposed to fluoxetine, irrespective to fasting or feeding. These results suggest fluoxetine can have non-targeted effects on metabolic pathways mediated through miRNA expression. Furthermore, specific miRNA (dre-let-7d & dre-miR-140-5p) were found to target the catalytic subunit (AMPKa1 & AMPKa2, respectively) of AMP-Kinase, a master regulator of metabolism. Using predictive software and qPCR validation, combined with the expression profile of these two miRNA, we were able to establish a significant relationship between the expression of these specific miRNA to the downregulation of AMPKa subunit under the influence of 540 ng/L fluoxetine.
2014-02-21 | GSE55229 | GEO
Project description:Danio rerio larvae exposed to SSRIs Fluoxetine and Sertraline
| PRJNA145459 | ENA
Project description:Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 µg/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip® Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek® Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 µg/L and 131 at 250 µg/L; and after sertraline exposure was 33 at 25 µg/L and 52 at 250 µg/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish. Zebrafish (Danio rerio) were obtained from the Zebrafish Research Facility maintained at the Center for Environmental Biotechnology at the University of Tennessee. Fish husbandry, spawning, and experimental procedures were conducted with approval from the UT Insititutional Animal Care and Use Committee (Protocol #1690-1007). Water for holding fish and conducting experiments (hereafter referred to as fish water) consisted of MilliQ water (Millipore, Bedford, MA) with ions added: 19 mg/L NaHCO3, 1 mg/L sea salt (Instant Ocean Synthetic Sea Salt, Mentor, OH), 10 mg/L CaSO4, 10 mg/L MgSO4, 2 mg/L KCl. Embroyos were obtained by spawning adult fish with no history of contaminant exposure. Fertilization of embryos took place at the same time (<15 minutes), such that larvae used in experiments were of similar age at the time of exposure. All activities (maintenance of adult fish, spawning, and experiments) were conducted in an environmental chamber with a temperature of 27 +/- 1 C and 14:10h light:dark photoperiod. Larval zebrafish (72 hpf) were exposed for 96 h in 200ml fish water containing appropirate amount of SSRI stock (i.e. fluoxetine or sertraline). There were four SSRIs treatments (25 and 250 ug/L fluoxetine and 25 and 250 ug/L sertraline) and one control (no SSRIs) with triplicate beakers and each beaker contained about 100 larval fish. During exposure for 96 hours, beakers were kept covered to prevent water evaporation and fish were not fed (i.e., fish consumed their yolk sac).
2012-09-06 | E-GEOD-31712 | biostudies-arrayexpress
Project description:The serine/threonine kinase LKB1 is a tumor suppressor gene which also plays key roles in metabolic function in peripheral tissues through its direct phosphorylation and activation of the AMP-activated protein kinase (AMPK). The LKB1/AMPK pathway plays key roles in the liver in suppressing transcriptional programs of gluconeogenesis and lipogenesis, and hepatic LKB1 is required for the ability of the type 2 diabetes agent metformin to lower blood glucose levels in mice. To more broadly define how the LKB1/AMPK pathway controls hepatic metabolism, transcriptional profiling was employed using mice with an inducible liver-specific deletion of Lkb1. Unexpectedly, LKB1/AMPK signaling broadly controls the expression of many phase I xenobiotic metabolism genes, including several members of the cytochrome P450 family. In particular, expression of CYP2E1, an important mediator of drug detoxification, was markedly reduced upon LKB1 loss. LKB1 liver-specific knockout mice exposed to hepatocarcinogens, exhibited marked resistance to carcinogen-induced hepatocyte apoptosis, proliferation, senescence, and liver fibrosis and tumorigenesis.
2019-05-01 | GSE21984 | GEO
Project description:Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 µg/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip® Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek® Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 µg/L and 131 at 250 µg/L; and after sertraline exposure was 33 at 25 µg/L and 52 at 250 µg/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish.
2012-09-06 | GSE31712 | GEO
Project description:We show activation of AMP kinase (AMPK) with single chemical compounds can endow naïve pluripotency. AMPK activators reverted early-stage differentiating cells or epi-stem cells to naïve state. Moreover, AMPK activators reverted human ESCs to naïve state with pluripotent gene expression profiles and X-chromosome reactivation.
2019-03-30 | GSE92725 | GEO
Project description:We show activation of AMP kinase (AMPK) with single chemical compounds can endow naïve pluripotency. AMPK activators reverted early-stage differentiating cells or epi-stem cells to naïve state. Moreover, AMPK activators reverted human ESCs to naïve state with pluripotent gene expression profiles and X-chromosome reactivation.
2019-03-30 | GSE92441 | GEO
Project description:To explore the function of AMPK signaling in acute myeloid leukemia (AML), we used shRNA to knock down the expression of PRKAA1, the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK), in primary human AML cells and performed RNA-seq experiment to profile transcriptional changes upon AMPK inactivation.
2018-06-01 | GSE114105 | GEO