E-GEOD-50118
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA216106
PROVIDER: E-GEOD-50118 | ExpressionAtlas | 2015-07-27
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Effect of AMPK activation by AICAR on MA-10 Leydig cell transcriptome
| PRJNA216106 | ENA
Project description:To investigate the functions of AMPK activation on maturation of hiPSC derived cardiomyocytes, we treated 3D hiPSC derived cardiomyocytes with AMPK activator EX229 at 10 µM for 7 days. Transcriptomic analyse was performed to identify molecular actions of AMPK activation.
2022-05-27 | GSE203480 | GEO
Project description:5’-AMP-Activated Protein Kinase (Ampk) is an energy gatekeeper that responds to decreases in available ATP by inhibiting energy-consuming processes like protein synthesis and promoting energy-generating processes like glucose uptake. Recently, our lab showed that Lkb1, a previously unstudied kinase in B cell immunology and the main upstream kinase of Ampk, had a critical and unexpected role in B cell activation and germinal center formation. In T cells knockout of the downstream target Ampk, only partially phenocopies Lkb1 deletion, so we sought to determine whether the role of Lkb1 in B cells depends on Ampk. We find Ampk is activated upon B cell stimulation in vitro. Surprisingly, however, Ampk activation occurs in the absence of energetic stress, and B cells continue to grow and divide despite Ampk activity. We performed an IP-MS substrate screen to identify Ampk targets and only identified a limited repertoire of canonical targets, and many non-canonical targets. Despite activation of Ampk and the major role of Lkb1 in B cell activation, B cell specific deletion of Ampk does not significantly affect B cell activation, differentiation, carbon handling, gene expression, or humoral immune responses. The only major effect of Ampk loss was accelerated downregulation of IgD during stimulation, which was preceded by downregulation of the IgD regulator Zfp318. Early activation of Ampk by pharmacological means also has little impact on B cell function, although treatment with the biguanide Phenformin critically impairs germinal center formation and class switch recombination in vivo, but does not significantly impair antigen-specific antibody responses. Combined, our results suggest an unexpected and unexplained activation of Ampk in B cells.
2019-06-16 | GSE121025 | GEO
Project description:Background & Aims: Other than hepatitis B or C virus infection, Hepatitis E virus (HEV) infection is generally asymptomatic or leads to acute and self-limiting hepatitis. However, the mechanism of host cell defense against HEV is unclear. Viruses are known to perturb host cellular metabolism to enable their replication and spread. AMP-activated protein kinase (AMPK) activation is crucial for the regulation of cell homeostasis. We thus investigated the role of AMPK in HEV infection. Methods: Huh7, THP1 and HepG2 cells inoculated with infectious HEV viral particle or Huh7 and organoids transfected with in vitro generated subgenomic or full-length GT3 (Kernow-C1 p6 strain) HEV RNA, namely, p6Luc or p6 were used to model HEV infection. Viral replication and genes expression were quantified. Activation of AMPK, innate immune response and autophagy process were assessed. Results: We found HEV infection can trigger AMPK activation by phosphorylation of AMPK at threonine 172 by transfecting HEV viral RNA into host cells or inoculating host cells with infectious HEV viral particle. The activation of AMPK is associated with HEV induced mitochondrial damage and ATP deficiency. Pharmacological activation of AMPK using 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) attenuated HEV replication, which was reversed by an AMPK inhibitor (compound C). Lentivirus-mediated knockdown of AMPK provided further evidence that AMPK has an antiviral effect on HEV replication. These results suggested that AMPK activation is a potent strategy of host cells for HEV clearance. Consistent with its antiviral effect, AMPK activation potentiated the expression of genes with antiviral properties (e.g., IFNs, ISG15, and IRF9) and inhibited inflammatory response (e.g., NF-KB NLRP3 and IL-1β). Meanwhile, HEV and activated AMPK also decreased autophagosome accumulation by decreasing induction of autophagy and autophagic degradation. Consistently, we found inhibition of AMPK efficiently augmented HEV induced autophagosome accumulation, evidenced by a marked increase in LC3II. Our previous study showed that rapamycin, an activator of autophagic induction by inhibiting mTOR, and Bafilomycin A1, an inhibitor of autophagic degradation, has a potent pro-HEV effect under AICAR treatment. Moreover, Wortmannin inhibiting autophagic induction recover AMPK inhibitor induced HEV replication. Together, these results suggested that HEV induced AMPK activation can serve to protect HEV infected cells from HEV infection by attenuating autophagosome and promoting innate immunity. Conclusions: Here we show that HEV infection can activate AMPK phosphorylation, which attenuates autophagosome accumulation and increases innate immune signaling. Thus, the AMPK activation in response to HEV infection is critical in host cells for rapid viral clearance by coordinating autophagic process and establishing persistent antiviral immunity.
