AMPK related of circRNA expression in C57 male mice myocardium
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE278398 | GEO | 2025/01/08
REPOSITORIES: GEO
Similar Datasets
Project description:AMPK related of circRNA expression in C57 male mice myocardium
| PRJNA1167178 | ENA
Project description:CircRNAs have complex biological functions and are involved in the development of several cardiovascular diseases. The relationship between circRNAs and myocardial ischaemia-reperfusion injury (MIRI) is not yet clear. The aim of this study was to investigate the expression of circRNAs in rat plasma, to examine the differential expression profile of circRNAs in the plasma of MIRI rats, and to explore whether these circRNAs are potentially significant and have potential as novel markers for the diagnosis of MIRI and as therapeutic targets.
2022-12-15 | GSE220750 | GEO
Project description:The adenosine monophosphate-activated protein kinase (AMPK) complex is a key enzyme in regulating cellular energy homeostasis. This complex is well studied and it is known to function in many cellular pathways. However, the interactome of AMPK complex has not yet been systematically established, although protein-protein interaction is critically important for protein function and regulation. Here, we applied tandem-affinity purification coupled with mass spectrometry (TAP-MS) strategy to study the AMPK complex interactome to discover its new functions. We conducted TAP-MS for all the seven AMPK complex subunits. The control TAP-MS group in the dataset includes forty-six control TAP-MS results using non-related baits. HEK293T proteome profiling results were used as background controls in HCIPs analysis. With these analysis, we identified 145 high confident interacting proteins (HCIPs) of AMPK, which allowed us to build an interaction network of AMPK complex.
2020-01-09 | PXD015466 | Pride
Project description:Long non-coding RNAs (lncRNA) and circular RNAs (circRNA) that sponge miRNAs could indirectly regulate gene expression, contributing to certain biological processes. This study aimed to investigate the role of non-coding RNAs in the pathogenesis of myocardial ischemia reperfusion-injury (MIRI). MIRI in male C57B/6J mice was induced by left anterior descending coronary artery ligation occlusion for 30 min, and 4 h of reperfusion. RNA sequencing was performed to obtain the mRNA and non-coding RNA expression profiles of the MIRI and sham groups. Bioinformatic methods were used to analyze the co-expression RNAs, miRNA binding sites and competitive endogenous RNA (ceRNA) pairs. Differentially expressed RNAs were identified with a cutoff fold change > 2 and p < 0.05. A total of 64 mRNAs were upregulated and 98 mRNAs were downregulated, and 10 lncRNAs were upregulated and 10 lncRNAs were downregulated. All altered (p < 0.05) mRNAs were selected for gene ontology and pathway analysis. The AMP-activated protein kinase (AMPK) signaling pathway was enriched in the downregulated genes, and the activation of AMPK was confirmed by Western blotting. The lncRNA co-expression network and ceRNA network base on genes in AMPK signaling pathway were then constructed, revealing that ENSMUST00000147762.7 and TUCP_000184 might be key regulators in MIRI induced AMPK activation. The expression levels of AMPK signaling-related RNAs and those involved in the ceRNA network were validated using qRT-PCR. Overall, this study identified potential new targets on AMPK signaling in MIRI.
2024-04-01 | GSE240842 | GEO
Project description:Sonntag2012 - mTOR model - IRS dependent regulation of AMPK by insulin
TSC1-TSC2 complex has two states: 1)
active (TSC1_TSC2_pS1387), regulated by AMPK_pT172; 2) inactive
(TSC1_TSC2_pT1462) regulated by Akt_pT308. Particularly, mTORC1 is
inhibited by TSC1_TSC2 in active state. AMPK is activated at T172
by the species IRS1_p activated by the insulin receptor upon
insulin stimulation. Consequently, AMPK_pT172 is inhibited by
mTORC1_pS2448 indirectly by the p70-S6K-negative feedback loop.
This model is described in the article:
A modelling-experimental
approach reveals insulin receptor substrate (IRS)-dependent
regulation of adenosine monosphosphate-dependent kinase (AMPK)
by insulin.
Sonntag AG, Dalle Pezze P, Shanley
DP, Thedieck K.
FEBS J. 2012 Sep; 279(18):
3314-3328
Abstract:
Mammalian target of rapamycin (mTOR) kinase responds to
growth factors, nutrients and cellular energy status and is a
central controller of cellular growth. mTOR exists in two
multiprotein complexes that are embedded into a complex
signalling network. Adenosine monophosphate-dependent kinase
(AMPK) is activated by energy deprivation and shuts off
adenosine 5'-triphosphate (ATP)-consuming anabolic processes,
in part via the inactivation of mTORC1. Surprisingly, we
observed that AMPK not only responds to energy deprivation but
can also be activated by insulin, and is further induced in
mTORC1-deficient cells. We have recently modelled the mTOR
network, covering both mTOR complexes and their insulin and
nutrient inputs. In the present study we extended the network
by an AMPK module to generate the to date most comprehensive
data-driven dynamic AMPK-mTOR network model. In order to define
the intersection via which AMPK is activated by the insulin
network, we compared simulations for six different hypothetical
model structures to our observed AMPK dynamics. Hypotheses
ranking suggested that the most probable intersection between
insulin and AMPK was the insulin receptor substrate (IRS) and
that the effects of canonical IRS downstream cues on AMPK would
be mediated via an mTORC1-driven negative-feedback loop. We
tested these predictions experimentally in multiple set-ups,
where we inhibited or induced players along the insulin-mTORC1
signalling axis and observed AMPK induction or inhibition. We
confirmed the identified model and therefore report a novel
connection within the insulin-mTOR-AMPK network: we conclude
that AMPK is positively regulated by IRS and can be inhibited
via the negative-feedback loop.
