Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 683
Filter
1.
Article in Chinese | WPRIM | ID: wpr-928088

ABSTRACT

In this study, we analyzed the composition and content of 25 free amino acids in 32 batches of different forms of Cervi Cornu Pantotrichum(CCP; one-branched, two-branched, and three-branched) from 15 producing areas. The clustering analysis and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed based on the content of 25 free amino acids. Potential differential metabolites were identified based on VIP value. The results showed that there were 25 free amino acids in CCP, and the average content of essential, non-essential, and total amino acids was 6.13, 32.99, and 39.12 mg·g~(-1), respectively. The clustering analysis and OPLS-DA demonstrated that 25 free amino acids had different content among the three forms of CCP, of which two-branched CCP samples were separately gathered into a group. Five differential components, including glutamic acid, tryptophan, ornithine, γ-aminobutyric acid, and hydroxylysine, were screened out as potential quality markers for the identification of different forms of CCP. This study provides a theoretical basis for the quality evaluation, processing, and utilization of different forms of CCP.


Subject(s)
Amino Acids/analysis , Animals , Cornus , Deer , Gastropoda , Glutamic Acid
2.
Medicina (B.Aires) ; 81(5): 774-779, oct. 2021. graf
Article in Spanish | LILACS | ID: biblio-1351050

ABSTRACT

Resumen El objetivo del trabajo fue evaluar la asociación entre el nivel de glutamato en el líquido cefalorraquídeo (LCR) al inicio de la enfermedad y la progresión de la enfermedad durante el seguimiento en una cohorte de pacientes con esclerosis múltiple (EM). Se determinaron niveles de glutamato (Glu) en LCR al inicio de la enfermedad. Se realizó una resonancia basal y durante el seguimiento cada 12 meses con el objeto de determinar el porcentaje de cambio de volumen cerebral (PCVC), grosor cortical (GC) y volumen le sional cerebral en secuencia T2 (VLT2). Los predictores primarios de interés fueron los niveles basales de Glu en LCR, PCVC Y GC, así como la progresión clínica de la enfermedad [medida por Expanded Disability Status Scale (EDSS) y tasa anual de recaídas]. Un total de 26 pacientes fueron incluidos. La concentración media de Glu fue de 5.3 ± 0.4 μM/l. Se encontró una asociación significativa entre concentraciones basales elevadas de Glu y la progresión del EDSS (b = 1.06, IC 95% 0.47-1.66, p = 0.003), así como también el PCVC (b = -0.71, IC 95% -0.56-1.38, p = 0.002) y CG (b = -0.15, IC 95% -0.06-0.33, p = 0.01). No se encontró asociación entre los niveles de Glu y la tasa anual de recaídas como tampoco el VLT2 (b = 0.08, IC 95% -0.11-0.43, p = 0.11 y b = 195, IC -39-330, p = 0.22, respectivamente). Los niveles aumentados de Glu se asociaron con un mayor cambio en el PCVC y progresión del EDSS durante el seguimiento.


Abstract. The objective of this study was to evaluate the association between glutamate (Glu) levels in cerebrospinal fluid (CSF) at disease onset and disease progression during follow up in a cohort of multiple sclerosis (MS) patients. Glu level was measured at disease onset (first relapse). MRI was obtained at baseline and follow-up (every 12 months) to determine the percent of brain volume change (PBVC), cortical thickness (CT), and T2 lesion volume (T2LV). The primary predictors of interest were baseline CSF Glu levels, PBVC and CT, as well as clinical disease progression [measured by Expanded Disability Status Scale (EDSS) and annualized relapse rate] during follow-up. A total of 26 MS patients were included. Mean concentration of Glu in CSF at diagnosis was 5.3 ± 0.4 μM/l. A significant association was observed between higher baseline levels of Glu and an increase in EDSS during follow up (b = 1.06, 95%CI 0.47-1.66, p = 0.003) as well as PBVC (b = -0.71 95%CI -0.56-1.38, p = 0.002) and CT (b = -0.15, 95%CI -0.06-0.33, p = 0.01). We did not observe an association between baseline Glu levels and relapse rate or T2LV during follow-up (b = 0.08, 95%CI -0.11-0.43, p = 0.11 and b = 195, 95%CI -39-330, p = 0.22, respectively). Higher Glu concentrations at disease onset were associated with an increase in PBVC and EDSS progression during follow-up in MS patients.


