POLB regulates proliferation and apoptosis of bovine primary myocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Bos taurus
PROVIDER: GSE262289 | GEO | 2024/03/29
REPOSITORIES: GEO
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Project description:Transgenic mice with cardiac-restricted overexpression of connective tissue growth factor (CTGF) have substantially increased tolerance towards ischemia/reperfusion injury. In the transgenic mouse model, we found that CTGF induces expression of severeal genes putatively involved in cardioprotection. The purpose of this study was to determine gene expression in cardiac myocytes stimulated with purified, recombinant CTGF, comparing unstimulated and stimulated samples. The cytoprotective actions of CTGF was recflected in the transcriptome of CTGF-stimulated cardiac myocytes. Gene ontology analysis revealed that genes included under the terms anti-apoptosis, response to wounding, and response to stress were significantly overrepresented in cardiac myocytes exposed to CTGF. Serveral of the most higly up-regulated genes have previously been reported to exert cardioprotective actions and increase tolerance towards ischemia/reperfusion injury. Primary, adult cardiac myocytes were cultured in the absence (n=6) or presence (n=6) of 200 nmol/L recombinant CTGF for 48 hours.
2015-02-01 | E-GEOD-36073 | biostudies-arrayexpress
Project description:Transgenic mice with cardiac-restricted overexpression of connective tissue growth factor (CTGF) have substantially increased tolerance towards ischemia/reperfusion injury. In the transgenic mouse model, we found that CTGF induces expression of severeal genes putatively involved in cardioprotection. The purpose of this study was to determine gene expression in cardiac myocytes stimulated with purified, recombinant CTGF, comparing unstimulated and stimulated samples. The cytoprotective actions of CTGF was recflected in the transcriptome of CTGF-stimulated cardiac myocytes. Gene ontology analysis revealed that genes included under the terms anti-apoptosis, response to wounding, and response to stress were significantly overrepresented in cardiac myocytes exposed to CTGF. Serveral of the most higly up-regulated genes have previously been reported to exert cardioprotective actions and increase tolerance towards ischemia/reperfusion injury.
2015-02-01 | GSE36073 | GEO
Project description:Title: Regulation of gene expression through mitogen-activated protein kinase cascades in cardiac myocytes.<br/> Description: The aim of this study is to identify the changes in gene expression induced in rat neonatal <br/> ventricular myocytes, a well-established cell culture model, by endothelin-1, <br/> a known hypertrophic agonist, and to determine which of the changes are <br/> mediated through the ERK cascade. This continues TKAC^Ys previous study of the <br/> effects of oxidative stress, which induces cardiac myocyte apoptosis.<br/>
2006-10-01 | E-MIMR-3 | biostudies-arrayexpress
Project description:The decline of cognitive function is a feature of normal human aging and is exacerbated in AlzheimerM-bM-^@M-^Ys disease (AD). DNA repair declines in brain cells during normal aging and even more so in AD. Here we show that experimental reduction in levels of the base excision repair enzyme, DNA polymerase M-NM-2 (Polb) renders neurons vulnerable to age-related dysfunction and degeneration in a mouse model of AD. Whereas 3xTgAD mice exhibit age-related extracellular amyloid b-peptide (Ab) accumulation and cognitive deficits, but no neuronal death, 3xTg/Polb+/- mice accumulates intracellular Ab and neurons die in the hippocampus and cerebral cortex. The DNA repair-deficient 3xTgAD mice exhibited increased DNA strand breaks and apoptotic caspase activation with loss of hippocampal volume, and impaired synaptic plasticity and memory retention. Molecular profiling revealed remarkable similarities in gene expression alterations in brain cells of AD patients and 3xTgAD/Polb+/- mice including multiple abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in oxidative DNA damage processing is sufficient to render neurons vulnerable to AD-related pathogenic molecular and cellular alterations that result in the dysfunction and death of neurons, and associated cognitive deficits. 4 mouse strains were used in these experiments, the 3xTgAD and Pol M-NM-2 (+/-) mice were bred at the National Institute on Aging (Baltimore, Maryland). The original line 3xTgAD line was generated as described previously (Oddo, et. al 2003) and possess APPswe, PS1M146V, and tauP301L mutations. DNA polymerase beta heterozygous mice, Pol M-NM-2 (+/-), were crossed with the 3xTgAD mice to generate a 3xTgAD/Pol M-NM-2 (+/-) mouse. The Wt strain is C57Bl/6. At 20 months of age these mice were euthanized by cervical dislocation, the brain removed from the skull and dissected into regions of interest, the prefrontal cortex was used for the microarray studies.
2015-01-05 | E-GEOD-60911 | biostudies-arrayexpress
Project description:The decline of cognitive function is a feature of normal human aging and is exacerbated in Alzheimer’s disease (AD). DNA repair declines in brain cells during normal aging and even more so in AD. Here we show that experimental reduction in levels of the base excision repair enzyme, DNA polymerase β (Polb) renders neurons vulnerable to age-related dysfunction and degeneration in a mouse model of AD. Whereas 3xTgAD mice exhibit age-related extracellular amyloid b-peptide (Ab) accumulation and cognitive deficits, but no neuronal death, 3xTg/Polb+/- mice accumulates intracellular Ab and neurons die in the hippocampus and cerebral cortex. The DNA repair-deficient 3xTgAD mice exhibited increased DNA strand breaks and apoptotic caspase activation with loss of hippocampal volume, and impaired synaptic plasticity and memory retention. Molecular profiling revealed remarkable similarities in gene expression alterations in brain cells of AD patients and 3xTgAD/Polb+/- mice including multiple abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in oxidative DNA damage processing is sufficient to render neurons vulnerable to AD-related pathogenic molecular and cellular alterations that result in the dysfunction and death of neurons, and associated cognitive deficits.
