RESUMEN
Aminoethylsulfonate (taurine) is widespread in the environment and highly abundant in the human body. Taurine and other aliphatic sulfonates serve as sulfur sources for diverse aerobic bacteria, which carry out cleavage of the inert sulfonate C-S bond through various O2-dependent mechanisms. Taurine also serves as a sulfur source for certain strict anaerobic fermenting bacteria. However, the mechanism of C-S cleavage by these bacteria has long been a mystery. Here we report the biochemical characterization of an anaerobic pathway for taurine sulfur assimilation in a strain of Clostridium butyricum from the human gut. In this pathway, taurine is first converted to hydroxyethylsulfonate (isethionate), followed by C-S cleavage by the O2-sensitive isethionate sulfo-lyase IseG, recently identified in sulfate- and sulfite-reducing bacteria. Homologs of the enzymes described in this study have a sporadic distribution in diverse strict and facultative anaerobic bacteria, from both the environment and the taurine-rich human gut, and may enable sulfonate sulfur acquisition in certain nutrient limiting conditions.
Asunto(s)
Proteínas Bacterianas , Clostridium butyricum , Microbioma Gastrointestinal , Intestinos/microbiología , Familia de Multigenes , Taurina , Anaerobiosis , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Clostridium butyricum/genética , Clostridium butyricum/metabolismo , Humanos , Ácido Isetiónico/metabolismo , Sulfatos/metabolismo , Taurina/biosíntesis , Taurina/genéticaRESUMEN
Sarcopenia that occurs with advancing age is characterized by a gradual loss of muscle protein component due to the activation of catabolic pathways, increased level of inflammation, and mitochondrial dysfunction. Experimental evidence demonstrates that several physio-pathological processes involved in the onset of sarcopenia may be counteracted by the intake of specific amino acids or antioxidant molecules, suggesting that diet may represent an effective strategy for improving the anabolic response of muscle during aging. The non-essential amino acid taurine is highly expressed in several mammalian tissues, including skeletal muscle where it is involved in the ion channel regulation, in the modulation of intracellular calcium concentration, and where it plays an important role as an antioxidant and anti-inflammatory factor. Here, with the purpose to reproduce the chronic low-grade inflammation characteristics of senescent muscle in an in vitro system, we exploited the role of Tumor Necrosis Factor α (TNF) and we analyzed the effect of taurine in the modulation of different signaling pathways known to be dysregulated in sarcopenia. We demonstrated that the administration of high levels of taurine in myogenic L6 cells stimulates the differentiation process by downregulating the expression of molecules involved in inflammatory pathways and modulating processes such as autophagy and apoptosis. Although further studies are currently ongoing in our laboratory to better elucidate the molecular mechanisms responsible for the positive effect of taurine on myogenic differentiation, this study suggests that taurine supplementation may represent a strategy to delay the loss of mass and functionality characteristic of senescent muscles.
Asunto(s)
Inflamación/genética , Sarcopenia/genética , Taurina/genética , Factor de Necrosis Tumoral alfa/genética , Envejecimiento/genética , Envejecimiento/patología , Aminoácidos/genética , Animales , Antioxidantes/metabolismo , Autofagia/genética , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Inflamación/metabolismo , Inflamación/patología , Metabolismo/genética , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Ratas , Sarcopenia/patología , Transducción de Señal/genética , Taurina/metabolismoRESUMEN
The UAG termination codon is generally recognized as the least efficient and least frequently used of the three universal stop codons. This is substantiated by numerous studies in an array of organisms. We present here evidence of a translational readthrough of a mutant nonsense UAG codon in the transcript from the cysteine sulfinic acid decarboxylase (csad) gene (ENSDARG00000026348) in zebrafish. The csad gene encodes the terminal enzyme in the taurine biosynthetic pathway. Taurine is a critical amino acid for all animals, playing several essential roles throughout the body, including modulation of the immune system. The sa9430 zebrafish strain (ZDB-ALT-130411-5055) has a point mutation leading to a premature stop codon (UAG) 20 amino acids 5' of the normal stop codon, UGA. Data from immunoblotting, enzyme activity assays, and mass spectrometry provide evidence that the mutant is making a CSAD protein identical to that of the wild-type (XP_009295318.1) in terms of size, activity, and amino acid sequence. UAG readthrough has been described in several species, but this is the first presentation of a case in fish. Also presented are the first data substantiating the ability of a fish CSAD to utilize cysteic acid, an alternative to the standard substrate cysteine sulfinic acid, to produce taurine.
