RESUMEN
Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.
Asunto(s)
Linfocitos T CD8-positivos , Glicoproteínas de Membrana , Taurina , Taurina/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Animales , Humanos , Ratones , Línea Celular Tumoral , Ratones Endogámicos C57BL , Estrés del Retículo Endoplásmico , Factor de Transcripción Activador 4/metabolismo , Transducción de Señal , Femenino , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
The broad contemporary applications of silver nanoparticles (AgNPs) have been associated with various toxicities including reproductive toxicity. Taurine is well acknowledged for its potent pharmacological role in numerous disease models and chemically-mediated toxicity. We investigated the effect of taurine on AgNPs-induced reproductive toxicity in male rats. The animals were intraperitoneally injected with AgNPs (200 µg/kg) alone or co-administered with taurine at 50 and 100 mg/kg for 21 successive days. Exogenous taurine administration significantly abated AgNPs-induced oxidative injury by decreasing the levels of oxidative stress indices while boosting antioxidant enzymes activities and glutathione level in the hypothalamus, testes and epididymis of exposed animals. Taurine administration alleviated AgNPs-induced inflammatory response and caspase-3 activity, an apoptotic biomarker. Moreover, taurine significantly improved spermiogram, reproductive hormones and the marker enzymes of testicular function in AgNPs-treated animals. The ameliorative effect of taurine on pathological lesions induced by AgNPs in the exposed animals was substantiated by histopathological data. This study provides the first mechanistic evidence that taurine supplementation affords therapeutic effect against reproductive dysfunction associated with AgNPs exposure in male rats.
Asunto(s)
Nanopartículas del Metal , Plata , Ratas , Masculino , Animales , Plata/toxicidad , Ratas Wistar , Nanopartículas del Metal/toxicidad , Taurina/farmacología , Taurina/metabolismo , Testículo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estrés OxidativoRESUMEN
It has been well established that the circulating taurine affects the insulin synthesis in pancreatic islet ß-cells, whereas miR-7a and LIM-homeodomain transcription factor Isl-1 are important intracellular factors regulating insulin transcription and synthesis. However, it still remains unknown whether taurine regulates insulin synthesis by affecting miR-7a and/or Isl-1 expressions in mouse pancreatic islet ß-cells. The present study was thus proposed to identify the effects of taurine on the expressions of miR-7a and/or Isl-1 and their relations to insulin synthesis in mouse pancreatic islet ß-cells by using miR-7a2 knockout (KO) and taurine transporter (TauT) KO mouse models and the related in vitro experiments. The results demonstrated that taurine supplement significantly decreased the pancreas miR-7a expression, but sharply upregulated the pancreas Isl-1 and insulin expressions, and serum insulin levels. However, the enhanced effects of taurine on Isl-1 expression and insulin synthesis were mitigated in the TauT KO and miR-7a2 KO mice. In addition, our results confirmed that taurine markedly increased pancreas RAF1 and ERK1/2 expressions. Collectively, the present study firstly demonstrates that taurine regulates insulin synthesis through TauT/miR-7a/RAF1/ERK1/2/Isl-1 signaling pathway, which are crucial for our understanding the mechanisms of taurine affecting insulin synthesis, and also potential for establishing the therapeutic strategies for diabetes and the diseases related to metabolism.
Asunto(s)
Células Secretoras de Insulina , MicroARNs , Animales , Ratones , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones Noqueados , MicroARNs/genética , MicroARNs/metabolismo , Taurina/farmacología , Taurina/metabolismoRESUMEN
Taurine, a naturally occurring sulfur-containing amino acid, has attracted significant attention in recent years due to its potential health benefits. Found in various foods and often used in energy drinks and supplements, taurine has been studied extensively to understand its impact on human physiology. Determining its exact functional roles represents a complex and multifaceted topic. We provide an overview of the scientific literature and present an analysis of the effects of taurine on various aspects of human health, focusing on aging and cardiovascular pathophysiology, but also including athletic performance, metabolic regulation, and neurological function. Additionally, our report summarizes the current recommendations for taurine intake and addresses potential safety concerns. Evidence from both human and animal studies indicates that taurine may have beneficial cardiovascular effects, including blood pressure regulation, improved cardiac fitness, and enhanced vascular health. Its mechanisms of action and antioxidant properties make it also an intriguing candidate for potential anti-aging strategies.
