AMPK-dependent gene expression profiles in response to small molecule AMPK activators
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ABSTRACT:
PROVIDER: PRJNA411853 | ENA |
REPOSITORIES: ENA
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Project description:AMP-activated protein kinase (AMPK) is a major regulator of cellular energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. AMPK elicits acute and diverse metabolic effects by directly phosphorylating various targets. AMPK activation also promotes metabolic reprogramming in longer term via effects on gene expression. The aim of this study is to elucidate molecular mechanism(s) by which AMPK activation modulates metabolic adaptation through its impact on gene regulation.
2019-03-04 | GSE104170 | 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: Not available
| S-EPMC3905731 | biostudies-literature
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:Here we describe three new small-molecule activators of BMP signaling found by high throughput screening of a library of ~600,000 small molecules. Using a cell-based luciferase assay in the BMP4-responsive human cervical carcinoma clonal cell line, C33A-2D2, we identified three compounds with similar chemotypes, each ventralized zebrafish embryos and stimulated increased expression of the Bmp target genes, bmp2b and szl. Because these compounds ventralize zebrafish embryos, we have termed them “ventromorphins.” As expected for a BMP pathway activator, they induce the differentiation of C2C12 myoblasts to osteoblasts. Affymetrix RNA analysis confirmed the differentiation results and showed that ventromorphin treatments elicits a genetic response similar to BMP-4 treatment. Unlike isoliquiritigenin (SJ000286273), a flavone that maximally activates the pathway after 24 hours of treatment, all three ventromorphins induced SMAD1/5/8 phosphorylation within 30 minutes of treatment and achieved peak activity at 30 minutes or 1 hour, indicating that their direct responses are consistent with activated BMP signaling.
2018-02-14 | GSE95248 | GEO
Project description:Faithful execution of developmental programs relies on the acquisition of unique cell identities from pluripotent progenitors, a process governed by combinatorial inputs from numerous signaling cascades that ultimately dictate lineage-specific transcriptional outputs. Despite growing evidence that metabolism is integrated with many molecular networks, how pathways that control energy homeostasis may affect cell fate decisions is largely unknown. Here, we show that AMPK, a central metabolic regulator, plays critical roles in lineage specification. Although AMPK-deficient embryonic stem cells (ESCs) were normal in the pluripotent state, these cells displayed profound defects upon differentiation, failing to generate chimeric embryos and preferentially adopting an ectodermal fate at the expense of the endoderm during embryoid body (EB) formation. AMPK-/- EBs exhibited reduced levels of Tfeb, a master transcriptional regulator of lysosomes, leading to diminished endolysosomal function. Remarkably, genetic loss of Tfeb also yielded endodermal defects, while AMPK-null ESCs over-expressing this transcription factor normalized their differential potential, revealing an intimate connection between Tfeb/lysosomes and germ layer specification. The compromised endolysosomal system resulting from AMPK or Tfeb inactivation blunted Wnt signaling, while up-regulating this pathway restored expression of endodermal markers. Collectively, these results uncover the AMPK pathway as a novel regulator of cell fate determination during differentiation. 2 WT and 2 AMPK DKO ESC lines were differentiated into embryoid bodies (EBs) for various lengths of time (2, 4, 8, and 12 days) in high and low glucose conditions. Both ESC and EB samples were profiled by mRNA-seq to examine how global gene expression changes associated with ESC differentiation are affected by AMPK deletion.
2016-03-09 | E-GEOD-77705 | biostudies-arrayexpress
Project description:Defining CBX7-dependent chromatin architecture with rapid small-molecule inhibition
| PRJNA432965 | ENA
Project description: Not available
| S-EPMC3005419 | biostudies-literature
Project description:The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status and is crucial for the adaptive response to limited energy availability. AMPK is implicated in the regulation of many cellular processes, including autophagy. However, the precise mechanisms by which AMPK controls these processes and the identities of relevant substrates are not fully understood. With a protein microarrays we identified Cyclin Y as novel AMPK substrate that is phosphorylated at S326 both in vitro and in cells. Phosphorylation of Cyclin Y at S326 promotes its interaction with the cyclin-dependent kinase 16 (CDK16), thereby stimulating its catalytic activity. When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. Moreover, Cyclin Y/CDK16 is necessary for efficient AMPK-dependent activation of autophagy. This functional interaction is mediated by AMPK phosphorylating S326 of Cyclin Y. Collectively, we define Cyclin Y/CDK16 as downstream effector of AMPK for inducing autophagy.
2020-02-17 | PXD009968 | Pride