Asunto(s)
Codón de Terminación/genética , Biosíntesis de Proteínas/genética , Taurina/genética , Pez Cebra/genética , Secuencia de Aminoácidos , Aminoácidos/genética , Animales , Carboxiliasas/genética , Ácido Cisteico/metabolismo , Mutación Puntual/genéticaRESUMEN
Hyper-beta-alaninemia is a rare metabolic condition that results in elevated plasma and urinary ß-alanine levels and is characterized by neurotoxicity, hypotonia, and respiratory distress. It has been proposed that at least some of the symptoms are caused by oxidative stress; however, only limited information is available on the mechanism of reactive oxygen species generation. The present study examines the hypothesis that ß-alanine reduces cellular levels of taurine, which are required for normal respiratory chain function; cellular taurine depletion is known to reduce respiratory function and elevate mitochondrial superoxide generation. To test the taurine hypothesis, isolated neonatal rat cardiomyocytes and mouse embryonic fibroblasts were incubated with medium lacking or containing ß-alanine. ß-alanine treatment led to mitochondrial superoxide accumulation in conjunction with a decrease in oxygen consumption. The defect in ß-alanine-mediated respiratory function was detected in permeabilized cells exposed to glutamate/malate but not in cells utilizing succinate, suggesting that ß-alanine leads to impaired complex I activity. Taurine treatment limited mitochondrial superoxide generation, supporting a role for taurine in maintaining complex I activity. Also affected by taurine is mitochondrial morphology, as ß-alanine-treated fibroblasts undergo fragmentation, a sign of unhealthy mitochondria that is reversed by taurine treatment. If left unaltered, ß-alanine-treated fibroblasts also undergo mitochondrial apoptosis, as evidenced by activation of caspases 3 and 9 and the initiation of the mitochondrial permeability transition. Together, these data show that ß-alanine mediates changes that reduce ATP generation and enhance oxidative stress, factors that contribute to heart failure.
Asunto(s)
Trastornos de Somnolencia Excesiva/metabolismo , Mitocondrias Cardíacas/metabolismo , Enfermedades Mitocondriales/metabolismo , Miocitos Cardíacos/metabolismo , Convulsiones/metabolismo , beta-Alanina/metabolismo , beta-Alanina/toxicidad , Animales , Trastornos de Somnolencia Excesiva/genética , Trastornos de Somnolencia Excesiva/patología , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Ratones , Mitocondrias Cardíacas/genética , Mitocondrias Cardíacas/patología , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/patología , Miocitos Cardíacos/patología , Consumo de Oxígeno , Ratas , Convulsiones/genética , Convulsiones/patología , Taurina/biosíntesis , Taurina/genética , beta-Alanina/genéticaRESUMEN
BACKGROUND Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. In vitro, cultured colon cancer cell lines HCT-116 and LoVo were used as cell models. TUG1 and p63 were silenced via transferring siRNA into HCT-116 or LoVo. The effects of TUG1 were investigated by examining cell proliferation, apoptosis, and migration. RESULTS Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues compared with the matched adjacent non-tumor tissue, while p63 expression was lower in the tumor tissue. In HCT-116 and LoVo, the expression of TUG1 was significantly increased by p63 siRNA transfection. Furthermore, down-regulation of TUG1 by siRNA significantly inhibited the cell proliferation and promoted colon cancer cell apoptosis. In addition, inhibition of TUG1 expression significantly blocked the cell migration ability of colon cancer cells. CONCLUSIONS LncRNA TUG1 may serve as a potential oncogene for colon cancer. Overexpressed TUG1 may contribute to promoting cell proliferation and migration in colon cancer cells.
Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , ARN Largo no Codificante/biosíntesis , ARN Largo no Codificante/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/fisiología , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Neoplasias del Colon/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Taurina/genética , Taurina/metabolismo , Regulación hacia ArribaRESUMEN
The role of NOD-like receptor family (NLRP3) has been confirmed in various inflammatory diseases. The association between NLRP3 and hyper-bileacidaemia during the sepsis remains unclear. We aimed to investigate whether NLRP3 silencing protects against the sepsis-induced hyper-bileacidaemia. Sepsis was induced by caecum ligation and puncture (CLP). Gene silencing of NLRP3 was performed by injecting rats with NLRP3 short hairpin RNA plasmids (NLRP3 shRNA) 48 h before surgery. Rats were divided into four groups: group 1: sham; group 2: sepsis; group 3: NLRP3 shRNA + sepsis (called the 'NLRP3 shRNA' group); and group 4: scrambled shRNA + sepsis (called the 'scrambled shRNA' group). The serum levels of bile acids, hepatic expression of hepatocyte membrane transporters, hepatic cytokine levels and behaviours of immune cells were compared among the groups. Hepatic NLRP3 expression was increased dramatically during the sepsis, but was suppressed by pretreatment with NLRP3 shRNA. Compared with rats in the sepsis and the scrambled shRNA groups, rats in the NLRP3 shRNA group exhibited significantly decreased serum levels of glycine and taurine conjugated-bile acids, with rehabilitated expression of hepatocyte transporters, suppressed hepatic cytokine levels, decreased hepatic neutrophils infiltration and attenuated macrophages pyroptosis. Gene silencing of NLRP3 ameliorates sepsis-induced hyper-bileacidaemia by rehabilitating hepatocyte transporter expression, reducing hepatic cytokine levels, neutrophil infiltration and macrophages pyroptosis. NLRP3 may be a pivotal target for sepsis management.
Asunto(s)
Silenciador del Gen , Hiperbilirrubinemia/sangre , Hígado/metabolismo , Neutrófilos/metabolismo , Receptores Citoplasmáticos y Nucleares , Sepsis/sangre , Animales , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/genética , Proteínas Portadoras , Citocinas/genética , Citocinas/metabolismo , Glicina/sangre , Glicina/genética , Hepatocitos/metabolismo , Hepatocitos/patología , Hiperbilirrubinemia/genética , Hiperbilirrubinemia/patología , Hiperbilirrubinemia/terapia , Hígado/patología , Macrófagos/metabolismo , Macrófagos/patología , Proteína con Dominio Pirina 3 de la Familia NLR , Infiltración Neutrófila/genética , Neutrófilos/patología , Ratas , Ratas Sprague-Dawley , Sepsis/genética , Sepsis/patología , Sepsis/terapia , Taurina/sangre , Taurina/genéticaRESUMEN
It has been suggested that invertebrates inhabiting deep-sea hydrothermal vent areas use the sulfinic acid hypotaurine, a precursor of taurine, to protect against the toxicity of hydrogen sulfide contained in the seawater from the vent. In this protective system, hypotaurine is accumulated in the gill, the primary site of sulfide exposure. However, the pathway for hypotaurine synthesis in mollusks has not been identified. In this study, we screened for the mRNAs of enzymes involved in hypotaurine synthesis in the deep-sea mussel Bathymodiolus septemdierum and cloned cDNAs encoding cysteine dioxygenase and cysteine sulfinate decarboxylase. As mRNAs encoding cysteamine dioxygenase and cysteine lyase were not detected, the cysteine sulfinate pathway is suggested to be the major pathway of hypotaurine and taurine synthesis. The two genes were found to be expressed in all the tissues examined, but the gill exhibited the highest expression. The mRNA level in the gill was not significantly changed by exposure to sulfides or thiosulfate. These results suggests that the gill of B. septemdierum maintains high levels of expression of the two genes regardless of ambient sulfide level and accumulates hypotaurine continuously to protect against sudden exposure to high level of sulfide.
