Effects of the Chemical Chaperone 4-Phenylbutylate on the Function of the Serotonin Transporter (SERT) Expressed in COS-7 Cells

スポンサーリンク

概要

• 論文の詳細を見る

• The serotonin transporter (SERT) is involved in various psychiatric disorders, including depression and autism. Recently, chemical chaperones have been focused as potential therapeutic drugs that can improve endoplasmic reticulum (ER) stress–related pathology. In this study, we used SERT-transfected COS-7 cells to investigate whether 4-phenylbutylate (4-PBA), a chemical chaperone, affects the membrane trafficking and uptake activity of SERT. Treatment with 4-PBA for 24 h dose-dependently increased the uptake activity of SERT. In accordance with increased SERT activity, the expression of maturely glycosylated SERT was increased, while the expression of immaturely glycosylated SERT was decreased. This finding suggests that 4-PBA increased the functional SERT with mature glycosylation via accelerating its folding and trafficking. 4-PBA also increased the activity of the C-terminus-deleted mutant SERT (SERTΔCT), which was stacked in the ER, and decreased SERTΔCT-induced ER stress, further supporting the idea that 4-PBA acts as a chemical chaperone for SERT. Imaging studies showed that fluorescence-labeled SERT was gradually and significantly translocated to the plasma membrane by 4-PBA. These results suggest that 4-PBA and related drugs can potentially affect serotonergic neural transmission by functioning as chaperones, thereby providing a novel therapeutic approach for SERT-related diseases.

著者

• Yamamoto Hikaru

  Depart Of Physics Kyoto University

• Hide Izumi

  Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro

• Sakai Norio

  Department Of Biopharmaceutics And Drug Rational Research Center School Of Pharmacy Tokyo University

• Fujiwara Masayuki

  Department Of Applied Physics Osaka University:(present Address) Asada Fundamental Research Laborato

• Tanaka Shigeru

  Department Of Applied Chemistry Faculty Of Science And Technology Keio University

• Seki Takahiro

  Department Of Applied Physics Nagoya University

• Yamamoto Hikaru

  Department of Molecular and Pharmacological Neuroscience, Institute of Biomedical & Health Sciences, Hiroshima University, Japan

• Sakai Norio

  Department of Molecular and Pharmacological Neuroscience, Institute of Biomedical & Health Sciences, Hiroshima University, Japan

• Fujiwara Masayuki

  Department of Molecular and Pharmacological Neuroscience, Institute of Biomedical & Health Sciences, Hiroshima University, Japan

• Miyagi Tatsuhiro

  Department of Molecular and Pharmacological Neuroscience, Institute of Biomedical & Health Sciences, Hiroshima University, Japan

• Tanaka Shigeru

  Department of Molecular and Pharmacological Neuroscience, Institute of Biomedical & Health Sciences, Hiroshima University, Japan