2015-01-05 | GSE60911 | GEO
Project description:Study of the effects of interleukin 1 beta on transcript expression in ventricular cardiac myocytes
2010-04-01 | E-MEXP-1960 | biostudies-arrayexpress
Project description:Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polb+/- mouse that exacerbates major features of human AD including pTau pathologies, synaptic dysfunction, neuronal death and cognitive impairment. Here we report that 3xTgAD/Polb+/- mice have reduced cerebral NAD+/NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment. NR lessened pTau pathology in both 3xTgAD and 3xTgAD/Polb+/- mice, but had no impact on Abeta accumulation. NR-treated 3xTgAD/Polb+/- mice exhibited reduced DNA damage, neuroinflammation, apoptosis of hippocampal neurons, and increased activity of SIRT3 in the brain. NR improves cognitive function in multiple behavioral tests, and restored hippocampal synaptic plasticity in 3xTgAD mice and 3xTgAD/Polb+/- mice. In general, the deficits and the benefits of NR were greater in 3xTgAD/Polb+/- mice than in 3xTgAD mice. Our findings suggest a pivotal role for cellular NAD+ depletion upstream of neuroinflammation, pTau, DNA damage, synaptic dysfunction and neuronal degeneration in AD. Interventions that bolster neuronal NAD+ levels therefore have potential in AD.
2018-02-26 | GSE109055 | GEO
Project description:Background: We have previously found that overexpression of CHF1/Hey2 in the myocardium prevents the development of phenylephrine-induced hypertrophy and promotes physiological hypertrophy in an aortic banding model. To identify transcriptional pathways regulated by CHF1/Hey2 in hypertrophy, we cultured primary neonatal mouse cardiac myocytes from wild type and transgenic mice overexpressing CHF1/Hey2 and treated them with serum, a potent hypertrophic stimulus. We determined transcriptional profiles by hybridization to Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays. We identified important biological processes regulated by CHF1/Hey2 by Gene Set Analysis using Biological Process Gene Sets from the Gene Ontology Consortium. Results: We found that overexpression of CHF1/Hey2 suppresses gene sets involved in water transport, regulation of adenylate cyclase activity, embryonic eye morphogenesis, gut development and fluid transport after serum stimulation. Genes involved in protein dephosphorylation, in contrast, demonstrate increased expression in myocytes overexpressing CHF1/Hey2, and this increase is independent of serum treatment. Genes overexpressed prior to serum treatment are involved in regulation of transcription factor activity, protein export from the nucleus, and steroid hormone receptor signaling. Genes overexpressed after serum treatment are involved in autophagy, apoptosis and mitochondrial biogenesis. Conclusions: CHF1/Hey2 suppresses fluid transport, activation of adenylate cyclase activity, promotes phosphatase activity, autophagy and regulates other important biological processes likely relevant to hypertrophy. Transgenic Mice and Neonatal Mouse Myocyte Culture: WT no serum, 5; WT with serum, 7; TG no serum, 6; TG with serum, 7.
2010-04-08 | E-GEOD-14288 | biostudies-arrayexpress
Project description:We report a genome-wide study of the role of a muscle-specific Igf2/H19 transcriptional enhancer in global histone modifications in primary mouse myocytes. We generated 1.7 billion bases of sequence from DNA purified by the chromatin immunoprecipitation of H3K36me3 in wild type myocytes and myocytes bearing a deletion of the enhancer. Because H3K36me3 is reported to mark transcribed gene regions, we generated these data to develop a list of genes that are directly or indirectly regulated by this muscle enhancer. This study provides additional insight into how this muscle-specific enhancer potentially regulates a transcriptional network in mouse skeletal myocytes.
2018-07-20 | GSE71227 | GEO
Project description:We report that the winged helix transcription factor FOXA1 is unexpectedly associated with components of single and double stranded-DNA repair complexes. Biochemical studies and high-throughput approaches validated the hierarchical composition of this FOXA1-nucleated machinery and revealed the dependency on FOXA1 for global targeting of the key repair polymerase POLB. Genome-wide DNA methylomes at single-base resolution demonstrated that FOXA1-DNA repair complex is functionally linked to DNA demethylation in a lineage specific fashion. Loss-of-function studies indicate that a significant portion of FOXA1-bound regions display localized reestablishment of methylation and that the subsets with most consistent hypermethylation are represented by active promoters and enhancers that also exhibit the greatest depletion of POLB following FOXA1 removal. Consistently, forced expression of FOXA1 commits its binding sites to an active DNA demethylation in a POLB dependent manner. Finally, we showed that FOXA1-associated DNA demethylation is tightly coupled with genomic targeting of estrogen receptor and estrogen responsiveness. Together, our results link FOXA1-associated DNA demethylation to its transcriptional pioneering.
2016-06-08 | PXD004271 | Pride