Asunto(s)
Adaptación Fisiológica , Bivalvos , Carboxiliasas , Cisteína-Dioxigenasa , Sulfuro de Hidrógeno/metabolismo , Taurina/análogos & derivados , Animales , Bivalvos/enzimología , Bivalvos/genética , Carboxiliasas/biosíntesis , Carboxiliasas/genética , Cisteína-Dioxigenasa/biosíntesis , Cisteína-Dioxigenasa/genética , Taurina/biosíntesis , Taurina/genéticaRESUMEN
Our investigation showed that hepatocytes isolated from cysteine dioxygenase knockout mice (Cdo1(-/-)) had lower levels of hypotaurine and taurine than Cdo1 (+/+) hepatocytes. Interestingly, hypotaurine accumulates in cultured wild-type hepatocytes. DL-propargylglycine (PPG, inhibitor of cystathionine γ-lyase and H2S production) dramatically decreased both taurine and hypotaurine levels in wild-type hepatocytes compared to untreated cells. Addition of 2 mM PPG resulted in the decrease of the intracellular taurine levels: from 10.25 ± 5.00 observed in control, to 2.53 ± 0.68 nmol/mg protein (24 h of culture) and from 17.06 ± 9.40 to 2.43 ± 0.26 nmol/mg protein (control vs. PPG; 48 h). Addition of PPG reduced also intracellular hypotaurine levels: from 7.46 ± 3.55 to 0.31 ± 0.12 nmol/mg protein (control vs. PPG; 24 h) and from 4.54 ± 3.20 to 0.42 ± 0.11 nmol/mg protein (control vs. PPG; 48 h). The similar effects of PPG on hypotaurine and taurine levels were observed in culture medium. PPG blocked hypotaurine/taurine synthesis in wild-type hepatocytes, suggesting that it strongly inhibits cysteinesulfinate decarboxylase (pyridoxal 5'-phosphate-dependent enzyme) as well as cystathionine γ-lyase. In the presence of PPG, intracellular and medium cystathionine levels for both wild-type and Cdo1 (-/-) cells were increased. Addition of homocysteine or methionine resulted in higher intracellular concentrations of homocysteine, which is a cosubstrate for cystathionine ß-synthase (CBS). It seems that PPG increases CBS-mediated desulfhydration by enhancing homocysteine levels in hepatocytes. There were no overall effects of PPG or genotype on intracellular or medium glutathione levels.
Asunto(s)
Alquinos/farmacología , Cistationina/metabolismo , Glicina/análogos & derivados , Hepatocitos/metabolismo , Homocisteína/metabolismo , Taurina/análogos & derivados , Animales , Células Cultivadas , Cistationina/genética , Cisteína-Dioxigenasa/genética , Cisteína-Dioxigenasa/metabolismo , Femenino , Glicina/farmacología , Hepatocitos/citología , Homocisteína/genética , Masculino , Ratones , Ratones Noqueados , Cultivo Primario de Células , Taurina/biosíntesis , Taurina/genéticaRESUMEN
Taurine is an abundant ß-amino acid that concentrates in the mitochondria, where it participates in the conjugation of tRNAs for leucine, lysine, glutamate and glutamine. The formation of 5-taurinomethyluridine-tRNA strengthens the interaction of the anticodon with the codon, thereby promoting the decoding of several codons, including those for AAG, UUG, CAG and GAG. By preventing these series of events, taurine deficiency appears to diminish the formation of 5-taurinomethyluridine and causes inefficient decoding for the mitochondrial codons of leucine, lysine, glutamate and glutamine. The resulting reduction in the biosynthesis of mitochondria-encoded proteins deprives the respiratory chain of subunits required for the assembly of respiratory chain complexes. Hence, taurine deficiency is associated with a reduction in oxygen consumption, an elevation in glycolysis and lactate production and a decline in ATP production. A similar sequence of events takes place in mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fiber syndrome). In both diseases, mutations in their respective tRNAs interfere with the formation of 5-taurinomethyluridine in the wobble position. Hence, the taurine-deficient phenotype resembles the phenotypes of MELAS and MERRF.
Asunto(s)
Síndrome MERRF/mortalidad , Mitocondrias/metabolismo , Miopatías Mitocondriales/metabolismo , Proteínas Mitocondriales/metabolismo , Taurina/metabolismo , Animales , Codón de Terminación/genética , Codón de Terminación/metabolismo , Transporte de Electrón/genética , Glucólisis/genética , Humanos , Síndrome MERRF/genética , Síndrome MERRF/patología , Mitocondrias/genética , Mitocondrias/patología , Miopatías Mitocondriales/genética , Miopatías Mitocondriales/patología , Proteínas Mitocondriales/genética , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Taurina/genética , Uridina/análogos & derivados , Uridina/genética , Uridina/metabolismoRESUMEN
The GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [(3)H]taurine. Furthermore, most of the uptake of [(3)H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain.
