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1.
J Dent Res ; 88(10): 910-5, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19783798

ABSTRACT

A primary cilium, a sensory organelle present in almost every vertebrate cell, is regularly described in odontoblasts, projecting from the surfaces of the cells. Based on the hypothesis that the primary cilium is crucial both for dentin formation and possibly in tooth pain transmission, we have investigated the expression and localization of the main cilium components and involvement of the OFD1 gene in tooth morphogenesis. Odontoblasts in vitro express tubulin, inversin, rootletin, OFD1, BBS4, BBS6, ALMS1, KIF3A, PC1, and PC2. In vivo, cilia are aligned parallel to the dentin walls, with the top part oriented toward the pulp core. Close relationships between cilium and nerve fibers are evidenced. Calcium channels are concentrated in the vicinity of the basal body. Analysis of these data suggests a putative role of cilia in sensing the microenvironment, probably related to dentin secretion. This hypothesis is enhanced by the huge defects observed on molars from Ofd1 knockout mice, showing undifferentiated dentin-forming cells.


Subject(s)
Cilia/physiology , Heat-Shock Proteins/physiology , Molar/growth & development , Odontoblasts/physiology , Odontogenesis/physiology , Adolescent , Animals , Calcium Channels/analysis , Calcium Channels/ultrastructure , Cell Cycle Proteins , Cell Movement , Cells, Cultured , Cytoskeletal Proteins/analysis , Dental Pulp/ultrastructure , Dentin/ultrastructure , Group II Chaperonins , Heat-Shock Proteins/analysis , Humans , Kinesins/analysis , Mice , Mice, Knockout , Microtubule-Associated Proteins , Molar/ultrastructure , Molecular Chaperones/analysis , Morphogenesis/physiology , Nerve Fibers/ultrastructure , Proteins/analysis , TRPP Cation Channels/analysis , Transcription Factors/analysis , Tubulin/analysis
2.
Am J Physiol Cell Physiol ; 281(5): C1657-66, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11600430

ABSTRACT

We have designed and synthesized benzo[c]quinolizinium derivatives and evaluated their effects on the activity of G551D cystic fibrosis transmembrane conductance regulator (CFTR) expressed in Chinese hamster ovary and Fisher rat thyroid cells. We demonstrated, using iodide efflux, whole cell patch clamp, and short-circuit recordings, that 5-butyl-6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-91) restored the activity of G551D CFTR (EC(50) = 85 microM) and activated CFTR in Calu-3 cells (EC(50) = 47 microM). MPB-91 has no effect on the ATPase activity of wild-type and G551D NBD1/R/GST fusion proteins or on the ATPase, GTPase, and adenylate kinase activities of purified NBD2. The activation of CFTR by MPB-91 is independent of phosphorylation because 1) kinase inhibitors have no effect and 2) the compound still activated CFTR having 10 mutated protein kinase A sites (10SA-CFTR). The new pharmacological agent MPB-91 may be an important candidate drug to ameliorate the ion transport defect associated with CF and to point out a new pathway to modulate CFTR activity.


Subject(s)
Adenosine Triphosphatases/physiology , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Enzyme Activators/pharmacology , Quinolizines/pharmacology , Adenosine Triphosphatases/metabolism , Animals , CHO Cells , Chloride Channels/drug effects , Chloride Channels/metabolism , Cricetinae , Electrophysiology , Iodides/metabolism , Patch-Clamp Techniques , Phosphorylation , Rats , Rats, Inbred F344 , Thyroid Gland/cytology , Thyroid Gland/drug effects , Thyroid Gland/metabolism
3.
Amino Acids ; 21(2): 151-60, 2001.
Article in English | MEDLINE | ID: mdl-11665811

ABSTRACT

We studied the regulation of taurine transport in ANA1 murine macrophage cell line. Taurine uptake was upregulated by hypertonicity and downregulated by bacterial lypopolysaccharide (LPS) and other stimuli leading to macrophage activation. However combined stimulation with LPS plus hypertonic shock evoked an increase of taurine uptake that was even higher than with hypertonic shock alone. Taurine transport was not modified by LPS in GG2EE macrophages derived from C3H/Hej mouse strain, which harbour a mutated Toll-like receptor 4 (TLR4) and thus are not activated by LPS. The extracellular signal-regulated kinase (ERK) inhibitor PD98059 abrogates the effect of both LPS and hyperosmotic shock on ANA1 taurine uptake, while the p38 inhibitor SB203580 reduces the taurine uptake in control conditions and impairs only the response to hypertonicity. These results suggest that the effect of LPS on taurine transport depends on ERK pathway and can be influenced by environmental conditions.


Subject(s)
Drosophila Proteins , Macrophages/metabolism , Taurine/metabolism , Animals , Biological Transport/physiology , Cell Line , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Hypertonic Solutions , Imidazoles/pharmacology , Lipopolysaccharides/pharmacology , Macrophage Activation/physiology , Macrophages/drug effects , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mice , Mitogen-Activated Protein Kinases/metabolism , Pyridines/pharmacology , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Toll-Like Receptor 4 , Toll-Like Receptors
5.
Gene ; 228(1-2): 181-8, 1999 Mar 04.
Article in English | MEDLINE | ID: mdl-10072771

ABSTRACT

The bovine CaCC protein is a putative Ca2+-dependent Cl- channel of airway epithelial cells. Therefore, CaCC proteins could contribute to transepithelial Cl- transport and accordingly modify the phenotype of cystic fibrosis (CF) patients. We have identified a murine EST containing a full-length cDNA coding for a 902-amino-acid protein highly homologous to bovine CaCC. The murine gene (mCaCC) maps to chromosome 3 at the H2-H3 band and is expressed, as indicated by Northern blot analysis, in mouse skin and kidney but not in brain, heart, lung or testis. RT-PCR indicates a low expression in tracheal epithelial cells. Heterologous expression of mCaCC in Xenopus oocytes elicits membrane currents that are anion-selective and inhibited by DIDS and by niflumic acid, a blocker of the endogenous chloride current in oocytes. The identification of genes belonging to the CaCC family will help to evaluate their role as ion channels or channel regulators and their actual contribution to epithelial chloride transport.


Subject(s)
Calcium/physiology , Chloride Channels/genetics , Genes/genetics , 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology , Amino Acid Sequence , Animals , Blotting, Northern , Cattle , Chloride Channels/administration & dosage , Chromosome Mapping , Expressed Sequence Tags , Female , Gene Expression , In Situ Hybridization, Fluorescence , Ionomycin/pharmacology , Ionophores/pharmacology , Male , Membrane Potentials/drug effects , Mice , Microinjections , Molecular Sequence Data , Niflumic Acid/pharmacology , Oocytes/cytology , Oocytes/drug effects , Oocytes/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Sodium Chloride/pharmacology , Tissue Distribution , Xenopus
6.
Am J Physiol ; 275(5): L917-23, 1998 11.
Article in English | MEDLINE | ID: mdl-9815109

ABSTRACT

We performed Ussing chamber experiments on cultured human bronchial epithelial cells to look for the presence of electrogenic dibasic amino acid transport. Apical but not basolateral L-arginine (10-1, 000 microM) increased the short-circuit current. Maximal effect and EC50 were approximately 3.5 microA/cm2 and 80 microM, respectively, in cells from normal subjects and cystic fibrosis patients. The involvement of nitric oxide was ruled out because a nitric oxide synthase inhibitor (NG-nitro-L-arginine methyl ester) did not decrease the arginine-dependent current. Apical L-lysine, L-alanine, and L-proline, but not aspartic acid, were also effective in increasing the short-circuit current, with EC50 values ranging from 26 to 971 microM. Experiments performed with radiolabeled arginine demonstrated the presence of an Na+-dependent concentrative transporter on the apical membrane of bronchial cells. This transporter could be important in vivo to maintain a low amino acid concentration in the fluid covering the airway surface.


Subject(s)
Amino Acids/pharmacology , Bronchi/physiology , Carrier Proteins/metabolism , Cell Membrane/physiology , Epithelial Cells/physiology , Alanine/pharmacology , Amiloride/pharmacology , Amino Acid Transport Systems , Arginine/pharmacology , Cell Membrane/drug effects , Cells, Cultured , Epithelial Cells/drug effects , Humans , Kinetics , Lysine/pharmacology , Membrane Potentials/drug effects , Membrane Potentials/physiology , Nitric Oxide Donors/pharmacology , Penicillamine/analogs & derivatives , Penicillamine/pharmacology , Proline/pharmacology , S-Nitroso-N-Acetylpenicillamine
7.
Scand J Gastroenterol ; 31(9): 917-20, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8888441

ABSTRACT

BACKGROUND: More than 100 different mutations in the adenomatous polyposis coli (APC) gene have been identified; virtually all lead to the production of a truncated protein. Clinical details of patients with missense mutations undoubtedly cosegregating with the disease have not been reported and may be relevant in understanding the APC protein function. METHODS: In one family with familial adenomatous polyposis (FAP) the APC gene was analyzed by SSCP and sequencing of the aberrant SSCP band. RESULTS: A missense mutation in exon 15 at nucleotide 4921 segregating with the disease was observed. This predicts a tryptophan instead of an arginine at amino acid 1641 of the APC protein. No such mutation was present in 100 control subjects. CONCLUSIONS: In this family the colonic manifestations are as expected for classical FAP. However, the occurrence of congenital hypertrophy of the retinal pigment epithelium is unusual, owing to the inconsistency of this manifestation between family members and because congenital hypertrophy of the retinal pigment epithelium is generally absent when mutations are after codon 1387.


Subject(s)
Adenomatous Polyposis Coli/genetics , Mutation , Adenomatous Polyposis Coli/pathology , Adenomatous Polyposis Coli Protein , Adult , Colon/pathology , Cytoskeletal Proteins/genetics , Exons , Female , Humans , Hypertrophy , Male , Middle Aged , Pigment Epithelium of Eye/pathology , Tryptophan/genetics
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