Asunto(s)
Corazón , Taurina , Animales , Humanos , Taurina/farmacología , Taurina/metabolismo , Antioxidantes/farmacología , Suplementos Dietéticos , EnvejecimientoRESUMEN
This study investigated the effects of dietary supplementation with taurine (TAU) on the meat quality, muscle fiber type, and mitochondrial function of finishing pigs. The results demonstrated that TAU significantly increased the a* value while decreasing b*45 min, L*24 h, and drip loss24 h and drip loss48 h in the longissimus dorsi (LD) muscle. Dietary supplemented with TAU reduced the content of lactate and the glycolytic potential (GP) in the LD muscle. Dietary supplemented with TAU enhanced the oxidative fiber-related gene expression as well as increased succinic dehydrogenase and malate dehydrogenase activities while reducing lactate dehydrogenase activity. Furthermore, dietary supplementation with TAU increased the contents of mtDNA and ATP and mitochondrial function-related gene expression. Moreover, TAU enhanced the mRNA expressions of calcineurin (CaN) and nuclear factor of activated T cells c1 (NFATc1) and protein expressions of CNA and NFATc1. The results indicate that dietary TAU supplementation improves meat quality and mitochondrial biogenesis and function and promotes muscle fiber-type conversion from the glycolytic fiber to the oxidative fiber via the CaN/NFATc1 pathway.
Asunto(s)
Fibras Musculares Esqueléticas , Taurina , Porcinos/genética , Taurina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Suplementos Dietéticos , Carne/análisis , Mitocondrias , Alimentación Animal/análisis , AnimalesRESUMEN
BACKGROUND: Researches on diagnosis and treatment of Alzheimer's disease, the most common type of dementia, are still ongoing. Taurine is frequently used in Alzheimer's disease models due to its protective effects. Metal cation dyshomeostasis is an important etiological factor for Alzheimer's disease. Transthyretin protein is thought to act as a transporter for the Aß protein that accumulates in the brain and is eliminated in the liver and kidneys via the LRP-1 receptor. However, the effect of taurine on this mechanisms is not fully known. METHODS: 30 male rats, aged 28 ± 4 months, were divided into 5 groups (n = 6) as follows: control group, sham group, Aß 1-42 group, taurine group and taurine+Aß 1-42 group. Oral taurine pre-supplementation was given as 1000 mg/kg-body weight/day for 6 weeks to taurine and taurine+Aß 1-42 groups. RESULTS: Plasma copper, heart transthyretin and Aß 1-42, brain and kidney LRP-1 levels were found to be decreased in the Aß 1-42 group. Brain transthyretin was higher in taurine+Aß 1-42 group and brain Aß 1-42 was higher in Aß 1-42 and taurine+Aß 1-42 groups. CONCLUSION: Taurine pre-supplementation maintained cardiac transthyretin levels, decreased cardiac Aß 1-42 levels and increased brain and kidney LRP-1 levels. Taurine may have a potential to be used as a protective agent for aged people at high risk for Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer , Ratas , Masculino , Animales , Enfermedad de Alzheimer/etiología , Prealbúmina/metabolismo , Prealbúmina/farmacología , Taurina/farmacología , Taurina/metabolismo , Encéfalo/metabolismo , Hígado/metabolismo , Metales/metabolismo , Péptidos beta-Amiloides/metabolismoRESUMEN