Asunto(s)
Encéfalo/metabolismo , Proteínas Transportadoras de GABA en la Membrana Plasmática/metabolismo , Hígado/metabolismo , Taurina/metabolismo , Animales , Encéfalo/citología , Química Encefálica , Proteínas Transportadoras de GABA en la Membrana Plasmática/genética , Células HEK293 , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Corteza Renal/citología , Corteza Renal/metabolismo , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/metabolismo , Hígado/citología , Masculino , Ratones , Ratones Noqueados , Conejos , Ratas , Ratas Wistar , Taurina/genéticaRESUMEN
Variations in the genetic code are found frequently in mitochondrial decoding systems. Four non-universal genetic codes are employed in ascidian mitochondria: AUA for Met, UGA for Trp, and AGA/AGG(AGR) for Gly. To clarify the decoding mechanism for the non-universal genetic codes, we isolated and analyzed mitochondrial tRNAs for Trp, Met, and Gly from an ascidian, Halocynthia roretzi. Mass spectrometric analysis identified 5-taurinomethyluridine (τm(5)U) at the anticodon wobble positions of tRNA(Met)(AUR), tRNA(Trp)(UGR), and tRNA(Gly)(AGR), suggesting that τm(5)U plays a critical role in the accurate deciphering of all four non-universal codes by preventing the misreading of pyrimidine-ending near-cognate codons (NNY) in their respective family boxes. Acquisition of the wobble modification appears to be a prerequisite for the genetic code alteration.
Asunto(s)
Anticodón/metabolismo , Mitocondrias/metabolismo , ARN/metabolismo , Taurina/metabolismo , Uridina/metabolismo , Urocordados/metabolismo , Animales , Anticodón/genética , Mitocondrias/genética , ARN/genética , ARN Mitocondrial , Taurina/genética , Uridina/genética , Urocordados/genéticaRESUMEN
The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is reduced following reduction in osmolarity, keeping the extracellular Na(+) concentration constant. TonEBP activity is unaltered, whereas TauT transcription as well as TauT activity are significantly reduced under hypo-osmotic conditions. In contrast, TonEBP activity and TauT transcription are significantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H(2)O(2) or overexpressing NOX4, we demonstrate that TonEBP activity and taurine influx are regulated negatively by ROS under hypo-osmotic, low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure to ROS reduces taurine uptake as a result of modulated TauT transport kinetics. Thus, swelling-induced ROS production could account for the reduced taurine uptake under low-sodium/hypo-osmotic conditions by direct modulation of TauT.
Asunto(s)
Fibroblastos/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Estrés Fisiológico/fisiología , Animales , Células Cultivadas , Regulación hacia Abajo , Peróxido de Hidrógeno/metabolismo , Soluciones Hipertónicas , Soluciones Hipotónicas , Cinética , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/genética , Ratones , NADPH Oxidasa 4 , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Células 3T3 NIH , Ósmosis , ARN Mensajero/genética , Especies Reactivas de Oxígeno/metabolismo , Sodio/metabolismo , Taurina/genética , Taurina/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Equilibrio HidroelectrolíticoRESUMEN
In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate.
Asunto(s)
Disuasivos de Alcohol/uso terapéutico , Alcoholismo/tratamiento farmacológico , Alcoholes/metabolismo , Factor Natriurético Atrial/genética , Factor de Transcripción GATA4/genética , Taurina/análogos & derivados , Acamprosato , Adulto , Alcoholismo/genética , Alcoholismo/patología , Factor Natriurético Atrial/sangre , Femenino , Factor de Transcripción GATA4/metabolismo , Dosificación de Gen , Estudios de Asociación Genética , Variación Genética , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Riesgo , Taurina/genética , Taurina/uso terapéuticoRESUMEN
Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-ß1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling.