関連論文

• Experience-dependent orientation plasticity in the visual cortex of rats chronically exposed to a single orientation
• The C-Terminal Region of Serotonin Transporter Is Important for Its Trafficking and Glycosylation
• Effects of SO_2 on Respiratory System of Adult Miyakejima Resident 2 Years after Returning to the Island
• Analysis of the stable levels of messenger RNA derived from different polymorphic alleles in the vitamin D receptor gene
• Fragmentation of Protein Kinase N (PKN) in the Hydrocephalic Rat Brain
• Antiepileptic Effects of Single and Repeated Oral Administrations of S-312-d, a Novel Calcium Channel Antagonist, on Tonic Convulsions in Spontaneously Epileptic Rats
• Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT_ Receptor
• IV F10 Abnormal excitability of hippocampal CA3 pyramidal neurons involving abnormal Ca2^+ activity in Noda epileptic rats
• Congo Red, an Amyloid-Inhibiting Compound, Alleviates Various Types of Cellular Dysfunction Triggered by Mutant Protein Kinase Cγ That Causes Spinocerebellar Ataxia Type 14 (SCA14) by Inhibiting Oligomerization and Aggregation
• Sleep disordered breathing in childhood-onset acid maltase deficiency
• Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation
• Novel mutation of gene coding for glial fibrillary acidic protein in a Japanese patient with Alexander disease
• Systemic T Cell Large Granular Lymphocyte Lymphoma with Multifocal White Matter Degeneration in the Brain of a Japanese Domestic Cat
• Dielectric Properties of the Low Temperature Phase of Fe_3O_4 at a Microwave Frequency
• Possible Involvement of Long Chain Fatty Acids in the Spores of Ganoderma lucidum (Reishi Houshi) to Its Anti-tumor Activity(Pharmacology)
• Involvement of Ca^ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats
• Effects of D-Fraction, a Polysaccharide from Grifola frondosa on Tumor Growt Involve Activation of NK Cells
• Computational Analysis of Molecular Recognition in DNA Base-Sequence and Groove by Methidium Chloride Using Molecular Mechanics Calculation
• Electrophysiological Characterization of Nicotine-Induced Excitaiton of Dopaminergic Neurons in the Rat Substantia Nigra
• Commensurate-Incommensurate Phase Transition in Nearly Half-Filled Band
• Commensurate-Incommensurate Charge-Density Wave Phase Transition in One-Dimensional Electron-Phonon System. II
• Regional Cerebral Blood Flow in the Persistent Vegetative State
• Possible Involvement of P2X_7 Receptor Activation in Microglial Neuroprotection against Focal Cerebral Ischemia in Rats(Pharmacology)
• Spatiotemporal Analysis of the Molecular Interaction between PICK1 and PKC
• Is bone density in the distal femur affected by use of cement and by femoral component design in total knee arthroplasty?
• A comparison of titanium alloy orthodontic wires for surface roughness using a confocal optical microscope
• Mutational analysis of MECP2 in Japanese patients with atypical Rett syndrome
• Mutation analysis of two Japanese patients with Fanconi-Bickel syndrome
• Dynamic Photoresponsive Functions in Organized Layer Systems Comprised of Azobenzene-containing Polymers
• Role of Hydrogen Bonding in Azobenzene-Urea Assemblies. Structural Evaluations of Multilayers on Solid Substrates
• Bremazocine Recognizes the Difference in Four Amino Acid Residues to Discriminate Between a Nociceptin/Orphanin FQ Receptor and Opioid Receptors
• Pathogenesis of leukodystrophy for Krabbe disease : Molecular mechanism and clinical treatment
• Theoretical Relation between Spatial Resolution and Efficiency of Detection in Scanning Hot Electron Microscope
• Shortening of Detection Time for Observation of Hot Electron Spatial Distribution by Scanning Hot Electron Microscopy
• A comparative study of frictional resistance and surface roughness between orthodontic bracket and arch wire
• Anti-allergic Substances Contained in the Pollen of Cryptomeria japonica Possess Diverse Effects on the Degranulation of RBL-2H3 Cellse
• Reversible Photoswitching Liquid-phase Adsorption on Azobenzene Derivative-grafted Mesoporous Silica
• Transport and Recognition of Aminopeptidase-Resistant Cellobiose-Coupled Tyrosylglycylglycine by Intestinal Na^+/Glucose Cotransporter (SGLT1) : Recognition of Suger Conjugates by SGLT1 Is Much Less Restricted than Transport
• Noise Robust Speech Recognition Using F_0 Contour Information(Speech Dynamics by Ear, Eye, Mouth and Machine)
• Preparation of Nanostructured Conjugated Polymers Using Template Electrochemical Polymerization in Supercritical Fluids
• Electron Spin-Lattice Relaxation of Mn^ and Cr^ Ions in Rutile
• Electron Spin-Lattice Relaxation of Fe^ Ion in Rutile
• Electron Spin-Lattice Relaxation of Min^3+ Ion in Rutile
• Temperature Dependence of EPR of Mn^ and Cr^ in Rutile
• Structure and Characteristics of an Endo-β-1,4-glucanase, Isolated from Trametes hirsuta, with High Degradation to Crystalline Cellulose
• Phase Transitions in Two-Dimensional Classical Pseudo-Harmonic Model
• Smart Photoresponsive Polymer Systems Organized in Two Dimensions