Subject(s)
Humans , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis/diagnostic imaging , Prognosis , Glutamic Acid
3.
Article in English | WPRIM | ID: wpr-922588

ABSTRACT

OBJECTIVES@#To explore the metabolite characteristics in medial prefrontal cortex (mPFC) by @*METHODS@#A total of 46 patients with the first-episode schizophrenia (FES), 49 people with clinical high risk (CHR), 61 people with genetic high risk (GHR), and 58 healthy controls (HC) were enrolled. The levels of N-acetylaspartylglutamate+N-acetylaspartate (tNAA), choline-containing compounds (Cho) and myo-inositol (MI), glutamate+glutamine (Glx) in medial prefrontal cortex were measured by single-voxel @*RESULTS@#There were significant differences in Glx, tNAA, and MI concentrations among 4 groups (all @*CONCLUSIONS@#The decreased levels of MI and Glx in the FES patients suggest that there may be glial functional damage and glutamatergic transmitter dysfunction in the early stage of the disease. The compensatory increase of metabolites may be a protective factor for schizophrenia in the genetic individuals.


Subject(s)
Aspartic Acid , Glutamic Acid , Glutamine , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Proton Magnetic Resonance Spectroscopy , Schizophrenia
4.
Prensa méd. argent ; 106(9): 513-519, 20200000. tab, fig
Article in Spanish | LILACS, BINACIS | ID: biblio-1362771

ABSTRACT

Introducción: El síndrome del hombre rígido representa una rara enfermedad neuromuscular caracterizada por rigidez muscular progresiva y espasmos musculares dolorosos que afecta a 1 persona por cada millón de habitantes por año en el mundo. En la mayoría de los pacientes se encuentran niveles elevados de anticuerpos descarboxilasa del ácido glutámico. En Colombia solo se han publicado alrededor de 3 casos, lo que motiva la presentación de un nuevo informe que aporte a la discusión actual en el campo de la neurología clínica. Caso clínico: Paciente de sexo femenino de 35 años con cuadro clínico progresivo de varios años, caracterizado por contracciones paroxísticas dolorosas, parestesias y pérdida de fuerza. Se documentó la presencia de anticuerpos anti-GAD compatibles con el síndrome del hombre rígido. Tras un tratamiento integral, que incluyó la infusión farmacológicamente intratecal con baclofeno, se obtuvo mejoría clínica en el índice de Barthel. Conclusiones: El síndrome del hombre rígido es una condición infradiagnosticada que se asocia a un deterioro de la calidad de vida de quienes lo padecen.


Introduction: Stiff man syndrome represents a rare neuromuscular disease characterized by progressive muscle rigidity and painful muscle spasms that affects 1 person for every million habitants per year in the world. High levels of glutamic acid antibodies decarboxylase are found in most patients. In Colombia, only around 3 cases have been published, which motivates the presentation of a new report that contributes to the current discussion in the field of clinical neurology. Clinical Case: 35-year-old female patient with a progressive clinical picture of several years, characterized by painful paroxysmal contractions, paresthesias and loss of strength. The presence of anti-GAD antibodies was documented, compatible with Stiff man syndrome. After comprehensive treatment, which included pharmacologically intrathecal infusion with baclofen, clinical improvement was obtained in the Barthel index. Conclusions: Stiff man syndrome is an underdiagnosed condition which is associated with a deterioration in the quality of life for those who suffer from it.


Subject(s)
Humans , Female , Adult , Paresthesia/diagnosis , Quality of Life , Baclofen/therapeutic use , Stiff-Person Syndrome/diagnosis , Glutamic Acid , Neuromuscular Manifestations , Diagnosis, Differential , Muscle Rigidity/diagnosis
5.
Chinese Journal of Biotechnology ; (12): 820-828, 2020.
Article in Chinese | WPRIM | ID: wpr-826894

ABSTRACT

Corynebacterium glutamicum, an important microorganism to produce amino acids and organic acids, has been widely applied in food and medicine fields. Therefore, using editing tools to study the function of unknown genes in C. glutamicum has great significance for systematic development of industrial strain with efficient and novel production capability. Recently, gene editing has been greatly developed. Traditional gene editing based on homologous recombination and gene editing mediated by nuclease are successfully applied in C. glutamicum. Among these, the CRISPR system has been developed to be a main tool used for gene knockout of C. glutamicum due to its advantages of efficiency, simplicity and good target specificity. However, more efficient and reliable knockout system is still urgently demanded, to help develop high-performing strains in industrial application.