Asunto(s)
Antioxidantes/farmacología , Cirrosis Hepática/tratamiento farmacológico , Antígeno 96 de los Linfocitos/genética , Taurina/farmacología , Receptor Toll-Like 4/genética , Actinas/genética , Animales , Caspasa 3/genética , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Simulación del Acoplamiento Molecular , FN-kappa B/genética , Unión Proteica/efectos de los fármacos , Ratas , Albúmina Sérica/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Taurina/genética , Tioacetamida/toxicidadRESUMEN
The fungus Curvularia protuberata carries a dsRNA virus, Curvularia thermal tolerance virus, and develops a three-way symbiotic relationship with plants to enable their survival in extreme soil temperatures. To learn about the genome of C. protuberata and possible mechanisms of heat tolerance a collection of expressed sequence tags (ESTs) were developed from two subtracted cDNA libraries from mycelial cultures grown under control and heat stress conditions. We analyzed 4207 ESTs that were assembled into 1926 unique transcripts. Of the unique transcripts, 1347 (70%) had sequence similarity with GenBank entries using BLASTX while the rest represented unknown proteins with no matches in the databases. The majority of ESTs with known similarities were homologues to fungal genes. The EST collection presents a rich source of heat stress and viral induced genes of a fungal endophyte that is involved in a symbiotic relationship with plants. Expression profile analyses of some candidate genes suggest possible involvement of osmoprotectants such as trehalose, glycine betaine, and taurine in the heat stress response. The fungal pigment melanin, and heat shock proteins also may be involved in the thermotolerance of C. protuberata in culture. The results assist in understanding the molecular basis of thermotolerance of the three-way symbiosis. Further studies will confirm or refute the involvement of these pathways in stress tolerance.
Asunto(s)
Ascomicetos/fisiología , Ascomicetos/virología , Respuesta al Choque Térmico/genética , Poaceae/microbiología , Simbiosis/genética , Ascomicetos/genética , Betaína/metabolismo , Catalasa/genética , ADN Complementario/genética , ADN de Hongos/genética , Etiquetas de Secuencia Expresada , Perfilación de la Expresión Génica , Glutatión Transferasa/genética , Proteínas de Choque Térmico/genética , Melaninas/genética , Taurina/genética , Trehalosa/genéticaRESUMEN
BACKGROUND: Neonatal pneumonia (NP) has a high fatality rate in neonatal illness. This research investigated the functions of emodin on lipopolysaccharide (LPS)-evoked inflammatory injury in WI-38 cells. METHODS: Cell counting kit-8 (CCK-8) assay and flow cytometry were utilized for examining the impacts of LPS and emodin on viability and apoptosis, respectively. Taurine up-regulated gene 1 (TUG1) level was altered through cell transfection and investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, RT-qPCR, western blot and enzyme-linked immunosorbent assay (ELISA) were utilized for investigating expressions of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. Western blot was carried out for investigating the levels of Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3 and NF-κB and p38MAPK pathway-related proteins. RESULTS: LPS treatment restrained cell viability, enhanced apoptosis, and expressions of inflammation-related IL-6 and MCP-1. Emodin alleviated LPS-evoked inflammatory injury and restrained the NF-κB and p38MAPK pathways. Furthermore, emodin positively regulated TUG1 expression and TUG1 silencing could reverse the efficacy of emodin on IL-6 and MCP-1 expressions. Finally, TUG1 regulates the expression of inflammatory factors through NF-κB and p38MAPK pathways. CONCLUSION: Emodin alleviated LPS-evoked inflammatory injury by raising TUG1 expression via NF-κB and p38MAPK pathways in WI-38 cells.
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Emodina/farmacología , Inflamación/tratamiento farmacológico , ARN Largo no Codificante/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Quimiocina CCL2/genética , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Interleucina-6/genética , Lipopolisacáridos/toxicidad , FN-kappa B/genética , ARN Largo no Codificante/antagonistas & inhibidores , Taurina/genética , Activación Transcripcional/efectos de los fármacosRESUMEN
Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, but therapeutic treatment options are limited. Taurine has been reported to have neuroprotective properties against dementia, including AD. The present study aimed to investigate the treatment effect of taurine in AD mice by functional molecular imaging. To elucidate glutamate alterations by taurine, taurine was administered to 5xFAD transgenic mice from 2 months of age, known to apear amyloid deposition. Then, we performed glutamate positron emission tomography (PET) imaging studies for three groups (wild-type, AD, and taurine-treated AD, n = 5 in each group). As a result, brain uptake in the taurine-treated AD group was 31-40% higher than that in the AD group (cortex: 40%, p < 0.05; striatum: 32%, p < 0.01; hippocampus: 36%, p < 0.01; thalamus: 31%, p > 0.05) and 3-14% lower than that in the WT group (cortex: 10%, p > 0.05; striatum: 15%, p > 0.05; hippocampus: 14%, p > 0.05; thalamus: 3%, p > 0.05). However, we did not observe differences in Aß pathology between the taurine-treated AD and AD groups in immunohistochemistry experiments. Our results reveal that although taurine treatment did not completely recover the glutamate system, it significantly increased metabolic glutamate receptor type 5 brain uptake. Therefore, taurine has therapeutic potential against AD.
