AMPK activation exerts anti-senescence effect in human follicle dermal papilla cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE62798 | GEO | 2014/11/01
SECONDARY ACCESSION(S): PRJNA265181
REPOSITORIES: GEO
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Project description:We investigated the role of AMPK activation in the progression of senescence in HFDPCs. The anti-senescence effects of adenine, a recently identified AMPK activator, were determined in a comparison with AICAR, a pharmacological AMPK activator, in HFDPCs. The results showed that either adenine or AICAR induced phosphorylation of Thr172 of AMPK in HFDPCs. As revealed by microarray analysis, significant changes of gene expression pattern were observed in the high-passage HFDPCs compared with that at lower passage level. A chip study using total RNA recovered from three separate wild-type cultures of Human follicle dermal papilla cells (HFDPCs) and three separate cultures of a triple adenine-treated cells.
2014-11-01 | E-GEOD-62798 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for cell-based regenerative medicine in dentistry. PDLSCs inevitably acquire a senescent phenotype after prolonged in vitro expansion, and the key regulators of cells during replicative senescence remain unclear.</p><p><strong>METHODS:</strong> We cultured periodontal ligament stem cells to passages 4, 10 and 20 (P4, P10, P20). The senescent phenotypes, proliferation and migration ability of PDLSCs (P4, P10, P20) were detected, and non-targeted metabonomic sequencing was performed. We treated PDLSCs with AICAR and detected the expression of FOXO1, FOXO3a, FOXO6 and AMPK phosphorylation (p-AMPK) levels of replicating senescent PDLSCs to explore the correlation between the metabolic changes and the AMPK pathway.</p><p><strong>RESULTS:</strong> Immunofluorescence staining of γ-H2AX, β-galactosidase staining, cell scratch test and qPCR were performed to confirm the occurrence of replicative senescence in PDLSCs during passaging. Three groups of cells at passage 4 (P4), passage 10 (P10) and passage 20 (P20) were collected for non-targeted metabolomics analysis. Metabonomic sequencing showed that the metabolism of replicative senescence in PDLSCs varied significantly. In particular, the content of fatty acid metabolites decreased with senescence, including capric acid, stearic acid, myristic acid and dodecanoic acid. KEGG pathway analysis showed that the AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK and the profile of FOXO1 and FOXO3a, which are downstream of the AMPK signaling pathway, decreased with senescence. We treated PDLSCs with AICAR, an activator of the AMPK pathway, and the phosphorylated AMPK level at P20 PDLSCs was partially restored. </p><p><strong>CONCLUSION:</strong> In summary, our study suggests that the metabolic process of PDLSCs is active in the early stage of senescence, prefers to consume fatty acids, and is attenuated in the later stages of senescence. AMP accumulates in replicative senescent PDLSCs; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism. Our findings provide a new basis for the clinical application of periodontal ligament stem cells.</p>
2022-11-15 | MTBLS4568 | MetaboLights
Project description:AICAR is a metabolite with anti-tumoral properties. Its monophosphate derivative ZMP is an AMP mimetic activator of the protein kinases AMPK. However, AICAR also mediates AMPK-independent effects. A kinetic transcriptome analysis was therefore carried out in Ampkα1/α2 double knockout murine embryonic fibroblasts in response to AICAR in order to unveil these AMPK-independent functions,
2018-05-31 | GSE106460 | GEO
Project description:Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging associated frailty may preclude physical activity. AMP-activated protein kinase (AMPK) is a transcriptional regulator important for muscle physiology. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (2-month-old), aged (23-month-old) C57Bl/6 mice, and transgenic mice with muscle-specific mutated AMPK alpha-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3 to 14 days and tested in the Morris water maze, rotarod and open field. Improved water maze performance and motor function was observed, albeit at longer duration of administration, in aged (14 days AICAR) than young (3 days AICAR) mice. In the AMPKDN mice, the compound did not enhance behavior, providing support for a muscle mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus genes relevant to neuronal development and plasticity were enriched. Altogether, endurance related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions. Key words: Skeletal Muscle, Brain, Exercise, AMPK, Learning and Memory, Morris water maze 23-month old female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME) were housed under standard conditions, 3 mice per cage, with food and water ad libitum. Mice were injected intraperitoneally with 5-Aminoimidazole-4-carboxamide-1-a-D-ribofuranoside (AICAR, Toronto Research Chemicals Inc., Canada) dissolved in saline, 500 mg/kg/day for 3 (ACR3), 7 (ACR7) or 14 (ACR14) days or saline vehicle, for 3 (CTR) days. Thirty-three days after the final injection animals were deeply anesthetized with isofluorane and perfused transcardially with 0.9% NaCl solution. The gastrocnemius muscle and Hippocampus were quickly removed, frozen on dry ice and stored at M-bM-^HM-^R80 M-BM-0C for RNA isolation and microarray analysis.