2024-03-31 | GSE262469 | GEO
Project description:Emerging evidence indicates that metabolic dysregulation drives prostate cancer (PCa) progression and metastasis. AMPK is a master regulator of metabolism although its role in PCa remains unclear. Here we show that genetic and pharmacological activation of AMPK provides a dramatic protective effect on PCa progression in vivo. We show that AMPK activation induces PGC1-alpha expression leading to a catabolic metabolic reprogramming of PCa cells. This catabolic state is characterised by increased mitochondrial gene expression, increased fatty acid oxidation, decreased lipogenic potential, decreased cell proliferation and decreased cell invasiveness. Together, these changes inhibit PCa disease progression. Additionally, we identify a gene network involved in cell cycle regulation that is inhibited by AMPK activation. Strikingly, we show a strong correlation between this gene network and PGC1-alpha gene expression in human PCa. Taken together our findings strongly support the use of AMPK activators for clinical treatment of PCa to improve patient outcome.
2023-03-29 | PXD040731 | Pride
Project description:Emerging evidence indicates that metabolic dysregulation drives prostate cancer (PCa) progression and metastasis. AMPK is a master regulator of metabolism although its role in PCa remains unclear. Here we show that genetic and pharmacological activation of AMPK provides a dramatic protective effect on PCa progression in vivo. We show that AMPK activation induces PGC1a expression leading to a catabolic metabolic reprogramming of PCa cells. This catabolic state is characterised by increased mitochondrial gene expression, increased fatty acid oxidation, decreased lipogenic potential, decreased cell proliferation and decreased cell invasiveness. Together, these changes inhibit PCa disease progression. Additionally, we identify a gene network that is inhibited by AMPK activation involved in cell cycle regulation. We show correlation between this gene network and PGC1a expression in human PCa. Taken together our findings strongly support the use of AMPK activators for clinical treatment of PCa.
2023-10-26 | GSE214601 | GEO
Project description:Background: We previously reported that intake of a water-soluble extract of Pacific Krill (WEPAK) by mice decreases triglyceride accumulation in liver and suppresses weight gain induced by a high-fat diet. However, the mechanisms mediating these phenomena were not investigated or revealed in our previous study. Methods and Findings: Here, we investigated the effect of WEPAK in mouse liver using transcriptome analysis and discovered that WEPAK induced the expression of genes categorized into the gene ontology (GO) term lipid metabolic process. Furthermore, two regulators of fatty acid β-oxidation, AMPK and PPARδ, were induced in the liver and muscle of mice that had taken in WEPAK. Conclusions: These results indicate that WEPAK increased the expression of genes related to fatty acid β-oxidation via activation of AMPK and PPARδ. WEPAK may have the effect of improving lipid metabolism and, therefore, may be beneficial in the prevention of obesity. Examination of 4 different feeding condtion (4mice/group)
2013-04-22 | E-GEOD-37379 | biostudies-arrayexpress
Project description:Lee and colleagues demonstrate that sustained activation of AMPK enhances differentiation of iPSC-derived cardiomyocytes. Sustained AMPK activation decreased histone acetylation at known target sites for nuclear-localized sirtuins, suggesting that AMPK activation enhances sirtuin activity. AMPK-induced sirtuin-mediated deacetylation of histone proteins may regulate chromatin accessibility and enhance cardiomyocyte differentiation.
2020-06-12 | GSE152265 | GEO
Project description:Physical activity promotes metabolic and cardiovascular health benefits that derive in part from the transcriptional responses to exercise that occur within skeletal muscle and other organs. There is interest in discovering a pharmacologic exercise mimetic that could imbue wellness and alleviate disease burden. However, the molecular physiology by which exercise signals the transcriptional response is highly complex, making it challenging to identify a single target for pharmacological mimicry. The current studies evaluated the transcriptome responses in skeletal muscle, heart, liver, and white and brown adipose to novel small molecule activators of AMPK (pan-activators for all AMPK isoforms) compared to that of exercise. A striking level of congruence between exercise and pharmacological AMPK activation was observed across the induced transcriptome of these five tissues. However, differences in acute metabolic response between exercise and pharmacologic AMPK activation were observed, notably for acute glycogen balances and related to the energy expenditure induced by exercise but not pharmacologic AMPK activation. Nevertheless, intervention with repeated daily administration of short-acting activation of AMPK was found to mitigate hyperglycemia and hyperinsulinemia in four rodent models of metabolic disease and without the cardiac glycogen accretion noted with sustained pharmacologic AMPK activation. These findings affirm that activation of AMPK is a key node governing exercise mediated transcription and is an attractive target as an exercise mimetic.
2019-02-27 | GSE92719 | GEO
Project description:Chronic Activation of γ2 AMPK Induces Obesity and Reduces Beta Cell Function
| PRJNA296960 | ENA