E-PROT-91
Ontology highlight
ABSTRACT:
PROVIDER: E-PROT-91 | ExpressionAtlas | 2022-01-10
REPOSITORIES: ExpressionAtlas
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Project description:Heart performance declines with age. Reduced protein quality control (PQC) due to decreased function of the ubiquitin/proteasome system (UPS), autophagy, and/or chaperone-mediated protein refolding is a likely contributor to age-associated cardiac performance decline. The transcription factor FOXO participates in the regulation of genes involved PQC and a host of other processes. Here, the effect of cardiac-restricted dFOXO overexpression was investigated in Drosophila, a genetically pliable and rapidly aging model. Modest dFOXO overexpression in the heart was protective, ameliorating functional decline with age. Increased expression of genes associated predominantly with UPS relative to other PQC components accompanied dFOXO-mediated cardioprotection, which was corroborated by a significant decrease in ubiquitinated myocardial proteins. In agreement, knockdown of upregulated UPS components seemingly induced premature aging. Despite these findings, excessive dFOXO overexpression or knockdown proved detrimental to heart function and overall organismal development. This study highlights Drosophila as a model of cardiac aging and FOXO as a tightly-regulated mediator of proteostasis and heart performance over time. Two replicates of 4 different samples were analyzed. Two of these samples were controls (GMH5 x yw 1 week and GMH5 x yw 5 week).
2016-07-01 | E-GEOD-73205 | biostudies-arrayexpress
Project description:To identify the gene regulatory network during heart aging, we used the RNA-seq to analyze the gene expression profile difference between adult mouse heart and aging mouse heart.
2023-05-04 | GSE202373 | GEO
Project description:The role of p53 in assuring longevity through prevention of cancer is well established, but how it specifically regulates aging is still controversial. Our assumption is that distinct p53-pathways regulate tumor suppression and aging and that p66Shc is one of the master regulators of the p53 aging function. p66Shc longevity determinant protein acts as a downstream target of p53 and it is indispensable for the ability of activated p53 to induce elevation of intracellular oxidants and apoptosis. We used microarray to gain insight into the mechanism of the physiological activation of p53-p66Shc pathway Total RNA was extracted from freshly isolated thymus, liver, heart and lung of two months old mice (pool of four mice for each genotype)
2012-04-01 | E-GEOD-28417 | biostudies-arrayexpress
Project description:Heart performance declines with age. Reduced protein quality control (PQC) due to decreased function of the ubiquitin/proteasome system (UPS), autophagy, and/or chaperone-mediated protein refolding is a likely contributor to age-associated cardiac performance decline. The transcription factor FOXO participates in the regulation of genes involved PQC and a host of other processes. Here, the effect of cardiac-restricted dFOXO overexpression was investigated in Drosophila, a genetically pliable and rapidly aging model. Modest dFOXO overexpression in the heart was protective, ameliorating functional decline with age. Increased expression of genes associated predominantly with UPS relative to other PQC components accompanied dFOXO-mediated cardioprotection, which was corroborated by a significant decrease in ubiquitinated myocardial proteins. In agreement, knockdown of upregulated UPS components seemingly induced premature aging. Despite these findings, excessive dFOXO overexpression or knockdown proved detrimental to heart function and overall organismal development. This study highlights Drosophila as a model of cardiac aging and FOXO as a tightly-regulated mediator of proteostasis and heart performance over time.
2016-07-01 | GSE73205 | GEO
Project description:Impaired mitochondrial function has been implicated in the pathogenesis of type 2 diabetes, heart failure and neurodegeneration as well as during aging. Studies with the PGC-1 transcriptional coactivators have demonstrated that these factors are key components of the regulatory network that controls mitochondrial function in mammalian cells. Here we describe a genome-wide coactivation assay to globally identify the transcriptional partners for PGC-1α. These analyses revealed a molecular signature of the PGC-1α transcriptional network, and identified BAF60a (Smarcd1), a subunit of the SWI/SNF chromatin-remodeling complex, as a critical regulator of lipid homeostasis. Adenoviral-mediated expression of BAF60a stimulates fatty acid β-oxidation in cultured hepatocytes and reduces hepatic triglyceride levels in diet-induced obese mice. BAF60a physically interacts with PGC-1α and is recruited to PPARα target genes in the fasted liver. Liver-specific RNAi knockdown of BAF60a impairs fatty acid oxidation and results in severe hepatic steatosis following starvation. These results define a role for the SWI/SNF complexes in the regulation of hepatic lipid metabolism, and reveal a potential target for therapeutic intervention. Experiment Overall Design: Primary hepatocytes were isolated from C57/Bl6J mice (10 weeks old) and transduced with recombinant adenoviruses expressing GFP or BAF60a for 40 hrs. Total RNA was isolated for array analysis.