2014-01-17 | E-GEOD-50873 | biostudies-arrayexpress
Project description:Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging associated frailty may preclude physical activity. AMP-activated protein kinase (AMPK) is a transcriptional regulator important for muscle physiology. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (2-month-old), aged (23-month-old) C57Bl/6 mice, and transgenic mice with muscle-specific mutated AMPK alpha-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3 to 14 days and tested in the Morris water maze, rotarod and open field. Improved water maze performance and motor function was observed, albeit at longer duration of administration, in aged (14 days AICAR) than young (3 days AICAR) mice. In the AMPKDN mice, the compound did not enhance behavior, providing support for a muscle mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus genes relevant to neuronal development and plasticity were enriched. Altogether, endurance related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions. Key words: Skeletal Muscle, Brain, Exercise, AMPK, Learning and Memory, Morris water maze
2014-01-17 | GSE50873 | GEO
Project description:Reversion from primed to naïve pluripotent status has been achieved by various signaling manipulation, but it is still unclear what signaling is the actual driving force to get over the hurdle from primed to naïve pluripotency. We previously reported that activation of AMP kinase (AMPK) contributed to maintenance of naïve pluripotency. Here, we further show that AMPK activators, AICAR, A769662 or metformin, can induce the reversion of primed mouse epiblast stem cells (mEpiSCs) to naïve pluripotent state. Primed mEpiSCs in our naïve cell culture condition with leukemia inhibitory factor (LIF) and 2 kinase inhibitors (2i) (2iL) never gave rise to naïve state cells. Addition of AICAR alone even in the absence of 2iL or either of AMPK inhibitors with LIF induced appearance of naïve-like cells from primed mEpiSCs. Through maintenance and passages of these cells in 2iL condition, clear naïve-like morphology colonies were purely obtained. They showed core naïve protein expression, and global naïve gene expression profiles. These cells contributed to chimeric mice including germline transmission. Inhibition of p38 signaling abolished the AMPK-elicited reversion and forced activation of p38 in primed mEpiSCs partially reproduced the naïve cell induction, suggesting that p38 is one of the critical downstream in AMPK activation. Single cell RNA-seq analysis under AICAR stimulation successfully demonstrated the reversion process with appearance of intermediate naïve-like population. AMPK pathway should be a novel critical driving force in reversion of primed to naïve pluripotency.
2021-07-21 | GSE175610 | GEO
Project description:To candidate phosphorylation sites of ORP8 in cells and the stoichiometric change of ORP8's phosphorylation when AMPK is activated,LC-MS/MS analysis of ORP8 immunoprecipitated from serum-starved cells and cells treated with AMPK activator AICAR was performed.
2023-10-24 | PXD036204 | Pride
Project description:Reversion from primed to naïve pluripotent status has been achieved by various signaling manipulation, but it is still unclear what signaling is the actual driving force to get over the hurdle from primed to naïve pluripotency. We previously reported that activation of AMP kinase (AMPK) contributed to maintenance of naïve pluripotency. Here, we further show that AMPK activators, AICAR, A769662 or metformin, can induce the reversion of primed mouse epiblast stem cells (mEpiSCs) to naïve pluripotent state. Primed mEpiSCs in our naïve cell culture condition with leukemia inhibitory factor (LIF) and 2 kinase inhibitors (2i) (2iL) never gave rise to naïve state cells. Addition of AICAR alone even in the absence of 2iL or either of AMPK inhibitors with LIF induced appearance of naïve-like cells from primed mEpiSCs. Through maintenance and passages of these cells in 2iL condition, clear naïve-like morphology colonies were purely obtained. They showed core naïve protein expression, and global naïve gene expression profiles. These cells contributed to chimeric mice including germline transmission. Inhibition of p38 signaling abolished the AMPK-elicited reversion and forced activation of p38 in primed mEpiSCs partially reproduced the naïve cell induction, suggesting that p38 is one of the critical downstream in AMPK activation. AMPK pathway should be a novel critical driving force in reversion of primed to naïve pluripotency.
2021-07-21 | GSE157087 | 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:Ribonucleoside AICAr, a precursor in purine synthesis and a known activator of AMPK, was shown to induce monocytic differentiation in AML cell lines by inducing pyrimidine depletion followed by activation of ATR/Chk1 pathway and cell cycle arrest. Here we report transcriptional changes induced by AICAr in the primary AML sample (FAB-M2, FLT3 negative, NPM1 negative) in which AICAr induced differentiation and accumulation of macrophage cells in vitro. RNA-seq transcriptome analysis of primary AML cells isolated from the bone marrow of a patient with de novo FAB-M2 AML. Mononuclear cells were isolated from the bone marrow sample by density gradient separation and grown in RPMI supplemented with 10% FBS, 2 mM L-glutamine, 50 U/ml penicillin, 50 μg/ml streptomycin and 50 ng/ml IL-3, IL-6, SCF and FLT3L. Cells were treated with AICAr (0.4 mM) for 24 h. Experiment was performed in biological triplicates and total RNA was isolated for transcriptome analysis using Illumina high throughput sequencing.
2020-11-01 | E-MTAB-9209 | biostudies-arrayexpress