This research aimed to investigate the synergistic protective effect of exercise training and taurine on Akt-Foxo3a-Caspase-8 signaling related to infarct size and cardiac dysfunction. Therefore, 25 male Wistar rats with MI were divided into five groups: sham (Sh), control-MI(C-MI), exercise training-MI(Exe-MI), taurine supplementation-MI(Supp-MI), and exercise training + taurine-MI(Exe + Supp-MI). The taurine groups were given a 200 mg/kg/day dose of taurine by drinking water. Exercise training was conducted for 8 weeks (5 days/week), each session alternated 2 min with 25-30% VO2peak and 4 min with 55-60% VO2peak for 10 alternations. Then, the left ventricle tissue samples were taken from all groups. Exercise training and taurine activated Akt and decreased Foxo3a. Expression of the caspase-8 gene was increased in cardiac necrosis after MI, While, after 12 weeks of intervention decreased. Results exhibited that exercise training combined with taurine has a greater effect than either alone on activating the Akt-Foxo3a-caspase signaling pathway (P < 0.001). MI-induced myocardial injury leads to increase collagen deposition (P < 0.001) and infarct size and results in cardiac dysfunction via reduced stroke volume, ejection fraction, and fractional shortening (P < 0.001). Exercise training and taurine improved cardiac functional parameters (SV, EF, FS) and infarct size (P < 0.001) after 8 weeks of intervention in rats with MI. Also, the interaction of exercise training and taurine has a greater effect than alone on these variables. Interaction of exercise training with taurine supplementation induces a general amelioration of the cardiac histopathological profiles and improves cardiac remodeling via activating Akt-Foxo3a-Caspase-8 signaling with protective effects against MI.
Asunto(s)
Infarto del Miocardio , Condicionamiento Físico Animal , Animales , Masculino , Ratas , Caspasa 8/genética , Caspasa 8/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Miocardio/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Wistar , Transducción de Señal , Taurina/metabolismo , Taurina/farmacología , Taurina/uso terapéuticoRESUMEN
Phenylpropionamides in the seed of Cannabis sativa L. (PHS) have a protective effect on neuroinflammation and antioxidant activity. In this study, the UHPLC-Orbitrap-fusion-TMS-based metabolomics approach was used to analyze the serum samples and identify potential biomarkers in Streptozotocin (STZ) induced Alzheimer's disease (AD) rats. The results revealed that primary bile acid biosynthesis and taurine and hypotaurine metabolism were significantly correlated with STZ-induced AD rats. In addition, the key enzymes in these two pathways were verified at the protein level. The levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD), cysteamine (2-aminoethanethiol) dioxygenase (ADO), 7α-hydroxylase (CYP7A1), and sterol 12α-hydroxylase (CYP8B1) were the key enzymes affecting the two pathways in AD rats compared with the control group (CON). Furthermore, after a high-dose group of phenylpropionamides in the seed of Cannabis sativa L. (PHS-H) was administrated, the levels of CDO1, CSAD, CYP7A1, and CYP8B1 were all callback. These findings demonstrate for the first time that the anti-AD effect of PHS is associated with the regulation of primary bile acid biosynthesis and taurine and hypotaurine metabolism in STZ-induced AD rats.
Asunto(s)
Enfermedad de Alzheimer , Cannabis , Ratas , Animales , Esteroide 12-alfa-Hidroxilasa , Cromatografía Líquida de Alta Presión , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Taurina/metabolismo , Taurina/farmacología , Ácidos y Sales Biliares , MetabolómicaRESUMEN
Sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53-/- cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.