2008-10-20 | E-GEOD-9523 | biostudies-arrayexpress
Project description:The endogenous peptide Apelin is crucial for maintaining heart function in pressure overload and aging Experiment Overall Design: Heart samples from Apelin knockout mice with pressure overload and sham control together with the wild-type mice with pressure overload and sham were compared
2008-06-15 | E-GEOD-7781 | biostudies-arrayexpress
Project description:RREB1 Regulates Neuronal Proteostasis and Microtubule Network Function
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Project description:Myc, a member of the Myc Network, supervises proliferation, metabolism and ribosomal function. The Mlx Network cross-talks with the Myc Network and regulates overlapping functions. We describe here the consequences of conditional Myc and/or Mlx gene knockouts (KOs) in primary and immortalized murine embryonic fibroblasts (MEFs). MycKO and MycKOxMlxKO “double KO” (DKO) primary MEFs, but not MlxKO MEFs, rapidly growth-arrested and displayed features of aging and senescence. In DKO MEFs, these were transient, indicating that Mlx was necessary to maintain them. KO MEFs deregulated transcripts pertaining to mitochondrial and ribosomal structure and function, cell cycle, aging, senescence and DNA damage. The expression of DNA damage-related proteins was also abnormal. Immortalized KO MEFs remained proliferation-competent but demonstrated differential sensitivities to genotoxic agents. Immortalized MycKO MEFs spontaneously developed tetraploidy that was Mlx-dependent. Different aspects of MEF aging, senescence and DNA damage responses are therefore differentially regulated by the Myc and Mlx Networks.
2023-08-28 | GSE210362 | GEO
Project description:VEGF family members are important regulators of vascular functions. Promoting VEGFA signalling in aged mice has been shown to delay various aging phenotypes and extend the survival of aged mice. Although there is profound knowledge on functions of VEGFA, VEGFB has not been investigated in the context of cardiac aging. Our RNA data of aged mouse hearts revealed significant downregulation of Vegfb in the heart, specifically in endothelial cells and cardiomyocytes, while VEGFB expression was reduced in endothelial cells, fibroblasts and cardiomyocytes in aged human hearts. By contrast, VEGFB expression was exclusively reduced in cardiomyocytes of patients with cardiac hypertrophy. Hence, we investigated whether Vegfb gene therapy can revert age-dependent cardiac pathologies. We overexpressed Vegfb186, the soluble VEGFB isoform, via AAV9 vector transduction into 18-month-old C57Bl/6J male mice. AAV9-Vegfb treatment prevented progression age-related diastolic dysfunction and decreased cardiac fibrosis. We further found a rescue of aging-related left ventricular denervation in the hearts of AVV9-Vegfb treated old mice which was associated with an increase in heart rate variability. However, heart to body weight ratio and cardiomyocyte hypertrophy were increased in the AAV9-Vegfb treated mouse hearts, without alteration of cardiac systolic or diastolic function. Histological and transcriptomic analyses revealed that VEGFB186 induces compensatory cardiac hypertrophy which was accompanied by a rescued length-width-ratio, reduced fibrosis and the absence of cardiac inflammation. Cardiac single-nuclei RNA sequencing further suggested that AAV9-Vegfb treatment affects cardiac hypertrophy putatively via STAT3 which was validated in vitro. In conclusion, our data reveals that Vegfb overexpression partially reverses pathological alterations in the aging heart. Despite the overall improvement of the age-related cardiac phenotype, the AAV9-Vegfb-mediated induced cardiac hypertrophy which might reflect protective hypertrophy.
2024-11-30 | E-MTAB-14595 | biostudies-arrayexpress
Project description:The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration. In order to monitor the whole regeneration process, we recovered samples at different time points post-injury: 4 h, 1 day, 3 days, 7 days, 14 days and 90 days (respectively 4 hpi, 1 dpi, 3 dpi, 7 dpi, 14 dpi and 90 dpi). Cryoinjured hearts were compared to healthy hearts from control fish in 3 independent experiments.
2016-06-01 | E-GEOD-67665 | biostudies-arrayexpress