Subject(s)
CRISPR-Cas Systems , Clustered Regularly Interspaced Short Palindromic Repeats , Corynebacterium glutamicum , Genetics , Gene Editing , Glutamic Acid , Industrial Microbiology
6.
Article in English | WPRIM | ID: wpr-787134

ABSTRACT

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.


Subject(s)
Amino Acids , Binding Sites , Calcium , Cytosol , Glutamic Acid , Myocytes, Smooth Muscle , Permeability , Polyamines , Receptors, Muscarinic , Spermine , Transient Receptor Potential Channels
7.
Chinese Journal of Biotechnology ; (12): 2113-2125, 2020.
Article in Chinese | WPRIM | ID: wpr-878471

ABSTRACT

Glutamic acid is an important amino acid with wide range of applications and huge market demand. Therefore, by performing transcriptome sequencing and re-sequencing analysis on Corynebacterium glutamicum E01 and high glutamate-producing strain C. glutamicum G01, we identified and selected genes with significant differences in transcription and gene levels in the central metabolic pathway that may have greatly influenced glutamate synthesis and further increased glutamic acid yield. The oxaloacetate node and α-ketoglutarate node play an important role in glutamate synthesis. The oxaloacetate node and α-ketoglutarate node were studied to explore effect on glutamate production. Based on the integrated strain constructed from the above experimental results, the growth rate in a 5-L fermenter was slightly lower than that of the original strain, but the glutamic acid yield after 48 h reached (136.1±5.53) g/L, higher than the original strain (93.53±4.52) g/L, an increase by 45.5%; sugar-acid conversion rate reached 58.9%, an increase of 13.7% compared to 45.2% of the original strain. The application of the above experimental strategy improved the glutamic acid yield and the sugar-acid conversion rate, and provided a theoretical basis for the metabolic engineering of Corynebacterium glutamicum.


Subject(s)
Citric Acid Cycle , Corynebacterium glutamicum/metabolism , Glutamic Acid/metabolism , Metabolic Engineering , Metabolic Networks and Pathways/genetics
8.
Rev. bras. cancerol ; 66(1)20200129.
Article in English | LILACS | ID: biblio-1049323

ABSTRACT

Introduction: Three vanadium complexes with orotic and glutamic acids, in their anion forms, were prepared and their in vitro cytotoxicity toward human lung fibroblasts (MRC-5), human hepatocellular carcinoma (HepG2) and human colorectal adenocarcinoma (Caco-2) are reported. Objective: Describe the synthesis and characterization of new vanadium complexes with orotic and glutamic acids, and test its antitumor activity against HepG2 and Caco-2. Method: The complexes were formulated as VO (oro), VO (α-glu) and VO (γ-glu) based on chemical, thermogravimetric analyses and infrared spectra. Results: Resazurin assay demonstrates its cytotoxicity against the HepG2 and Caco-2 cell lines with the IC50 ranging from 7.90 to 44.56 µmol.L-1. The cytotoxicity profiles indicate that the tumoral lines show more activity than the cells MRC-5, with selectivity indexes ranging from 1.58 to 8.96. Conclusion: The three complexes had better in vitro activity than cisplatin for both normal and cancer cell lines. The IC50 values are two to six times better for the cancer cell ines and five to seven times better for the normal cell lines. This study indicates that the complexes obtained are promising candidates for antitumor drugs.


Introdução: Foram preparados três complexos de vanádio com ácidos orótico e glutâmico, em suas formas aniônicas, e foi testada sua citotoxicidade in vitro para fibroblastos pulmonares humanos (MRC-5), carcinoma hepatocelular humano (HepG2) e adenocarcinoma colorretal humano (Caco-2). Objetivo: Descrever a síntese e caracterização de novos complexos de vanádio com ácidos orótico e glutâmico e testar sua atividade antitumoral contra HepG2 e Caco-2. Método: Os complexos foram formulados como VO (oro), VO (α-glu) e VO (γ-glu) com base em análises químicas, termogravimétricas e espectros no infravermelho. Resultados: O ensaio de resazurina demonstrou sua citotoxicidade contra as linhagens celulares HepG2 e Caco-2 com o IC50 variando de 7,90 a 44,56 µmol.L-1. Os perfis de citotoxicidade indicam que as linhas tumorais apresentam maior atividade que as células MRC-5, com índices de seletividade variando de 1,58 a 8,96. Conclusão: Os três complexos tiveram melhor atividade in vitro do que a cisplatina, tanto para linhagens celulares normais como cancerosas. Os valores de IC50 são de duas a seis vezes melhores para as linhagens celulares cancerosas e de cinco a sete vezes melhores para as linhagens celulares normais. Este estudo indica que os complexos obtidos são promissores candidatos a fármacos antitumorais.


