Search results for "ion channels"
showing 10 items of 137 documents
The Vibrio choleare haemolysin anion channel is required for cell vacuolation and death
2002
SummarySeveral strains of Vibrio cholerae secrete ahaemolytic toxin of 63kDa, termed V. cholerae cytolysin (VCC). This toxin causes extensive vacuo-lation and death of cells in culture and forms ananion-selective channel in planar lipid bilayers and incells. Here, we identify inhibitors of the VCC anionchannel and show that the formation of the anionchannel is necessary for the development of the vacuoles and for the cell death induced by this toxin. Using markers of cell organelles, we show that vacuoles derive from different intracellular com-partments and we identify the contribution of lateendosomes and of the trans -Golgi network in vacuolebiogenesis.Introduction The Gram-negative bact…
CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia
2005
Contains fulltext : 47591.pdf (Publisher’s version ) (Closed access) Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutatio…
A constitutive BCL2 down-regulation aggravates the phenotype of PKD1-mutant-induced polycystic kidney disease
2017
IF 5.340; International audience; The main identified function of BCL2 protein is to prevent cell death by apoptosis. Mice knock-out for Bcl2 demonstrate growth retardation, severe polycystic kidney disease (PKD), gray hair and lymphopenia, and die prematurely after birth. Here, we report a 40-year-old male referred to for abdominal and thoracic aortic dissection with associated aortic root aneurysm, PKD, lymphocytopenia with a history of T cell lymphoblastic lymphoma, white hair since the age of 20, and learning difficulties. PKD, which was also detected in the father and sister, was related to an inherited PKD1 mutation. The combination of PKD with gray hair and lymphocytopenia was also r…
Effect of ouabain and furosemide on erythrocyte sodium and phosphate transport.
1981
The effects of ouabain and furosemide on the unidirectional efflux of sodium and phosphate ions were studied in freshly drawn human red blood cells (RBCs). In the presence of physiologic concentrations of sodium and potassium the rate of sodium efflux was reduced by 74% due to ouabain sensitivity. Furosemide (1.0 mmol/l) reduced ouabain-insensitive sodium transport rate by a further 50%. Thus, 13% of total sodium efflux was inhibited by furosemide when ouabain was present. In the absence of ouabain, however, furosemide inhibited 31% of total sodium transport, indicating that it also affected ouabain-sensitive sodium efflux. Phosphate transfer of RBCs was almost 1.0 mmol/l RBCs per hour. Ery…
Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia…
2008
Background: The mechanisms of progression from fatty liver to steatohepatitis and cirrhosis are not well elucidated. Mitochondrial dysfunction represents a key factor in the progression of non-alcoholic steatohepatitis (NASH) as mitochondria are the main cellular site of fatty acid oxidation, ATP synthesis and reactive oxygen species (ROS) production. Aims: (1) To evaluate the role of the uncoupling protein 2 in controlling mitochondrial proton leak and ROS production in NASH rats and humans; and (2) to assess the acute liver damage induced by ischaemia–reperfusion in rats with NASH. Methods: Mitochondria were extracted from the livers of NASH humans and rats fed a methionine and choline de…
Immunohistochemical profile of human pancreatic pacinian corpuscles.
2010
To analyze the immunohistochemical profile of the human pancreatic pacinian corpuscles in comparison with that of the cutaneous pacinian corpuscles. In addition, we studied a Pacinilike corpuscle found in the adventitia of a pancreatic artery.We used immunohistochemistry to detect specific antigens for corpuscular constituents, specific antibodies for the identification of Adelta- and C-sensory fibers and for the detection of several growth factor receptors, and some members of the degenerin/epithelial Na channel superfamily of proteins.Approximately 62% of pancreatic pacinian corpuscles have 2 to 10 axonic profiles each enclosed by its own inner core: 1 or 2 of these axonic profiles displa…
The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis
2015
Background & Aims Uncoupling protein 2 - UCP2 - regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The −866 G>A UCP2 promoter region polymorphism has been linked to insulin resistance and lipid metabolism. The aim of this study was to assess whether the −866 G>A UCP2 polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP2 expression. Methods We considered 688 Italian patients who underwent liver biopsy for suspected NASH, and 232 healthy controls. The UCP2 −866 G>A polymorphism was determined by allele specific oligonucleotide probes, hepatic UCP2 mRNA levels …
Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation.
2014
We have previously demonstrated that menthol reduces murine gastric tone in part through a neural mechanism, involving adrenergic pathways and reduction of ongoing release of acetylcholine from enteric nerves. In the present study we aimed to verify whether the gastric relaxation to menthol may be triggered by interaction with neural receptors or ionic channels proteins, such as transient receptor potential (TRP)-melastatin8 (TRPM8), TRP-ankyrin 1 (TRPA1), 5-hydroxytriptamine 3 (5-HT3) receptor or cholinergic nicotinic receptors. Spontaneous mechanical activity was detected in vitro as changes in intraluminal pressure from isolated mouse stomach. Menthol (0.3-30 mM) induced gastric relaxati…
Structural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism
2012
N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that contribute to the signal transmission in the central nervous system. NMDA receptors are heterotetramers that usually consist of two GluN1 and GluN2 monomers. The extracellular ligand-binding domain (LBD) of a monomer is comprised of discontinuous segments that form the functional domains D1 and D2. While the binding of a full agonist glycine to LBD of GluN1 is linked to cleft closure and subsequent ion-channel opening, partial agonists are known to activate the receptor only sub-maximally. Although the crystal structures of the LBD of related GluA2 receptor explain the mechanism for the partial a…
Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells
2015
Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against canc…