Asunto(s)
Aminoácidos Sulfúricos , Carcinoma de Células Renales , Neoplasias del Colon , Neoplasias Renales , Neoplasias Ováricas , Ratones , Animales , Femenino , Humanos , Aminoácidos Sulfúricos/metabolismo , Caseínas , Leucina , Ratones Endogámicos C57BL , Metionina/metabolismo , Cisteína/metabolismo , Dieta , Taurina/metabolismo , Racemetionina , LípidosRESUMEN
Deoxynivalenol (DON), as a widespread Fusarium mycotoxin in cereals, food products, and animal feed, is detrimental to both human and animal health. The liver is not only the primary organ responsible for DON metabolism but also the principal organ affected by DON toxicity. Taurine is well known to display various physiological and pharmacological functions due to its antioxidant and anti-inflammatory properties. However, the information regarding taurine supplementation counteracting DON-induced liver injury in piglets is still unclear. In our work, twenty-four weaned piglets were subjected to four groups for a 24-day period, including the BD group (a basal diet), the DON group (3 mg/kg DON-contaminated diet), the DON+LT group (3 mg/kg DON-contaminated diet + 0.3% taurine), and the DON+HT group (3 mg/kg DON-contaminated diet + 0.6% taurine). Our findings indicated that taurine supplementation improved growth performance and alleviated DON-induced liver injury, as evidenced by the reduced pathological and serum biochemical changes (ALT, AST, ALP, and LDH), especially in the group with the 0.3% taurine. Taurine could counteract hepatic oxidative stress in piglets exposed to DON, as it reduced ROS, 8-OHdG, and MDA concentrations and improved the activity of antioxidant enzymes. Concurrently, taurine was observed to upregulate the expression of key factors involved in mitochondrial function and the Nrf2 signaling pathway. Furthermore, taurine treatment effectively attenuated DON-induced hepatocyte apoptosis, as verified through the decreased proportion of TUNEL-positive cells and regulation of the mitochondria-mediated apoptosis pathway. Finally, the administration of taurine was able to reduce liver inflammation due to DON, by inactivating the NF-κB signaling pathway and declining the production of pro-inflammatory cytokines. In summary, our results implied that taurine effectively improved DON-induced liver injury. The underlying mechanism should be that taurine restored mitochondrial normal function and antagonized oxidative stress, thereby reducing apoptosis and inflammatory responses in the liver of weaned piglets.
Asunto(s)
Antioxidantes , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Animales , Humanos , Porcinos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Taurina/farmacología , Taurina/uso terapéutico , Taurina/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Hígado , Estrés Oxidativo , Inflamación/metabolismo , Suplementos Dietéticos , Apoptosis , Mitocondrias/metabolismo , Alimentación Animal/análisisRESUMEN
N-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans. However, the synthesis pathway of the PUFA-containing NATs remains undiscovered. Here, we report that human livers synthesize NATs and that the acyl-chain preference is similar in murine liver homogenates. In the mouse, we found that hepatic NAT synthase activity localizes to the peroxisome and depends upon an active-site cysteine. Using unbiased metabolomics and proteomics, we identified bile acid-CoA:amino acid N-acyltransferase (BAAT) as the likely hepatic NAT synthase in vitro. Subsequently, we confirmed that BAAT knockout livers lack up to 90% of NAT synthase activity and that biliary PUFA-containing NATs are significantly reduced compared with wildtype. In conclusion, we identified the in vivo PUFA-NAT synthase in the murine liver and expanded the known substrates of the bile acid-conjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.
Asunto(s)
Ácidos y Sales Biliares , Ácidos Grasos Omega-3 , Ratones , Humanos , Animales , Ácidos y Sales Biliares/metabolismo , Taurina/metabolismo , Hígado/metabolismo , Ácidos Grasos Insaturados/metabolismo , Aciltransferasas/metabolismo , Aminoácidos/metabolismo , Ácidos Grasos/metabolismo , Ácidos Grasos Omega-3/metabolismoRESUMEN
BACKGROUND: Pulses are an attractive alternative protein source for all mammals; however, recent reports suggest that these ingredients may be related to developing dilated cardiomyopathy in dogs. OBJECTIVES: The primary objective of this study was to quantify the effects of dietary pulse intake by adult dogs on cardiac function using echocardiographic measurements and cardiac biomarkers N-terminal pro-B-type natriuretic peptide and cardiac troponin I (cTnI). Second, to investigate the effects of pulse consumption on plasma sulfur amino acid (SAA) concentrations as pulses are generally low in SAA and may limit taurine synthesis. Last, to assess the general safety and efficacy of feeding pulse-containing diets on canine body composition and hematological and biochemical indices. METHODS: Twenty-eight privately-owned domestic Siberian Huskies (13 females; 4 intact, and 15 males; 6 intact) with a mean age of 5.3 ± 2.8 y (± SD) were randomly assigned to 1 of 4 dietary treatments (n = 7/treatment), with equal micronutrient supplementation and increasing whole pulse ingredient inclusion (0%, 15%, 30%, and 45%) with pea starch used to balance protein and energy. RESULTS: After 20 wks of feeding, there were no differences (P > 0.05) in echocardiographic parameters, N-terminal pro-B-type natriuretic peptide, and cTnI concentrations among treatments or across time within treatment (P > 0.05), indicating no differences in cardiac function among treatments. Concentrations of cTnI remained below the safe upper limit of 0.2 ng/mL for all dogs. Plasma SAA status, body composition, and hematological and biochemical indices were similar among treatments and over time (P > 0.05). CONCLUSIONS: The results from this study suggest that increasing the inclusion of pulses up to 45% with the removal of grains and equal micronutrient supplementation does not impact cardiac function concurrent with dilated cardiomyopathy, body composition, or SAA status and is safe for healthy adult dogs to consume when fed for 20 wks.