• Elucidation of the Molecular Mechanism and Exploration of Novel Therapeutics for Spinocerebellar Ataxia Caused by Mutant Protein Kinase Cγ
• Congo Red, an Amyloid-Inhibiting Compound, Alleviates Various Types of Cellular Dysfunction Triggered by Mutant Protein Kinase Cγ That Causes Spinocerebellar Ataxia Type 14 (SCA14) by Inhibiting Oligomerization and Aggregation
• Endomorphin-1 Discriminates the μ-Opioid Receptor From the δ-and κ-Opioid Receptors by Recognizing the Difference in Multiple Regions
• Surface-mediated photoalignment of organic/inorganic nanohybrids(Global Innovation in Advanced Ceramics)
• In situ Polymerization of Liquid Crystalline Monomers within Photoaligned Mesoporous Silica Thin Film
• Commensurate-Incommensurate Phase Transition in a Pseudo-Harmonic Model : Kink Lattice
• Commensurate-Incommensurate Phase Transition in Quasi One-Dimensional Electron-Phonon System : Nearly Half-Filled Band
• Commensurate-Incommensurate Charge-Density Wave Phase Transition in One-Dimensional Electron-Phonon System
• Commensurate-Incommensurate Transition in Sine-Gordon Fields
• Possible Involvement of Descending Serotonergic Systems in Antinociception by Centrally Administered Elcatonin in Mice
• Recent advances in hydrogels in terms of fast stimuli responsiveness and superior mechanical performance
• Spontaneous Bilateral Intracerebral Hemorrhage Occurring Simultaneously : Case Report
• Exact Relation between the Sine-Gordon System and the Coulomb Gas System
• Commensurate-Incommensurate Cross-Over in the One-Dimensional Quantum Sine-Gordon System (g^2=4π)
• Note on Critical Exponents for Sinusoidal Spin Arrangements
• Commensurate-Incommensurate Transition in a Two Dimensional Classical Sine-Gordon System
• Note on the Ground State of the Peierls-Frohlich System : Nearly 1/3 Filled Band
• First Order Melting Transition in the Incommensurate Phase
• Light-directed Dynamic Structure Formation and Alignment in Photoresponsive Thin Films
• CONCENTRATION DISTRIBUTION OF SOIL PARTICLES AND POLLUTANTS IN THE MARINE ATMOSPHERE AND THEIR TRANSPORT TO THE OCEAN
• Clinical aspects and adrenal functions in eleven Japanese children with X-linked adrenoleukodystrophy
• Depth Distribution of Characteristic X-rays in EPMA Alloy Targets : I. Angular Distribution and f(x)-Curves of Fe K X-rays in Fe-Al Alloy Targets
• 92. The effect of the repeated electrical shocks to dogs.
• Elucidation of the Molecular Mechanism and Exploration of Novel Therapeutics for Spinocerebellar Ataxia Caused by Mutant Protein Kinase Cγ
• CONCENTRATIONS OF SULFUR COMPOUNDS (MSA, SO_2 AND NSS-SO_4^) IN THE MARINE ATMOSPHERE, AND ESTIMATION OF BIOGENIC SULFUR EMISSION FROM THE SEA
• Charge Transport Anisotropy due to Interfacial Molecular Orientation in Polymeric Transistors with Controlled In-Plane Chain Orientation
• Assessment of Workplace Air Concentrations of Indium Dust in an Indium-recycling Plant
• Chaos in One-Dimensional Dynamical Systems (Random Systems and Dynamical Systems)
• In Process Control of Weld Pool using Weaving Control in Switch Back Welding
• A versatile photochemical procedure to introduce a photoreactive molecular layer onto a polyimide film for liquid crystal alignment
• SLC2A1 gene analysis of Japanese patients with glucose transporter 1 deficiency syndrome
• Mucolipidosis II and III alpha/beta : mutation analysis of 40 Japanese patients showed genotype-phenotype correlation
• Feasibility of unmanipulated haploidentical stem cell transplantation using standard GVHD prophylaxis for HLA-homozygous patients
• Leukodystrophies (International Review of Child Neurology Series)
• Effectiveness of Lanthanum Carbonate Treatment Used in Combination with Other Phosphate Binders in Peritoneal Dialysis Patients
• Long-Term Exposure of RN46A Cells Expressing Serotonin Transporter (SERT) to a cAMP Analog Up-regulates SERT Activity and Is Accompanied by Neural Differentiation of the Cells
• Clinicogenetical features of a Japanese patient with giant axonal neuropathy
• Two-Dimensional Manipulation of Poly(3-dodecylthiophene) using Light-Driven Instant Mass Migration as a Molecular Conveyer
• Long-term Sequential Changes of Radiation Proctitis and Angiopathy in Rats
• Effects of the Chemical Chaperone 4-Phenylbutylate on the Function of the Serotonin Transporter (SERT) Expressed in COS-7 Cells
• Antiepileptic Effects of Single and Repeated Oral Administrations of S-312-d, a Novel Calcium Channel Antagonist, on Tonic Convulsions in Spontaneously Epileptic Rats
• Shortening of Detection Time for Observation of Hot Electron Spatial Distribution by Scanning Hot Electron Microscopy
• Long-Term Exposure of RN46A Cells Expressing Serotonin Transporter (SERT) to a cAMP Analog Up-regulates SERT Activity and Is Accompanied by Neural Differentiation of the Cells
• Pre-dinner administration increases the efficacy of proton pump inhibitors on refractory GERD symptoms in connective tissue disease patients
• Occupational Exposure to N,N-Dimethylformamide in the Summer and Winter
• Difference in mitochondrial gene expression in granulosa cells between recombinant FSH and hMG cycles under in vitro fertilization and transfer

もっと見る 閉じる

スポンサーリンク