Search results for "Inositol phosphate"
showing 10 items of 26 documents
Sphingolipids and Inositol Phosphates Regulate the Tau Protein Phosphorylation Status in Humanized Yeast
2020
Hyperphosphorylation of protein tau is a hallmark of Alzheimer’s disease (AD). Changes in energy and lipid metabolism have been correlated with the late onset of this neurological disorder. However, it is uncertain if metabolic dysregulation is a consequence of AD or one of the initiating factors of AD pathophysiology. Also, it is unclear whether variations in lipid metabolism regulate the phosphorylation state of tau. Here, we show that in humanized yeast, tau hyperphosphorylation is stimulated by glucose starvation in coincidence with the downregulation of Pho85, the yeast ortholog of CDK5. Changes in inositol phosphate (IP) signaling, which has a central role in energy metabolism, altere…
Functional, biochemical and morphological studies on human bronchi after cryopreservation
1995
1. Human isolated bronchi have been investigated as fresh tissue or after storage (7 and 30 days) at -196 degrees C in foetal calf serum containing 1.8 M dimethyl sulphoxide. 2. After cryopreservation, the maximal contractile response to acetylcholine (3 mM) was reduced (approximately 25%) but the difference did not reach significance statistically. Maximal responses to other spasmogens tested (histamine, [Nle10]NKA(4-10), bradykinin, leukotriene D4, U46619, and KCl) did not differ between unfrozen and frozen/thawed tissues. The sensitivity of cryopreserved tissues to the constrictor agents tested was similar to that of fresh tissues. 3. The accumulation of inositol phosphates produced by a…
Na+ ions binding to the bradykinin B2 receptor suppress agonist-independent receptor activation.
1996
Control of the balance between receptor activation and inactivation is a prerequisite for seven transmembrane domain (7TM) receptor function. We asked for a mechanism to stabilize the inactive receptor conformation which prevents agonist-independent receptor activation. Na+ ions have reciprocal effects on agonist versus antagonist interaction with various 7TM receptors. To investigate the Na+ dependence of receptor activation we chose the bradykinin B2 receptor as a prototypic 7TM receptor. Decrease of the intracellular Na+ content from 40 mM to 10 mM of COS-1 cells transiently expressing rat B2 receptors activated the B2 receptor in the absence of agonist as shown by a 3-fold increase in t…
Activation of phospholipases C and D by the novel metabotropic glutamate receptor agonist tADA.
1997
Abstract In hippocampal slices taken from 8-day-old rats, trans-azetidine-2,4-dicarboxylic acid (tADA), a novel glutamatergic agonist acting preferentially at class I mGluR receptors, activates phosphoinositide and phosphatidylcholine hydrolysis with widely different potencies. Inositol phosphate formation was maximally increased at 10 μM tADA ( ec 50: 1.2 μM), while phospholipase D activation was observed at a tADA concentration of 1 mM. This is the first report of a tADA-induced phospholipase D activity. © 1997 Elsevier Science Ltd. All rights reserved.
Progesterone increases basal 3',5'-cyclic adenosine monophosphate formation and down-regulates the agonist-induced inositol phosphates generation in …
1992
Whether the placenta is a target tissue for estrogens and progesterone, and their putative mechanism of action, is still a controversial question in the literature. The effect of progesterone and estradiol on 3′,5′-cyclic adenosine monophosphate (cAMP) and inositol phosphates generation in human term placenta was investigated. Placental explants were incubated in vitro for up to 48 h in the absence and in the presence of estradiol, progesterone or both steroids (0.1 μmol/l final concentration in all cases), and were stimulated with terbutaline, a β-adrenergic agonist, (0.1 mmol/l) or angiotensin II(1 μmol/l), The cAMP content was measured by a competitive protein binding assay, and the gene…
Expression of metabotropic glutamate receptors in murine thymocytes and thymic stromal cells
2000
RT-PCR combined with immunoblotting showed the expression of group-I (mGlu1 and 5) and group-II (mGlu2 and 3) metabotropic glutamate receptors in whole mouse thymus, isolated thymocytes and TC-1S thymic stromal cell line. Cytofluorimetric analysis showed that mGlu-5 receptors were absent in CD4(-)/CD8(-) but present in more mature CD4(+) CD8(+) and CD4(+)CD8(-) thymocytes. mGlu-1a receptors showed an opposite pattern of expression with respect to mGlu5, whereas mGlu2/3 receptor expression did not differ between double negative and double positive cells. mGlu receptors expressed in both thymic cell components were functional, as indicated by measurements of polyphosphoinositide hydrolysis or…
Interaction of Neuronal Calcium Sensor-1 (NCS-1) with Phosphatidylinositol 4-Kinase β Stimulates Lipid Kinase Activity and Affects Membrane Trafficki…
2001
Phosphatidylinositol 4-kinases (PI4K) catalyze the first step in the synthesis of phosphatidylinositol 4,5-bisphosphate, an important lipid regulator of several cellular functions. Here we show that the Ca(2+)-binding protein, neuronal calcium sensor-1 (NCS-1), can physically associate with the type III PI4Kbeta with functional consequences affecting the kinase. Recombinant PI4Kbeta, but not its glutathione S-transferase-fused form, showed enhanced PI kinase activity when incubated with recombinant NCS-1, but only if the latter was myristoylated. Similarly, in vitro translated NCS-1, but not its myristoylation-defective mutant, was found associated with recombinant- or in vitro translated P…
Polyphosphoinositide Metabolism and Golgi Complex Morphology in Hippocampal Neurons in Primary Culture is Altered by Chronic Ethanol Exposure
2012
Aims : Ethanol affects not only the cytoskeletal organization and activity, but also intracellular trafficking in neurons in the primary culture. Polyphosphoinositide (PPIn) are essential regulators of many important cell functions, including those mentioned, cytoskeleton integrity and intracellular vesicle trafficking. Since information about the effect of chronic ethanol exposure on PPIn metabolism in neurons is scarce, this study analysed the effect of this treatment on three of these phospholipids. Methods : Phosphatidylinositol (PtdIns) levels as well as the activity and/or levels of enzymes involved in their metabolism were analysed in neurons chronically exposed to ethanol. The level…
Chromatin remodeling regulation by small molecules and metabolites.
2010
The eukaryotic genome is a highly organized nucleoprotein structure comprising of DNA, histones, non-histone proteins, and RNAs, referred to as chromatin. The chromatin exists as a dynamic entity, shuttling between the open and closed forms at specific nuclear regions and loci based on the requirement of the cell. This dynamicity is essential for the various DNA-templated phenomena like transcription, replication, and repair and is achieved through the activity of ATP-dependent chromatin remodeling complexes and covalent modifiers of chromatin. A growing body of data indicates that chromatin enzymatic activities are finely and specifically regulated by a variety of small molecules derived f…
Yunis-Varón Syndrome Is Caused by Mutations in FIG4, Encoding a Phosphoinositide Phosphatase
2013
Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of FIG4 in affected individuals from three unrelated families. FIG4 encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P(2) levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of Fig4-null mouse fibroblasts. Homozygous Fig4-null mice exhibit features of YVS, including neurodegeneration and enlarg…