9 research outputs found
Volume-sensitive outwardly rectifying chloride channel blockers protect against high glucose-induced apoptosis of cardiomyocytes via autophagy activation
BK channels affect glucose homeostasis and cell viability of muring pancreatic beta cells
AIMS/HYPOTHESIS: Evidence is accumulating that Ca(2+)-regulated K(+) (K(Ca)) channels are important for beta cell function. We used BK channel knockout (BK-KO) mice to examine the role of these K(Ca) channels for glucose homeostasis, beta cell function and viability. METHODS: Glucose and insulin tolerance were tested with male wild-type and BK-KO mice. BK channels were detected by single-cell RT-PCR, cytosolic Ca(2+) concentration ([Ca(2+)](c)) by fura-2 fluorescence, and insulin secretion by radioimmunoassay. Electrophysiology was performed with the patch-clamp technique. Apoptosis was detected via caspase 3 or TUNEL assay. RESULTS: BK channels were expressed in murine pancreatic beta cells. BK-KO mice were normoglycaemic but displayed markedly impaired glucose tolerance. Genetic or pharmacological deletion of the BK channel reduced glucose-induced insulin secretion from isolated islets. BK-KO and BK channel inhibition (with iberiotoxin, 100 nmol/l) broadened action potentials and abolished the after-hyperpolarisation in glucose-stimulated beta cells. However, BK-KO did not affect action potential frequency, the plateau potential at which action potentials start or glucose-induced elevation of [Ca(2+)](c). BK-KO had no direct influence on exocytosis. Importantly, in BK-KO islet cells the fraction of apoptotic cells and the rate of cell death induced by oxidative stress (H(2)O(2), 10–100 μmol/l) were significantly increased compared with wild-type controls. Similar effects were obtained with iberiotoxin. Determination of H(2)O(2)-induced K(+) currents revealed that BK channels contribute to the hyperpolarising K(+) current activated under conditions of oxidative stress. CONCLUSIONS/INTERPRETATION: Ablation or inhibition of BK channels impairs glucose homeostasis and insulin secretion by interfering with beta cell stimulus–secretion coupling. In addition, BK channels are part of a defence mechanism against apoptosis and oxidative stress
Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells
Nitric oxide treatments as adjuncts to reperfusion in acute myocardial infarction: a systematic review of experimental and clinical studies
FKBP (FK506 Binding Protein)
In the 70s, after a decade from the purification of cyclosporine, a selective immunosuppressant
agent and potent tool in transplantation medicine, a novel molecule was purified from bacteria
Streptomyces tsukubaensis. This molecule, called FK506, showed the same selective
immunosuppressant action as cyclosporine but was 10 to 100 fold more potent.
In an attempt to clarify the molecular mechanism through which the new drug exerted such a
selective effect on T-cells activation, two laboratories identified the cytosolic receptor for FK506.
This so-called FK506 binding protein (FKBP) was purified from bovine thymus, human spleen, and
Jurkat T-cell line. The isolated FKBP had an approximate molecular mass of 14 kDa and showed
an isomerase activity similar to the recently purified cyclosporine-binding protein, cyclophilin, but, it
was inhibited by FK506 and rapamycin but not cyclosporine. The
subsequent cloning of FKBP gene revealed that FKBP and cyclophilin had dissimilar sequences in
spite of their common enzymatic activity. The identified FKBP gene encoded for a protein of 108
aminoacids with a relative molecular mass of 11,819. For this reason, the progenitor of this
nascent class of proteins was later known as FKBP12.
The subsequent studies showed that FKBP12 was just a member of a ubiquitous and evolutionarily
conserved sub-family of proteins which differ from each other in their molecular weight and
structure. All FKBPs share a highly conserved domain, termed “FK-12 like domain”, capable of
binding to FK506 and exerting isomerase properties, i.e. interconversion from cis-to-trans and
trans-to-cis of peptide bonds involving proline, on protein substrates.
A schematic historical background of the 17 FKBPs so far identified is shown. A general
overview of FKBP structure, function and eventually associated disease is given in this
monograph, with the order of proteins following the chronology of discovery
Imaging techniques for assessment of inflammatory bowel disease: Joint ECCO and ESGAR evidence-based consensus guidelines
The management of patients with IBD requires evaluation with objective tools, both at the time of diagnosis and throughout the course of the disease, to determine the location, extension, activity and severity of inflammatory lesions, as well as, the potential existence of complications. Whereas endoscopy is a well-established and uniformly performed diagnostic examination, the implementation of radiologic techniques for assessment of IBD is still heterogeneous; variations in technical aspects and the degrees of experience and preferences exist across countries in Europe. ECCO and ESGAR scientific societies jointly elaborated a consensus to establish standards for imaging in IBD using magnetic resonance imaging, computed tomography, ultrasonography, and including also other radiologic procedures such as conventional radiology or nuclear medicine examinations for different clinical situations that include general principles, upper GI tract, colon and rectum, perineum, liver and biliary tract, emergency situation, and the postoperative setting. The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas such as the comparison of diagnostic accuracy between different techniques, the value for therapeutic monitoring, and the prognostic implications of particular findings. © 2013 European Crohn's and Colitis Organisation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe