ABSTRACT
ABSTRACT: A patient with a large pericardial effusion and impending tamponade exhibited clinical improvement with urgent pericardiocentesis. Further workup ruled minoxidil to be the likely cause of the effusion. After discontinuation of minoxidil, the effusion did not recur.
Subject(s)
Cardiac Tamponade , Pericardial Effusion , Humans , Pericardial Effusion/chemically induced , Minoxidil/adverse effects , Pericardiocentesis/adverse effects , Cardiac Tamponade/chemically inducedABSTRACT
Glucocorticoids elicit a variety of biological responses in skeletal muscle, including inhibiting protein synthesis and insulin-stimulated glucose uptake and promoting proteolysis. Thus, excess or chronic glucocorticoid exposure leads to muscle atrophy and insulin resistance. Glucocorticoids propagate their signal mainly through glucocorticoid receptors (GR), which, upon binding to ligands, translocate to the nucleus and bind to genomic glucocorticoid response elements to regulate the transcription of nearby genes. Using a combination of chromatin immunoprecipitation sequencing and microarray analysis, we identified 173 genes in mouse C2C12 myotubes. The mouse genome contains GR-binding regions in or near these genes, and gene expression is regulated by glucocorticoids. Eight of these genes encode proteins known to regulate distinct signaling events in insulin/insulin-like growth factor 1 pathways. We found that overexpression of p85α, one of these eight genes, caused a decrease in C2C12 myotube diameters, mimicking the effect of glucocorticoids. Moreover, reducing p85α expression by RNA interference in C2C12 myotubes significantly compromised the ability of glucocorticoids to inhibit Akt and p70 S6 kinase activity and reduced glucocorticoid induction of insulin receptor substrate 1 phosphorylation at serine 307. This phosphorylation is associated with insulin resistance. Furthermore, decreasing p85α expression abolished glucocorticoid inhibition of protein synthesis and compromised glucocorticoid-induced reduction of cell diameters in C2C12 myotubes. Finally, a glucocorticoid response element was identified in the p85α GR-binding regions. In summary, our studies identified GR-regulated transcriptional networks in myotubes and showed that p85α plays a critical role in glucocorticoid-induced insulin resistance and muscle atrophy in C2C12 myotubes.
Subject(s)
Gene Expression Regulation , Insulin/metabolism , Muscle Fibers, Skeletal/metabolism , Receptors, Glucocorticoid/chemistry , Animals , Atrophy , Binding Sites , Chromatin Immunoprecipitation , Disease Models, Animal , Genome-Wide Association Study , Genomics , Glucocorticoids/metabolism , Mice , Muscle, Skeletal/metabolism , Muscles/pathology , Oligonucleotide Array Sequence Analysis , Proteolysis , RNA Interference , Signal TransductionABSTRACT
A 34-year-old woman at 18 weeks' gestation experienced shortness of breath and palpitations after receiving her first dose of doxorubicin for right-sided invasive ductal breast carcinoma. Telemetry monitoring found frequent runs of nonsustained ventricular tachycardia that was treated with metoprolol tartrate. No further arrhythmias occurred with subsequent doses of chemotherapy.