Transcription profiling of mouse skeletal muscle treated with drugs and excercise traing
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Vihang Narkar
PROVIDER: E-GEOD-11805 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Exercise activates serine/threonine kinase AMPK and transcriptional factor PPARdelta that re-model metabolism and endurance capacity of skeletal muscle. Whether and how synthetic activation of these molecules regulated muscle gene signature is unknown. We have conducted skeletal muscle microarrays from mice treated with AMPK agoinst (AICAR), PPARdelta agonist (GW1516) or the combination of the two drugs to investigate the individual and interactive effects of the two on muscle genes. Experiment Overall Design: C57Bl/6J mice were treated with Vehicle, AICAR, GW1516 and the combination of two drugs for 6 days, followed by collection of quadriceps for gene expression analysis.
2008-10-21 | E-GEOD-11804 | biostudies-arrayexpress
Project description:Exercise training increases endurance by inducing global gene expression changes in skeletal muscles. The extent to which the genetic effects of exercise can be mimicked by synthetic drugs is unknown. We measured global skeletal muscle expression in sedentary and exercised mice treated with vehicle or PPARdelta ligand GW1516. PPARdelta is a transcriptional regulator of muscle oxidative metabolism and fatigue resistance. Experiment Overall Design: Sedentary and exercise trained C57Bl/6J mice were treated with vehicle or GW1516 for 4 weeks, followed by collection of quadriceps for gene expression analysis.
2008-10-21 | E-GEOD-11803 | biostudies-arrayexpress
Project description:NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass, despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function. Messenger RNA was isolated from quadriceps muscle of mice from three different age groups and three different genotypes. Wildtype mice were aged 4, 7, and 24 months. Mice deficient for Nampt in skeletal muscle (mNKO) were aged 7 months. Mice overexpressing Nampt in skeletal muscle were aged 4 and 24 months.
2016-07-22 | E-GEOD-74570 | biostudies-arrayexpress
Project description:The opioid receptors are important regulators of pain, reward, and addiction. Limited evidence suggests the mu and delta opioid receptors form a heterodimer (MDOR), which may act as a negative feedback brake on opioid-induced analgesia. However, evidence for the MDOR in vivo is indirect and limited, and there are few selective tools available. We recently published the first MDOR-selective antagonist, D24M, allowing us to test the role of the MDOR in mice. We thus co-treated CD-1 mice with D24M and opioids in tail flick, paw incision, and chemotherapy-induced peripheral neuropathy pain models. D24M treatment enhanced oxymorphone anti-nociception in all models by 52.3%-628%. This enhancement could not be replicated with the mu and delta selective antagonists CTAP and naltrindole, and D24M had a mild transient effect in the Rotarod test, suggesting this increase is selective to the MDOR. However, D24M had no effect on morphine or buprenorphine, suggesting that only specific opioids interact with the MDOR. To find a mechanism we performed phosphoproteomic analysis on brainstems of mice. We found that the kinases Src and CaMKII were repressed by oxymorphone, which was restored by D24M. We were able to confirm the role of Src and CaMKII in D24M-enhanced anti-nociception using small molecule inhibitors (KN93, Src-I1). Together these results provide direct in vivo evidence that the MDOR acts as an opioid negative feedback brake, which occurs via the repression of Src and CaMKII signal transduction. These results further suggest that MDOR antagonism could be a means to improve clinical opioid therapy.
2023-03-10 | PXD022106 | Pride
Project description:To reveal the comparative pharmacological mechanism of differential compounds and its combination, we used a custom cNDA microarray to screen gene expression on ischemia mouse hippocampus. Cerebral ischemia was induced in anesthetized mice by urethane (1.5g/kg, i.p) to 38-48g male or female mice by occlusion of the middle cerebral artery (MCA) for 15 minutes twice with microvascular clips, followed by reperfusion for 10 minutes after the first occlusion. Experimental animal were divided into groups: Sham-operated, vehicle (M3,ischemic mice 3 hour;12 hour;24 hour),Baicalin(BA) (5mg/ml), Jasminoidin(JA) (25mg/ml),Jasminoidin(H) (50mg/ml),Cholic acid(CA) (7mg/ml),Concha margaritifera(CM) (50mg/ml), Nimodipine (NI) (50mg/ml),and JA+BA, JA+CA, JA+BA+CA, JA+BA+CA+CM. The prescription of combination therapies was composed of the same ratio on every compound. Treated compound dosage according to 0.2ml physic liquor/100g mouse or rat body weight treated at 1.5h post operation given through tail vein. Sham-operated mice underwent identical procedures except therapy were vehicle (2ml/kg; 100% DMSO). Infarct Volume and Neurological Score were tested to display variation on comeout change. Hippocampus (subfields CA1-4 of Ammon's horn) were carefully dissected out from re-anesthetized mice under RNAase-free conditions, flash frozen and stored at -75 C. Total RNA of each sample was extracted with Trizol reagent (Invitrogen, procedure according to the instruction manual). Three animals per group were pooled and homogenized in denaturing solution with a Polytron. Three pooled per group and nine times repeted microarray experiments of each pooled were preformed. Each microarray contained 374 cDNA derived from cDNA library of mouse brain (Invitrogen, Cat.1065-025). Plasmid magnified using Invitrogen provided library. Design and synthesize Primer according the information provided by selected genes.Total gene segment is 416, two of them is control(lambda-A and pUC19). The criterion of qualified PCR extending is: the total gained volume of the purpose strap DNA is greater or equal to 7?g;the purpose strap DNA gained volume/total DNA gained volume is greater or equal to 80%.Finally, the DNA concentration is adjusted to 0.5 ?g/ ?l.After refinded PCR_for every gene, 2?l DNA solution was taken to proceeding electrophoresis on the electrophoresis condition of 2%Gel.Then fix quantify analysis according electrophoresis photo have taken.Choosing 5 PCR refined products sequencing from two direction after amplification.These 5 genes all chosen from UniGene sample which marked by ?,one of them is used Dalian ? as cyclostyle to amplification.The five sequence genes was certified as aimed gene segment by Blast(Completed in TaKaRa(Dalian))
2010-01-01 | E-TABM-612 | biostudies-arrayexpress
Project description:To explore the inner mechanism of components and combination of Qingkailing inject fluid,compare the gene express and pharmacological pathway after experimental stroke mice.
