Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Different intrinsic alterations of skeletal muscle metabolism and gene expression have been described in chronic heart failure (CHF). As proposed skeletal muscle alterations in CHF may contribute to exercise intolerance and early muscular fatigue. However the exact molecular changes occurring in the skeletal muscle are still unclear. The aim of this study was to characterize the pattern of differential gene expression in an animal model of CHF and to study the regulation of one selected gene. Rats were subjected to
LAD
ligation or sham operation. mRNA was isolated from musculus quadriceps of both groups and differential gene expression was determined by subtractive hybridization. Quantitative RT-PCR and cell culture experiments were performed to further characterize the changed expression of protein phosphatase 2A (
PP2A
) in human skeletal muscle biopsies as well as the cytokine dependent regulation of
PP2A
expression. Out of 800 picked clones differential expression of 24 distinct genes could be identified by sequencing and reverse Northern blotting.
PP2A
expression demonstrated a significant upregulation in skeletal muscle biopsies from patients with CHF as compared to healthy controls (9.7 +/- 1.9 vs. 4.2 +/- 0.7 arbitrary units; p<0.05). Incubation of rat skeletal muscle myoblasts with a combination of TNF-alpha, IL-1beta, and gamma-IFN caused a 3-fold upregulation of
PP2A
expression vs. untreated cells. These results suggest that CHF is accompanied by changes in expression of genes involved in energy metabolism, contractility, and apoptosis in the skeletal muscle. The upregulation of
PP2A
, an important regulator in intracellular signaling and apoptosis, may be due to an increase of inflammatory cytokines.
...
PMID:Differential gene expression in skeletal muscle after induction of heart failure: impact of cytokines on protein phosphatase 2A expression. 1456 76
Toll-like receptors (TLRs) expressed in mast cells play important roles in orchestrating host defence against bacterial pathogens. Previous studies demonstrated that TLR2 agonist tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3Cys) stimulates both degranulation and cytokine production in human mast cells but only induces cytokine production in murine mast cells. To determine the molecular basis for this difference, we utilized a human mast cell line
LAD
2, murine lung and bone marrow-derived mast cells (MLMC and BMMC). We found that Pam3Cys caused a sustained Ca2+ mobilization and degranulation in
LAD
2 mast cells but not in MLMC or BMMC. Despite these differences, Pam3Cys stimulated equivalent chemokine CCL2 generation in all mast cell types tested. Cyclosporin A (CsA), an inhibitor of Ca2+/
calcineurin
-mediated nuclear factor of activated T cells (NFAT) activation, blocked chemokine production in
LAD
2 but not in MLMC or BMMC. In contrast, inhibitors of nuclear factor kappa B (NF-kappaB) completely blocked CCL2 production in MLMC and BMMC but not in
LAD
2 mast cells. Pertussis toxin and U0126, which, respectively, inhibit Galphai, extracellular signal-regulated kinase (ERK) phosphorylation substantially inhibited Pam3Cys-induced CCL2 generation in
LAD
2 mast cells but had little or no effect on chemokine generation in MLMC and BMMC. These findings suggest that TLR2 activation in human
LAD
2 mast cells and MLMC/BMMC promotes the release of different classes of mediators via distinct signalling pathways that depend on Ca2+ mobilization and G protein usage.
...
PMID:Distinct roles of Ca2+ mobilization and G protein usage on regulation of Toll-like receptor function in human and murine mast cells. 1706 16