Asunto(s)
Aminoácidos Sulfúricos , Cardiomiopatía Dilatada , Animales , Perros , Femenino , Masculino , Alimentación Animal/análisis , Cardiomiopatía Dilatada/veterinaria , Pollos/metabolismo , Dieta/veterinaria , Mamíferos/metabolismo , Micronutrientes , Péptido Natriurético Encefálico , Pisum sativum , Almidón , Taurina/metabolismoRESUMEN
Taurine, a sulfur-containing amino acid, has a wide range of biological effects, such as bile salt formation, osmotic regulation, oxidative stress inhibition, immunomodulation and neuromodulation. Taurine has been proved to be synthesized and abundant in male reproductive organs. Recently, accumulating data showed that taurine has a potential protective effect on reproductive function of male animals. In physiology, taurine can promote the endocrine function of the hypothalamus-pituitary-testis (HPT) axis, testicular tissue development, spermatogenesis and maturation, delay the aging of testicular structure and function, maintain the homeostasis of the testicular environment, and enhance sexual ability. In pathology, taurine supplement may be beneficial to alleviate pathological damage of male reproductive system, including oxidative damage of sperm preservation in vitro, testicular reperfusion injury and diabetes -induced reproductive complications. In addition, taurine acts as a protective agent against toxic damage to the male reproductive system by exogenous substances (e.g., therapeutic drugs, environmental pollutants, radiation). Related mechanisms include reduced oxidative stress, increased antioxidant capacity, inhibited inflammation and apoptosis, restored the secretory activity of the HPT axis, reduced chromosomal variation, enhanced sperm mitochondrial energy metabolism, cell membrane stabilization effect, etc. Therefore, this article reviewed the protective effect of taurine on male reproductive function and its detailed mechanism, in order to provide reference for further research and clinical application.
Asunto(s)
Semen , Taurina , Ratas , Animales , Masculino , Taurina/farmacología , Taurina/metabolismo , Taurina/uso terapéutico , Ratas Wistar , Testículo/metabolismo , Antioxidantes/metabolismoRESUMEN
Oat supplementation of the ruminant diet can improve growth performance and meat quality traits, but the role of muscle metabolites has not been evaluated. This study aimed to establish whether oat grass supplementation (OS) of Small-tail Han sheep improved growth performance and muscle tissue metabolites that are associated with better meat quality and flavor. After 90-day, OS fed sheep had higher live-weight and carcass-weight, and lower carcass fat. Muscle metabolomics analysis showed that OS fed sheep had higher levels of taurine, l-carnitine, inosine-5'-monophospgate, cholic acid, and taurocholic acid, which are primarily involved in taurine and hypotaurine metabolism, purine metabolism, and bile acid biosynthesis and secretion, decreased fat accumulation and they promote functional or flavor metabolites. OS also increased muscle levels of amino acids that are attributed to better quality and flavorsome mutton. These findings provided further evidence for supplementing sheep with oat grass to improve growth performance and meat quality.