Introducción: Tres complejos de vanadio con ácidos orótico y glutámico, en sus formas aniónicas, fueram preparados. Su citotoxicidad in vitro hacia los fibroblastos pulmonares humanos (MRC-5), el carcinoma hepatocelular humano (HepG2) y el adenocarcinoma colorrectal humano (Caco-2) son reportados. Objetivo: Los principales objetivos de este trabajo son describir la síntesis y caracterización de nuevos complejos de vanadio con ácidos orótico y glutámico y probar su actividad antitumoral contra el HepG2 y el Caco-2. Método: Los complejos fueron formulados como VO (oro), VO (α-glu) y VO (γ-glu) basados en análisis químicos, termogravimétricos y espectros infrarrojos. El ensayo de resazurina demuestra su citotoxicidad contra las líneas celulares HepG2 y Caco-2 con el IC50 que van de 7,90 a 44,56 µmol.L-1. Los perfiles de citotoxicidad indican que las líneas tumorales presentan mayor actividad que los MRC-5, con índices de selectividad que van de 1,58 a 8,96. Conclusión: Los tres complejos tuvieron mejor actividad in vitro que el cisplatino, tanto para líneas celulares normales como para líneas celulares cancerosas. Los valores del IC50 son de dos a seis veces mejores para las líneas celulares de cáncer y de cinco a siete veces mejores para las líneas celulares normales. Este estudio indica que los complejos obtenidos son candidatos prometedores para fármacos antitumorales.


Subject(s)
Humans , Orotic Acid/pharmacology , Vanadium Compounds/pharmacology , Glutamic Acid/pharmacology , Cell Line, Tumor/drug effects , In Vitro Techniques , Drug Screening Assays, Antitumor , Colorectal Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Carcinoma, Hepatocellular/drug therapy , Cancer-Associated Fibroblasts/drug effects , Lung Neoplasms/drug therapy , Antineoplastic Agents/pharmacology
9.
Biol. Res ; 53: 36, 2020. tab, graf
Article in English | LILACS | ID: biblio-1131882

ABSTRACT

BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.


Subject(s)
Animals , Rats , Thalamus/metabolism , Wounds and Injuries/physiopathology , Neurotransmitter Agents/metabolism , Neuralgia , Thalamus/physiopathology , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Glutamic Acid/metabolism , Constriction , Hyperalgesia
10.
Rev. cuba. invest. bioméd ; 38(1): e164, Jan.-Mar. 2019.
Article in English | LILACS, CUMED | ID: biblio-1093384

ABSTRACT

Introduction: The etiology of autoimmune diseases is still unknown, but different causes arise. Objective: To describe the role of hormones, diet, stress and infections in the etiology of autoimmune diseases. Methods: A bibliographic review was made using the Google Scholar and articles of free access in the Pubmed and Scielo database from 2015 to 2019. The search terms were used according to the DeCS and MeSH descriptors. Development: It is well known that female hormones increase the risk of autoimmune diseases. Stress can maintain low-grade chronic inflammatory responses that cause tissue damage, initiating or aggravating the clinical manifestations of autoimmunity. An adequate diet allows the guests of the intestinal microbiota to maintain the homeostasis of the immune system. Today, glutamate is used as a flavor enhancer, especially in developed countries. Perhaps it is one of the causes of the higher incidence of autoimmune diseases in these regions. Conclusions: Autoimmune diseases are more frequent in women. Adequate nutrition allows the gut microbiota not to be altered and to maintain immunological homeostasis. Infections and stress situations can trigger or exacerbate the clinical manifestations of autoimmunity(AU)


Subject(s)
Humans , Female , Autoimmune Diseases , Autoimmunity , Glutamic Acid/genetics , Nutritional Sciences
11.
Article in English | WPRIM | ID: wpr-741711

