Gene expresssion profiles in PPARalpha-Serine280 phosphorylation mutants
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE112309 | GEO | 2019/03/11
REPOSITORIES: GEO
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Project description:Gene expresssion profiles in PPARalpha-Serine280 phosphorylation mutants
| PRJNA445605 | ENA
Project description:GSK-3 is a serine-threonine protein kinase and consists of two isoforms, GSK-3alpha and GSK-3beta. GSK-3alpha and GSK-3beta are inactivated by phosphorylation at Ser21 and Ser9, respectively. GSK-3alpha Ser21Ala and GSK-3beta Ser9Ala phosphorylation-resistant knock-in mice have constitutively active form of GSK-3.
2019-03-11 | GSE112158 | GEO
Project description:GSK-3 is a serine-threonine protein kinase and consists of two isoforms, GSK-3alpha and GSK-3beta. GSK-3alpha and GSK-3beta are inactivated by phosphorylation at Ser21 and Ser9, respectively. GSK-3alpha Ser21Ala and GSK-3beta Ser9Ala phosphorylation-resistant knock-in mice have constitutively active form of GSK-3.
2019-03-11 | GSE112159 | GEO
Project description:Mutations in KRAS occur in a variety of tumors of epithelial origin, driving the oncogenic phenotype.The NF-kB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently TAK1, an upstream regulator of IKK which controls canonical NF-kB, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS+ colorectal cancer cell growth and survival. Here we show that GSK-3alpha is upregulated by KRAS leading to interaction with TAK1 to stabilize the TAK1/TAB complex to promote IKK activity. Additionally, GSK-3alpha is required for promoting critical non-canonical NF-kB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, consistent with loss of expression of genes such as c-myc and TERT. These data identify GSK-3alpha as a key downstream effector of oncogenic RAS via its ability to coordinately regulate distinct NF-kB signaling pathways GSK-3 inhibition at 2 and 8 hours
2013-05-31 | E-GEOD-42559 | biostudies-arrayexpress
Project description:Cardiac-specific PPARalpha transgenic (Tg-PPARalpha) mice show mild cardiac hypertrophy and systolic dysfunction. The failing heart phenotypes observed in Tg-PPARalpha are exacerbated by crossing with cardiac-specific Sirt1 transgenic (Tg-Sirt1) mice, whereas Tg-Sirt1 mice themselves do not show any cardiac hypertrophy or systolic dysfunction. To investigate the mechanism leading to the failing heart phenotypes in TgPPARalpha/Tg-Sirt1 bigenic mice, microarray analyses were performed. The microarray analyses revealed that many ERR target genes were downregulated in Tg-PPARalpha and in Tg-Sirt1, and they were further downregulated in the Tg-PPARalpha/Tg-Sirt1 bigenic mice.
2011-12-01 | GSE33101 | GEO
Project description:Mutations in KRAS occur in a variety of tumors of epithelial origin, driving the oncogenic phenotype.The NF-kB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently TAK1, an upstream regulator of IKK which controls canonical NF-kB, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS+ colorectal cancer cell growth and survival. Here we show that GSK-3alpha is upregulated by KRAS leading to interaction with TAK1 to stabilize the TAK1/TAB complex to promote IKK activity. Additionally, GSK-3alpha is required for promoting critical non-canonical NF-kB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, consistent with loss of expression of genes such as c-myc and TERT. These data identify GSK-3alpha as a key downstream effector of oncogenic RAS via its ability to coordinately regulate distinct NF-kB signaling pathways
2013-05-31 | GSE42559 | GEO
Project description:This experiment was conducted to identify target genes of the peroxisome proliferator-activated receptor alpha (PPARa) in skeletal muscle of transgenic mice that overexpressed PPARa. The following abstract from the published manuscript describes the major findings of this work. A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes.Finck BN, Bernal-Mizrachi C, Han DH, Coleman T, Sambandam N, LaRiviere LL, Holloszy JO, Semenkovich CF, Kelly DP. The role of the peroxisome proliferator-activated receptor-alpha (PPARalpha) in the development of insulin-resistant diabetes was evaluated using gain- and loss-of-function approaches. Transgenic mice overexpressing PPARalpha in muscle (MCK-PPARalpha mice) developed glucose intolerance despite being protected from diet-induced obesity. Conversely, PPARalpha null mice were protected from diet-induced insulin resistance in the context of obesity. In skeletal muscle, MCK-PPARalpha mice exhibited increased fatty acid oxidation rates, diminished AMP-activated protein kinase activity, and reduced insulin-stimulated glucose uptake without alterations in the phosphorylation status of key insulin-signaling proteins. These effects on muscle glucose uptake involved transcriptional repression of the GLUT4 gene. Pharmacologic inhibition of fatty acid oxidation or mitochondrial respiratory coupling prevented the effects of PPARalpha on GLUT4 expression and glucose homeostasis. These results identify PPARalpha-driven alterations in muscle fatty acid oxidation and energetics as a potential link between obesity and the development of glucose intolerance and insulin resistance. Keywords: genetic modification
2006-09-08 | GSE5777 | GEO
Project description:Findings suggest that PPARalpha plays a decisive role in the development of hypertrophy, affecting the functional outcome of the heart. Unfortunately, information on the nature of PPARalpha-dependent processes in cardiac hypertrophy is fragmentary and incomplete. The primary aim of this study was to identify the processes and signaling pathways regulated by PPARalpha in hearts challenged by a chronic pressure overload by means of whole genome transcriptomic analysis. Second, we wanted to gain insight how PPARalpha modulates the identified processes, e.g. by trans-activation or by trans-repression. Keywords: 28 days of TAC
2008-08-06 | GSE12337 | GEO
Project description:Toxicogenomic Dissection of the Perfluorooctanoic Acid (PFOA) Transcript Profile in Mouse Liver: Evidence for the Involvement of Nuclear Receptors PPARalpha and CAR; We performed a toxicogenomics dissection of the transcript profiles in the mouse liver after exposure to PFOA. We uncovered classes of genes that were regulated independently of PPARalpha. Some of these genes, including those involved in lipid metabolism, may be regulated by PPARbeta/delta or PPARgamma, whereas others, such as those involved in xenobiotic metabolism are likely regulated through CAR. Experiment Overall Design: 129S1/SvlmJ wild-type and PPARalpha-null mice were exposed to 3 mg/kg/day PFOA or water for 7 days. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 16 samples, with four mice in each of the 4 treatment groups, were analyzed.
2008-06-16 | E-GEOD-9786 | biostudies-arrayexpress
Project description:A functional interaction between peroxisome proliferator-activated receptor alpha (PPARalpha) and components of the circadian clock has been suggested; however, it remains to be clarified whether those transcriptional factors interact with each other to regulate the expression of their target genes. In this study, we used a ligand of PPARalpha, bezafibrate, to search the PPARalpha-regulated genes that express in a CLOCK-dependent circadian manner. Microarrays analyses using hepatic RNA isolated from bezafibrate treated-wild type, Clock mutant (Clk/Clk), and PPARalpha-null mice revealed that 136 genes are transcriptionally regulated by PPARalpha in a CLOCK-dependent manner.
2010-06-15 | GSE20513 | GEO