Asunto(s)
Aminoácidos , Avena , Ovinos , Animales , Aminoácidos/análisis , Avena/metabolismo , Cola (estructura animal)/química , Cola (estructura animal)/metabolismo , Composición Corporal , Ácidos Grasos/análisis , Dieta/veterinaria , Músculos/metabolismo , Carne/análisis , Suplementos Dietéticos/análisis , Taurina/metabolismo , Taurina/farmacología , Alimentación Animal/análisisRESUMEN
AIMS: Despite its high concentration in pancreatic islets of Langerhans and broad range of antihyperglycemic effects, the route facilitating the import of dietary taurine into pancreatic ß-cell and mechanisms underlying its insulinotropic activity are unclear. We therefore studied the impact of taurine on beta-cell function, alongside that of other small neutral amino acids, L-alanine and L-proline. MAIN METHODS: Pharmacological profiling of insulin secretion was conducted using clonal BRIN BD11 ß-cells, the impact of taurine on the metabolic fate of glucose carbons was assessed using NMR and the findings were verified by real-time imaging of Ca2+ dynamics in the cytosol of primary mouse and human islet beta-cells. KEY FINDINGS: In our hands, taurine, alanine and proline induced secretory responses that were dependent on the plasma membrane depolarisation, import of Ca2+, homeostasis of K+ and Na+ as well as on cell glycolytic and oxidative metabolism. Taurine shifted the balance between the oxidation and anaplerosis towards the latter, in BRIN BD11 beta-cells. Furthermore, the amino acid signalling was significantly attenuated by inhibition of Na+-K+-Cl- symporter (NKCC). SIGNIFICANCE: These data suggest that taurine, like L-alanine and L-proline, acutely induces glucose-dependent insulin-secretory responses by modulating electrogenic Na+ transport, with potential role of intracellular K+ and Cl- in the signal transduction. The acute action delineated would be consistent with antidiabetic potential of dietary taurine supplementation.
Asunto(s)
Aminoácidos Neutros , Islotes Pancreáticos , Ratones , Animales , Humanos , Insulina/metabolismo , Taurina/farmacología , Taurina/metabolismo , Aminoácidos Neutros/metabolismo , Aminoácidos Neutros/farmacología , Línea Celular , Islotes Pancreáticos/metabolismo , Alanina/farmacología , Alanina/metabolismo , Glucosa/metabolismo , Hipoglucemiantes/farmacología , Prolina/metabolismoRESUMEN
Taurine (TAU), a sulfur-containing amino acid that synthesized from methionine and cystine, plays vital roles in maintenance of redox balance. The effect of substitution of TAU for methionine was evaluated in vivo and in vitro. The effects of replacing methionine with TAU and additional TAU supplementation on the performance and antioxidant capacity of laying hens were evaluated. The in vitro cultured chicken primary hepatocytes and intestinal epithelial cells were further employed. Two hubdred eighty-eight 40-wk-old Isa brown laying hens were divided into 4 groups and subjected one to the following treatments: fed with basal diet with 0.17% crystallized DL-Met (CON), the control diet and replace 25% (21% total Met, 21TAU) or 50% (42% total Met, 42TAU) of crystallized DL-Met with taurine, the control diet supplemented with 0.1% taurine (0.1% TAU). The laying rate, feed intake, egg weight, and feed efficiency were not influenced (P > 0.05) by TAU replacement or additional TAU supplementation. In the liver, 0.1% TAU decreased SOD but increased GSH-Px activity (P < 0.01). In duodenum, 42TAU decreased SOD activity (P < 0.05) while 0.1% TAU decreased GSH level and SOD activity (P < 0.05). In the hepatocytes, TAU treatment decreased (P < 0.05) the MDA and GSH contents, whereas increased SOD and GSH-Px activities (P < 0.05). Meanwhile, TAU treatment decreased (P < 0.05) the protein expression of Nrf2 while increase Keap1 expression. The mRNA expression of Nrf2, SOD1, SOD2, CAT, and GCLC were increased (P < 0.05) and GSR were decreased (P < 0.05) by 0.1% TAU. In the intestinal epithelial cells, TAU treatment decreased (P < 0.05) SOD activity, increased (P < 0.05) CAT activity, and decreased (P < 0.05) the mRNA and protein expression of Nrf2. In summary, partial substitution methionine for taurine (21-42%) has no influence on egg performance of hens. Taurine enhances the antioxidative capacity in hepatocyte but not in the enterocytes and if taurine could offer an improved effect on antioxidant capacity needs to be verified under oxidative stress-challenged conditions.
