Glucocorticoids play central roles in the regulation of energy metabolism by shifting it toward catabolism, while AMPK is the master regulator of energy homeostasis, sensing energy depletion and stimulating pathways of increasing fuel uptake and saving on peripheral supplies. We showed here that AMPK regulates glucocorticoid actions on carbohydrate metabolism by targeting the glucocorticoid receptor (GR) and modifying transcription of glucocorticoid-responsive genes in a tissue- and promoter-specific fashion. Activation of AMPK in rats reversed glucocorticoid-induced hepatic steatosis and suppressed glucocorticoid-mediated stimulation of glucose metabolism. Transcriptomic analysis in the liver suggested marked overlaps between the AMPK and glucocorticoid signaling pathways directed mostly from AMPK to glucocorticoid actions. AMPK accomplishes this by phosphorylating serine 211 of the human GR indirectly through phosphorylation and consequent activation of p38 MAPK and by altering attraction of transcriptional coregulators to DNA-bound GR. In human peripheral mononuclear cells, AMPK mRNA expression positively correlated with that of glucocorticoid-responsive GILZ, which correlated also positively with the body mass index of subjects. These results indicate that the AMPK-mediated energy control system modulates glucocorticoid action at target tissues. Since increased action of glucocorticoids is associated with development of metabolic disorders, activation of AMPK could be a promising target for developing pharmacologic interventions to these pathologies.
AMPK regulates metabolic actions of glucocorticoids by phosphorylating the glucocorticoid receptor through p38 MAPK.
Sex
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Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.
Specimen part
View SamplesHypothesis: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups.
Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.
Specimen part
View SamplesThe cerebral cortex underwent a rapid expansion and complexification during recent primate evolution, but the underlying developmental mechanisms remain essentially unknown.
Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.
Age, Specimen part
View SamplesOsteoarthritic cartilage has largely been investigated, however supporting structures as the acetabular labrum are less investigated. In this studies we aimed to identify differences in gene expression between healthy and osteoarthritic labrum cells
Distinct dysregulation of the small leucine-rich repeat protein family in osteoarthritic acetabular labrum compared to articular cartilage.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Disruption of histone methylation in developing sperm impairs offspring health transgenerationally.
Specimen part
View SamplesA fathers lifetime experiences can be transmitted to his offspring to affect
Disruption of histone methylation in developing sperm impairs offspring health transgenerationally.
Specimen part
View SamplesThe delicate interaction between cancer cells and the surrounding stroma plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer.
CD99 is a novel prognostic stromal marker in non-small cell lung cancer.
Specimen part, Subject
View SamplesAffymetrix HuGene ST 1.0 microarrays were used to study and compare gene expression in peripheral blood CD8+ T cells of human patients with Acute Infectious Mononucleosis (AIM; acute EBV infection) and during convalescence (CONV; 6-12 months after AIM visit). Blood samples were drawn from ten human patients with AIM and again during their covalescence (CONV). Peripheral blood mononuclear cells were isolated and cryopreserved. Paired AIM and CONV samples were thawed and CD8+ T cells purified with magnetic beads. RNA was isolated and processed for hybridization according to the Affymetrix protocol
A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection.
Specimen part, Disease stage
View SamplesAnalysis of HeLa cells following depletion of BRCA1 tumor supressor using RNAi against BRCA1. Results provide insight into the molecular mechanisms underlying loss of the BRCA1 function.
BRCA1 represses amphiregulin gene expression.
Treatment
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