ABSTRACT

BACKGROUND/OBJECTIVES: Oxidative stress is a major effector of various diseases; accordingly, antioxidants are frequently ingested in order to prevent or alleviate disease symptoms. Kimchi contains various natural antioxidants, and it is known that the functional activity varies depending on the ingredients and fermentation state. Black raspberries (BR) contain various bioactive compounds with antioxidant effects. This study investigated the antioxidant and liver-protection effects of kimchi supplemented with black raspberry juice powder (BJP). MATERIALS/METHODS: BJP-added kimchi (BAK; at 0.5%, 1%, and 2% concentrations of BJP) and control (without BJP) were prepared and fermented at 4℃ for 4 weeks. Changes in the antioxidant effects of BAK during fermentation were investigated. In addition, the protective activity of BAK against oxidative stress was investigated in a liver cirrhosis-induced animal model in vivo. RESULTS: BAK groups showed the acidity and pH of optimally ripened (OR) kimchi at 2 weeks of fermentation along with the highest lactic acid bacterial counts. Additionally, BAK groups displayed a higher content of phenolic compounds and elevated antioxidant activities relative to the control, with the highest antioxidant effect observed at 2 weeks of fermentation of OR 1% BAK. After feeding the OR 1% BAK to thioacetamide-induced liver cirrhosis rats, we observed decreased glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities and elevated superoxide dismutase activity. CONCLUSIONS: These findings showed that the antioxidant effects of OR BAK and feeding of OR 1% BAK resulted in liver-protective effects against oxidative stress.


Subject(s)
Animals , Antioxidants , Bacterial Load , Fermentation , Glutamic Acid , Hydrogen-Ion Concentration , Lactic Acid , Liver Cirrhosis , Liver , Models, Animal , Oxaloacetic Acid , Oxidative Stress , Phenol , Pyruvic Acid , Rats , Rubus , Superoxide Dismutase
12.
Article in English | WPRIM | ID: wpr-759513

ABSTRACT

BACKGROUND: Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms. METHODS: Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed. RESULTS: Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats. CONCLUSIONS: This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.


Subject(s)
Adult , Animals , Autistic Disorder , Child , Dexmedetomidine , Electroencephalography , Female , gamma-Aminobutyric Acid , Gene Expression , Glutamic Acid , Humans , Infant, Newborn , Male , Models, Animal , N-Methylaspartate , Neurodevelopmental Disorders , Propofol , Rats , Rats, Sprague-Dawley , Receptors, GABA-A , Receptors, Glutamate , Reflex, Righting , Valproic Acid
13.
Article in English | WPRIM | ID: wpr-765337

ABSTRACT

OBJECTIVE: Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson’s disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum. METHODS: Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed. RESULTS: Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category. CONCLUSION: Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.


Subject(s)
Animals , Basal Ganglia , Chromatography, Liquid , Deep Brain Stimulation , Entopeduncular Nucleus , Globus Pallidus , Glutamates , Glutamic Acid , Humans , Microdialysis , Neurotransmitter Agents , Oxidopamine , Parkinson Disease , Rats , Substantia Nigra , Thalamus , Tyrosine 3-Monooxygenase
14.
Article in English | WPRIM | ID: wpr-764307

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the third most common cause of cancer-related death worldwide. HCC is caused by infection of hepatitis B/C virus and liver dysfunctions, such as alcoholic liver disease, nonalcoholic fatty liver disease, and cirrhosis. Amino acids are organic substances containing amine and carboxylic acid functional groups. There are over 700 kinds of amino acids in nature, but only about 20 of them are used to synthesize proteins in cells. Liver is an important organ for protein synthesis, degradation and detoxification as well as amino acid metabolism. In the liver, there are abundant non-essential amino acids, such as alanine, aspartate, glutamate, glycine, and serine and essential amino acids, such as histidine and threonine. These amino acids are involved in various cellular metabolisms, the synthesis of lipids and nucleotides as well as detoxification reactions. Understanding the role of amino acids in the pathogenesis of liver and the effects of amino acid intake on liver disease can be a promising strategy for the prevention and treatment of liver disease. In this review, we describe the biochemical properties and functions of amino acids and to review how they have been applied to treatment of liver diseases.


Subject(s)
Alanine , Amino Acids , Amino Acids, Essential , Aspartic Acid , Carcinoma, Hepatocellular , Fibrosis , Glutamic Acid , Glycine , Hepatitis , Histidine , Liver Diseases , Liver Diseases, Alcoholic , Liver , Metabolism , Non-alcoholic Fatty Liver Disease , Nucleotides , Serine , Therapeutic Uses , Threonine
15.
Experimental Neurobiology ; : 495-503, 2019.
Article in English | WPRIM | ID: wpr-763778

ABSTRACT

Memantine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNF α)genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.