2010-12-30 | E-TABM-662 | biostudies-arrayexpress
Project description:Cancer cachexia, highly prevalent in lung cancer, is a debilitating syndrome characterized by involuntary loss of skeletal muscle mass, and is associated with poor clinical outcome, decreased survival and negative impact on tumor therapy. Various lung tumor-bearing animal models have been used to explore underlying mechanisms of cancer cachexia. However, these models do not simulate anatomical and immunological features key to lung cancer and associated muscle wasting. Overcoming these shortcomings is essential to translate experimental findings into the clinic. We therefore evaluated whether a syngeneic, orthotopic lung cancer cachexia (OLCC) mouse model replicates systemic and muscle-specific alterations associated with human lung cancer cachexia. Immune competent, 11 weeks old male 129S2/Sv mice, were randomly allocated to either (1) sham control group or (2) tumor-bearing (OLCC) group. Syngeneic lung epithelium-derived adenocarcinoma cells (K-rasG12D; p53R172HΔG) were inoculated intrapulmonary into the left lung lobe of the mice. Body weight and food intake were measured daily. At baseline and weekly after surgery, grip strength was measured and tumor growth and muscle volume were assessed using micro cone beam CT imaging. After reaching predefined surrogate survival endpoint, animals were euthanized and skeletal muscles of the lower hind limbs were collected forRNA sequencing. RNA sequencing was performed on the Illumina NovasSeq 6000.
2023-04-03 | E-MTAB-12780 | biostudies-arrayexpress
Project description:Background: Beta-adrenergic receptor agonists (BA) induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. We chose to evaluate global changes in gene expression by utilizing the Affymetrix platform to identify gene expression changes in mouse skeletal muscle. Changes in gene expression were evaluated 24 h (1D) and 10 days (10D) after administration of the BA clenbuterol. Results: Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P < 0.01) and increased body weight gain (P < 0.05) 24 h or 10 d, respectively, after initiation of clenbuterol treatment. A total of 22,787 probesets were evaluated with 113 probesets defined as differentially expressed based on a false discovery rate of 10%. Differential mRNA abundance of four of these genes was validated in an independent experiment by quantitative PCR. Patterns of gene expression change observed from the microarray data suggested more genes are differentially regulated after 24 h than 10 d of BA administration. Functional characterization of differentially expressed genes revealed several categories that participate in biological processes important to skeletal muscle growth, including regulators of transcription and translation, mediators of cell-signaling pathways, and genes involved in polyamine metabolism. Included within these lists were several genes previously associated with myogenic differentiation, along with multiple genes known to promote a general up-regulation of translation. Conclusions: Global evaluation of gene expression after administration of clenbuterol identified changes gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in the mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on the proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Additionally, increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators, rather than a sustained up-regulation of gene expression at the transcriptional level. Additionally, numerous other genes and physiological pathways were identified that will be important targets for further investigations of the hypertrophic effect of BA on skeletal muscle. Experiment Overall Design: A total of 27 mice were used to represent three treatments. Hybridizations were done using RNA pools from 3 mice, with 3 pools (replicates) per treatment. Treatments included control, 1 day of clenbuterol administration, and 10 days of clenbuterol administration. Data represent skeletal muscle gene expression.
2008-06-13 | E-GEOD-4490 | biostudies-arrayexpress
Project description:The nucleosome signature reflects the cellular epigenetic memory and contributes to the cellular phenotype and function. Obesity and type 2 diabetes pathogenesis is largely dependent on environmentally-induced epigenetic modifications and is marked by skeletal muscle insulin resistance; however, no in vivo skeletal muscle nucleosome maps exist to date. Herein, whole genome nucleosome maps via MNase-seq in skeletal muscle of mice on a low fat, high fat or high fat diet with the chromatin modifier sodium butyrate show that complex interactions among mitochondrial function, the tissue microenvironment, cellular phenotype and nucleosome landscape determine whole body phenotype and insulin resistance. Skeletal muscle samples (n=5 per group) were pooled after homogenization under liquid nitrogen with a motar and pestle to give one sample per group for MNase-seq
2012-05-11 | E-GEOD-37913 | biostudies-arrayexpress
Project description:Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects other organs at a distance. We developed mouse models to ask if inhibition of EglN1, which senses oxygen and regulates the HIF transcription factor, could suffice to mediate local and remote ischemic preconditioning. We used microarrays to detail the global expression changes induced when the oxygen sensor EglN1 is genetically deleted from skeletal muscle cells. We also used microarrays to assess the transcriptome alterations that occur in mouse hearts with pharmacologic inhibition of EglN1, using the EglN inhibitor FG-4497. We generated mice with a tamoxifen-inducible model of EglN1 loss using a floxxed EglN1 locus with skeletal muscle-specific CRE recombinase. WT mice and mice with the floxxed EglN1 locus were exposed to tamoxifen. Mouse skeletal muscle was isolated for RNA extraction and hybridization on Affymetrix microarrays. In a related experiment, mice were treated with the EglN inhibitor FG-4497, and RNA from their heart tissue was analyzed by microarray for transcriptome alterations compared to control hearts.
2016-02-11 | E-GEOD-77789 | biostudies-arrayexpress