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Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/genética , Fármacos Neuroprotectores/farmacología , Taurina/farmacología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Modelos Animales de Enfermedad , Hipocampo/diagnóstico por imagen , Hipocampo/efectos de los fármacos , Humanos , Imagen por Resonancia Magnética , Ratones , Ratones Transgénicos , Tomografía de Emisión de Positrones , Taurina/genéticaRESUMEN
INTRODUCTION: Golden retrievers are over-represented in cases of taurine-deficient dilated cardiomyopathy and recently a surge in cases has prompted further investigation. OBJECTIVE: To describe the clinical, dietary, and echocardiographic features in golden retrievers diagnosed with taurine deficiency and dilated cardiomyopathy, and to determine specific dietary associations. A second aim was to determine the whole blood taurine concentrations in a representative sample of healthy golden retrievers. ANIMALS: Twenty-four client-owned golden retrievers with documented taurine deficiency and dilated cardiomyopathy and 52 healthy client-owned golden retrievers. METHODS: In this multicenter prospective observational study, baseline and follow-up echocardiographic data, complete diet and medical histories, and whole blood, plasma, or serum taurine concentrations were obtained. Baseline and follow-up echocardiographic data were compared. Associations were evaluated between specific diets and taurine deficiency or congestive heart failure. The prevalence of low whole blood taurine concentrations in the healthy golden retrievers was calculated. RESULTS: Twenty-three of 24 dogs diagnosed with taurine deficiency and dilated cardiomyopathy were fed diets that were either grain-free, legume-rich, or a combination of these factors. None of these diets were feeding trial tested using Association of American Feed Control Officials (AAFCO) procedures. Twenty-three of 24 dogs had significant improvement in their echocardiographic parameters and normalization of taurine concentrations following diet change and taurine supplementation. Nine of 11 dogs diagnosed with congestive heart failure (CHF) had resolution of their congestion at follow-up with five no longer requiring diuretic therapy and four tolerating diuretic dose reduction by >50%. CONCLUSIONS: Certain diets and diet characteristics were associated with the development of taurine deficiency. Taurine deficiency and dilated cardiomyopathy in golden retrievers is likely multifactorial, including a combination of dietary, metabolic, and genetic factors.
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Cardiomiopatía Dilatada/diagnóstico , Dieta/efectos adversos , Enfermedades de los Perros/diagnóstico , Taurina/metabolismo , Alimentación Animal/efectos adversos , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/fisiopatología , Dieta/veterinaria , Enfermedades de los Perros/etiología , Enfermedades de los Perros/fisiopatología , Perros , Ecocardiografía , Grano Comestible/efectos adversos , Femenino , Corazón/diagnóstico por imagen , Corazón/fisiopatología , Masculino , Taurina/deficiencia , Taurina/genéticaRESUMEN
We previously reported that several markers on rat chromosome (Chr) 4 cosegregated with the occurrence of cerebral stroke and brain edema in stroke-prone spontaneously hypertensive rats (SHRSP). To obtain insights into the positional candidate genes for stroke susceptibility in this region, we mapped four genes, Taurine transporter (Tau), tumor necrosis factor receptor (Tnfr), GABA transporter (Gat1) and glucose transporter-3 (Glut3) genes, using newly developed simple sequence repeat (SSR) markers on rat Chr 4. We isolated the SSRs for the genes either by screening a rat genomic library or by searching the GenBank database. By linkage analysis using two sets of backcrosses, Gat1 and Tnfr were mapped in the region associated with stroke, while Taut was located distant from the region. The Glut3 locus was also assigned to rat Chr 4 using a rat x mouse hybrid clone panel. These results indicated that the Tnfr, Gat1 and Glut3 genes were good positional candidates for the stroke susceptibility in SHRSP, suggesting that further evaluation of these genes by functional studies could prove useful.