Subject(s)
Acoustics , Animals , Auditory Cortex , Brain Stem , Evoked Potentials, Auditory, Brain Stem , Genes, Immediate-Early , Glutamic Acid , Immunohistochemistry , Integrin alpha2 , Memantine , Models, Animal , N-Methylaspartate , Neurons , Noise , Prepulse Inhibition , Rats , Reflex, Startle , Tinnitus , Tumor Necrosis Factor-alpha
16.
Article | WPRIM | ID: wpr-763548

ABSTRACT

OBJECTIVE: Until recently, riluzole was the only drug licensed for amyotrophic lateral sclerosis (ALS). In spite of its efficacy, the mechanism of action remains elusive, and both blocking of glutamate release and antioxidant properties have been postulated. Here we characterized human SH-SY5Y neuroblastoma cell lines, taking advantage of their insensitivity to excitotoxic insults, in order to selectively assess the presence of a direct antioxidant effect of riluzole. METHODS: SH-SY5Y cells, either parental or overexpressing the G93A SOD1 mutation, were exposed for 24 hours to the selected stimuli. RESULTS: Riluzole (1–10 μM) was able to counteract the effects of H₂O₂ exposure (200 μM/24 hr), limiting both cell death and whole-cell reactive oxygen species (ROS) increase. The same experiments were repeated using SH-SY5Y cells carrying the familial ALS-related G93A-SOD1 mutation and constitutively expressing two-fold increased whole-cell ROS levels with respect to wild-type cells: riluzole was ineffective in this paradigm. Analogously, riluzole was ineffective in preventing cell death induced by exposing SH-SY5Y cells to 3-morpholino-sydnonimine (SIN-1, 1.5 mM/24 hr), a reactive nitrogen species (RNS) donor. CONCLUSION: Our data support a direct antioxidant action of riluzole. Furthermore, the lack of efficacy of riluzole observed in the SOD1 cell model mirrors the lack of efficacy already demonstrated in cognate mouse models of ALS, plausibly reflecting differences in the underlying pathogenic mechanisms. Finally, riluzole inefficacy against nitrosative stress might support the idea that a combined therapeutic intervention may result more effective in ALS patients, as in the case of co-administration of edaravone, a drug known to reduce RNS.


Subject(s)
Amyotrophic Lateral Sclerosis , Animals , Antioxidants , Cell Death , Cell Line , Endophenotypes , Glutamic Acid , Humans , Mice , Neuroblastoma , Parents , Reactive Nitrogen Species , Reactive Oxygen Species , Riluzole , Tissue Donors
17.
Article in English | WPRIM | ID: wpr-763542

ABSTRACT

Panic disorder (PD) being one of the most intensively investigated anxiety disorders is considered a heterogeneous psychiatric disease which has difficulties with early diagnosis. The disorder is recurrent and usually associated with low remission rates and high rates of relapse which may exacerbated social and quality of life, causes unnecessary cost and increased risk for complication and suicide. Current pharmacotherapy for PD are available but these drugs have slow therapeutic onset, several side effects and most patients do not fully respond to these standard pharmacological treatments. Ongoing investigations indicate the need for new and promising agents for the treatment of PD. This article will cover the importance of immediate and proper treatment, the gap in the current management of PD with special emphasis on pharmacotherapy, and evidence regarding the novel anti-panic drugs including the drugs in developments such as metabotropic glutamate (mGlu 2/3) agonist and levetiracetam. Preliminary results suggest the anti-panic properties and the efficacy of duloxetine, reboxetine, mirtazapine, nefazodone, risperidone and inositol as a monotherapy drug. Apart for their effectiveness, the aforementioned compounds were generally well tolerated compared to the standard available pharmacotherapy drugs, indicating their potential therapeutic usefulness for ambivalent and hypervigilance patient. Further strong clinical trials will provide an ample support to these novel compounds as an alternative monotherapy for PD treatment-resistant patient.


