Ketogenic diet induces p53-dependent cell senescence in multiple organs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA978062 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24781033_1.fastq.gz | Fastqsanger.gz | |||
| SRR24781033_2.fastq.gz | Fastqsanger.gz | |||
| SRR24781034_1.fastq.gz | Fastqsanger.gz | |||
| SRR24781034_2.fastq.gz | Fastqsanger.gz | |||
| SRR24781035_1.fastq.gz | Fastqsanger.gz |
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Project description:Mice on two different ketogenic diets induce p53 and cellular senescence in multiple organs, including heart and kidney. This is mediated through inactivation of MDM2 by caspase-2 cleavage, leading to p53 accumulation and induction of p21. Ketogenic diet also induced pAMPK, suggesting that persistent activation leads to p53-dependent senescence.
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Project description:Analysis of liver gene transcription during feeding of a ketogenic diet. Ketogenic diets may alter physiologic and metabolic profiles in a direction that favors weight loss. C57BL/6J mice were maintained for six weeks on either chow or ketogenic diet. Mice eating KD had lower weights, 90% reduction in insulin levels and increased energy expenditure compared to animals fed chow. Despite consumpiton of a very high fat diet serum lipids remained normal. Here we show that consumption of KD shifted liver metabolism to drastically increased fatty acid oxidation. Concurrently, expression of genes involved in fatty acid synthesis were markedly suppressed. Keywords: Hepatic profile
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Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed. Two-condition experiment, Normal diet-fed rat brain vs. Ketogenic diet-fed rat brain. Duplicate per array
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Project description:Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks Keywords: RNA Expression Array Hearts from 12 week-old mice that were maintained on a standard polysacchardide-rich chow until the age of 8 weeks, at which time they were switched to a ketogenic diet (ad libitum) and maintained for 4 additional weeks prior to collection of tissues
2010-06-16 | E-GEOD-21368 | biostudies-arrayexpress
Project description:The downstream events and target genes of p53 in senescence responses are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, a key player in mediating T cell inhibitory function, in p53-mediated cellular senescence. Overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistently, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued Foxp3 expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through p21 induction and subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression and ROS production and is necessary for p53-mediated senescence. control and treated samples (human), young passage (p3) or old passage (p7) samples (mouse)
2015-08-13 | E-GEOD-71980 | biostudies-arrayexpress
Project description:As a critical cellular stress sensor, p53 mediates a variety of defensive processes including cell-cycle arrest, apoptosis, and senescence to prevent propagation of hyperproliferative cells or cells with a damaged genome, hence the formation of neoplasia. Transactivation of downstream genes plays an important while sometimes controversial role in regulating these cellular processes. To evaluate the dependence on transcriptional activation in p53’s activities, we generated genetically-modified mouse lines carrying mutations in the transactivation domains (TADs) of p53. These transactivatio-deficient mutants serve as unique reagents to probe the dependence on robust transactivation in p53-mediated cellular functions, as well as the underneath mechanisms. To identify genes differentially regulated by these p53 mutants, we performed gene expression profiling analysis on mouse embryonic fibroblast cells (MEFs) from these mice in the context of oncogenic Ras-induced premature cellular senescence. Mouse embryonic fibroblasts (MEFs) with different p53 genotypes were infected with retroviral H-Ras V12, which induces premature cellular senescence in p53 wild-type MEFs but not in p53 null MEFs. 5 genotypic groups of MEFs were used in the study: (i) p53L25Q/W26S, or "25,26", in which the first TAD (transactivation domain) of p53 is disrupted by the mutation, 5 biological samples; (ii) p53W53Q/F54S, or "53,54", in which the second TAD of p53 is disrupted by the mutation, 3 biological samples; (iii) p53L25Q/W26S/W53Q/F54S, or "QM", in which both TADs or p53 are disrupted, 3 biological samples; (iv) p53 wild-type, or "WT", 6 biological samples; (v) p53 null, or "Null", 6 biological samples.
2011-05-13 | E-GEOD-27901 | biostudies-arrayexpress
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed.
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Project description:Rationale: Sepsis patients suffer from severe metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutritional regimes. We therefore hypothesize that a ketogenic diet improves sepsis treatment. Objectives: We investigated the safety and feasibility of a ketogenic diet in sepsis patients. Methods: We conducted a monocentric open-labeled randomized controlled trial (DRKS00017710) enrolling adult sepsis patients randomly assigned to either ketogenic or standard high-carbohydrate diet for 14 days with follow-up until day 30. The primary outcome measure was β-hydroxybutyrate serum concentration on day 14. Secondary outcomes included safety, clinical and immunological changes. Measurements and Main Results: 40 critically ill septic patients were assigned to the study groups. Increase in β-hydroxybutyrate concentrations from baseline to day 14 was markedly greater under ketogenic diet (1.2 ±0.9) compared to controls (-0.3 ±0.4); estimated mean difference 1.4 (95%-CI 1.0-1.8; p<0.0001). During ketogenic diet, no patient required insulin treatment beyond day 4, whereas 35% to 60% of control patients did (p=0.0095). Metabolic side effects were not observed under ketogenic diet. Ventilation-free (IRR 1.7; 95%-CI: 1.5 to 2.1; p<0.0001), vasopressor-free (IRR 1.7; 95%-CI: 1.5 to 2.0; p<0.0001), dialysis-free (IRR 1.5; 95%-CI: 1.3 to 1.8; p<0.0001), and ICU-free days (IRR 1.7; 95%-CI: 1.4 to 2.1; p<0.0001) significantly increased in patients under ketogenic diet. There was no difference in 30-day mortality. Analyses indicated favorable changes towards immune homeostasis. Conclusions: Ketogenic diet is a feasible and safe nutritional regimen in septic patients promoting recovery from sepsis-related organ dysfunction and could become a new tool in modern treatment concepts.
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Project description:Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks Keywords: RNA Expression Array
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Project description:The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression and ROS production and is necessary for p53-mediated senescence.
2015-08-13 | GSE71980 | GEO