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2024-09-02 | BIOMD0000000580 | BioModels
Project description:Chronic kidney disease (CKD) remains a tremendous and growing burden on the healthcare system and new therapies are needed to prevent or slow disease progression. Metabolic dysregulation and mitochondrial dysfunction are important features of acute and chronic tissue injury across species, and human genetics and preclinical data suggest that the master metabolic regulator 5'-adenosine monophosphate activated protein kinase (AMPK) may be an effective therapeutic target for CKD. Merck has recently disclosed a pan-AMPK activator MK-8722 which was shown to have beneficial effects on metabolic parameters in preclinical models. In this study we investigate the effects of MK-8722 in a progressive model of diabetic nephropathy to determine whether activation of AMPK would be of therapeutic benefit. We find that MK-8722 administration in a therapeutic paradigm is profoundly reno-protective. We provide evidence that the therapeutic effects may be mediated by modulation of renal mitochondrial quality control as well as by attenuating fibrotic and lipotoxic mechanisms in kidney cells. These data further validate the concept that targeting metabolic dysregulation in CKD could be a potential therapeutic approach.
2019-07-25 | GSE134804 | GEO
Project description:To explore the differences in the expression of circRNA in myocardial ischemia-reperfusion injury and the potential effects of these differences in circRNA. Methods 6 SPF male SD rats were randomly divided into two groups, including 3 in Myocardial ischemia reperfusion group and 3 threading without ligation in control group by ligating the left anteriors branch for 40 minutes and reperfusing for 2 hours to establish a model of myocardial ischemia reperfusion injury. The myocardial specimens from the infarct area were taken for high-throughput sequencing analysis to obtain differently expressed circRNA. After that, GO and KEGG analysis were performed to speculate on the biological functions and possible biological pathways involved. RT-qPCR was used to verify the sequencing results of differential circRNA, and bioinformatics analysis predicted that circRNA could combine with miRNA to construct a visual network diagram and their interaction. Results Analyzing of 13576 circRNAs detected in 6 rats from MIRI group and control group, A total of 132 circRNAs showed significant differential expression, of which 82 were up-regulated and 50 were down-regulated. The results of GO and KEGG analysis suggest that differential circRNA is closely related to myocardial ischemia reperfusion injury, and KEGG analysis suggests that differential circRNA is involved in calcium, AMPK, mTOR and adrenaline signal pathways. 4 circRNAs were extracted from the up-regulated circRNA for RT-qPCR verification, and the results of 2 were consistent with the high-throughput sequencing results. circRNA-miRNA interaction analysis shows that circRNA interacts with a variety of miRNAs. Conclusions The expression of circRNA in myocardial reperfusion injury rats is significantly different, which may be involved in the occurrence and development of myocardial ischemia-reperfusion injury through miRNA sponge action of circRNA.
2022-06-30 | GSE207093 | GEO
Project description:Pancreatic beta cells (β-cells) differentiate during fetal life, but only postnatally acquire the capacity for glucose-stimulated insulin secretion (GSIS). The molecular mechanisms driving this maturation of β-cell function remain incompletely understood. Here, we show that the control of cellular signaling in β-cells fundamentally switches from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5'-adenosine monophosphate-activated protein kinase (AMPK), and that this is critical for functional maturation. Moreover, AMPK is activated by the dietary transition taking place during weaning, and this in turn inhibits mTORC1 activity to drive the adult β-cell phenotype. While forcing constitutive mTORC1 signaling in adult β-cells relegates them to a functionally immature phenotype with characteristic transcriptional and metabolic profiles, engineering the switch from mTORC1 to AMPK signaling is sufficient to promote β-cell mitochondrial biogenesis, a shift to oxidative metabolism, and functional maturation. We also show that type 2 diabetes, a condition marked by both mitochondrial degeneration and dysregulated GSIS, is associated with a remarkable reversion of the normal AMPK-dependent adult β-cell signature to a more neonatal one characterized by mTORC1 activation. Manipulating the way in which cellular nutrient signaling pathways regulate β-cell metabolism may thus offer new targets to improve β-cell function in diabetes.
2019-06-06 | GSE132261 | GEO
Project description:To build a circRNA-miRNA-mRNA network in the condition of NPRA deletion in the heart, we used circRNA microArray analysis form Arraystar to examine the expression of circRNAs in NPRA-/- and NPRA+/+ myocardium tissues.
2019-11-22 | GSE140798 | GEO
Project description:<p>Energy stress depletes ATP and induces cell death. Here we identify an unexpected inhibitory role of energy stress on ferroptosis, a form of regulated cell death induced by iron-dependent lipid peroxidation. We found that ferroptotic cell death and lipid peroxidation can be inhibited by treatments that induce or mimic energy stress. Inactivation of AMP-activated protein kinase (AMPK), a sensor of cellular energy status, largely abolishes the protective effects of energy stress on ferroptosis in vitro and on ferroptosis-associated renal ischaemia-reperfusion injury in vivo. Cancer cells with high basal AMPK activation are resistant to ferroptosis and AMPK inactivation sensitizes these cells to ferroptosis. Functional and lipidomic analyses further link AMPK regulation of ferroptosis to AMPK-mediated phosphorylation of acetyl-CoA carboxylase and polyunsaturated fatty acid biosynthesis. Our study demonstrates that energy stress inhibits ferroptosis partly through AMPK and reveals an unexpected coupling between ferroptosis and AMPK-mediated energy-stress signalling.</p>
2023-01-31 | MTBLS1399 | MetaboLights