Subject(s)
Antidepressive Agents , Antipsychotic Agents , Anxiety , Anxiety Disorders , Drug Therapy , Duloxetine Hydrochloride , Early Diagnosis , Glutamic Acid , Humans , Inositol , Panic Disorder , Panic , Quality of Life , Recurrence , Risperidone , Suicide
18.
Article in English | WPRIM | ID: wpr-763125

ABSTRACT

PURPOSE: Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel nuclear receptor (NR) co-regulator, is highly expressed in breast cancer. We investigated its expression in breast cancer subtypes, in comparison with other breast markers as well as cancers from different sites. Its prognostic relevance with different subtypes and other NR expression was also examined in breast cancers. MATERIALS AND METHODS: Immunohistochemical analysis was performed on totally 1,944 cancers from six different organs. RESULTS: PELP1 expression rate was the highest in breast cancers (70.5%) among different cancers. Compared to GATA3, mammaglobin and gross cystic disease fluid protein 15, PELP1 was less sensitive than GATA3 for luminal cancers, but was the most sensitive for non-luminal cancers. PELP1 has low expression rate (<20%) in colorectal cancers, gastric cancers and renal cell carcinomas, but higher in lung cancers (49.1%) and ovarian cancers (42.3%). In breast cancer, PELP1 expression was an independent adverse prognostic factor for non-luminal cancers (disease-free survival [DFS]: hazard ratio [HR], 1.403; p=0.012 and breast cancer specific survival [BCSS]: HR, 1.443; p=0.015). Interestingly, its expression affected the prognostication of androgen receptor (AR). AR(pos)PELP1(lo) luminal cancer showed the best DFS (log-rank=8.563, p=0.036) while AR(neg)PELP1(hi) non-luminal cancers showed the worst DFS (log-rank=9.536, p=0.023). CONCLUSION: PELP1 is a sensitive marker for breast cancer, particularly non-luminal cases. However, its considerable expression in lung and ovarian cancers may limit its utility in differential diagnosis in some scenarios. PELP1 expression was associated with poor outcome in non-luminal cancers and modified the prognostic effects of AR, suggesting the potential significance of NR co-regulator in prognostication.


Subject(s)
Breast Neoplasms , Breast , Carcinoma, Renal Cell , Colorectal Neoplasms , Diagnosis, Differential , Glutamic Acid , Immunohistochemistry , Lung , Lung Neoplasms , Ovarian Neoplasms , Phenobarbital , Prognosis , Proline , Receptors, Androgen , Stomach Neoplasms
19.
Chinese Journal of Biotechnology ; (12): 636-646, 2019.
Article in Chinese | WPRIM | ID: wpr-771345

ABSTRACT

Glutamate decarboxylase, a unique pyridoxal 5'-phosphate-dependent enzyme, catalyzes α-decarboxylation of L-glutamate to γ-aminobutyrate. However, glutamate decarboxylase from different sources has the common problem of poor thermostability that affects its application in industry. In this study, proline was introduced at 13 different positions in glutamate decarboxylase by using the design strategy of homologous sequence alignment between Thermococcus kodakarensis and Lactobacillus brevis CGMCC No.1306. A mutant enzyme G364P with higher thermostability was obtained. Compared to the wild type, thermostability of the mutant G364P was significantly improved, the half-life time (t1/2) at 55 °C and the semi-inactivation temperature (T₅₀ ¹⁵) of the mutant G364P increased 19.4 min and 5.3 °C, respectively, while kcat/Km of the mutant enzyme remained nearly unchanged. Further analysis of their thermostability by molecular dynamics simulations were performed. The root mean square deviation of G364P and root mean square fluctuation in the loop region including G364 were lower than the wild type at 313 K for 10 ns, and G364P increased one hydrophobic interaction in the loop region. It proves that mutation of flexible 364-Gly to rigid proline endows glutamate decarboxylase with enhanced thermostability.


Subject(s)
Glutamate Decarboxylase , Glutamic Acid , Lactobacillus brevis , Molecular Dynamics Simulation , Proline
20.
Neuroscience Bulletin ; (6): 447-460, 2019.
Article in English | WPRIM | ID: wpr-775438

ABSTRACT

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR-vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR-vlOFC pathway in mice. We determined that the POR-vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR-vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.


Subject(s)
Animals , Glutamic Acid , Physiology , Male , Mental Recall , Physiology , Mice, Inbred C57BL , Neural Pathways , Cell Biology , Physiology , Neuroanatomical Tract-Tracing Techniques , Neurons , Physiology , Prefrontal Cortex , Cell Biology , Physiology , Spatial Memory , Physiology , Temporal Lobe , Cell Biology , Physiology
SELECTION OF CITATIONS
SEARCH DETAIL