Asunto(s)
Antioxidantes , Metionina , Animales , Femenino , Antioxidantes/metabolismo , Metionina/farmacología , Metionina/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Taurina/farmacología , Taurina/metabolismo , Pollos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Suplementos Dietéticos/análisis , Dieta/veterinaria , Racemetionina/metabolismo , Superóxido Dismutasa/metabolismo , Alimentación Animal/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Moxibustion is a traditional medical intervention of traditional Chinese medicine. It refers to the direct or indirect application of ignited moxa wool made of mugwort leaves to acupuncture points or other specific parts of the body for either treating or preventing diseases. Moxibustion has been proven to be effective in treating skin lesions of psoriasis. AIM OF THE STUDY: This study was performed to elucidate molecular mechanisms underlying the effects of moxibustion treatment on imiquimod-induced psoriatic mice. MATERIALS AND METHODS: We established an imiquimod (IMQ)-induced psoriatic mice (Model) and assessed the effects of moxibustion (Moxi) treatment on skin lesions of psoriatic mice by the PASI scores and expressions of inflammation-related factors relative to normal control mice (NC). We then performed nuclear magnetic resonance (NMR)-based metabolomic analysis on the skin tissues of the NC, Model and Moxi-treated mice to address metabolic differences among the three groups. RESULTS: Moxi mice showed reduced PASI scores and decreased expressions of the pro-inflammatory cytokines IL-8, IL-17A and IL-23 relative to Model mice. Compared with the Model group, the NC and Moxi groups shared 9 characteristic metabolites and 4 significantly altered metabolic pathways except for taurine and hypotaurine metabolism uniquely identified in the NC group. To a certain extent, moxibustion treatment improved metabolic disorders of skin lesions of psoriatic mice by decreasing glucose, valine, asparagine, aspartate and alanine-mediated cell proliferation and synthesis of scaffold proteins, alleviating histidine-mediated hyperproliferation of blood vessels, and promoting triacylglycerol decomposition. CONCLUSIONS: This study reveals the molecular mechanisms underlying the effects of moxibustion treatment on the skin lesions of psoriasis, potentially improving the clinical efficacy of moxibustion.
Asunto(s)
Moxibustión , Psoriasis , Alanina/metabolismo , Alanina/farmacología , Alanina/uso terapéutico , Animales , Asparagina/metabolismo , Asparagina/farmacología , Asparagina/uso terapéutico , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacología , Ácido Aspártico/uso terapéutico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Glucosa/metabolismo , Histidina/metabolismo , Histidina/farmacología , Histidina/uso terapéutico , Imiquimod , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Interleucina-23/farmacología , Interleucina-23/uso terapéutico , Interleucina-8/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Psoriasis/tratamiento farmacológico , Psoriasis/terapia , Piel , Taurina/metabolismo , Triglicéridos/metabolismo , Valina/metabolismo , Valina/farmacología , Valina/uso terapéuticoRESUMEN
Background: In recent years, a new type of adipose tissue (beige adipose tissue) has been mentioned, unlike white adipose tissue (WAT) and brown adipose tissue (BAT). Beige cells are capable of thermogenesis like BAT. In response to various agents, beige cells can develop within WAT through a process called "browning." Therefore, the prevention of obesity and related diseases by providing WAT browning with new potential agents has been extensively studied in recent years. Taurine has many physiological functions in the body and has beneficial effects on obesity and related metabolic disorders. For this reason, we aimed to investigate whether taurine supplementation has effects on browning of WAT and attenuating obesity. Methods: Thirty-two male C57BL/6 mice were used for the study. Mice were divided into 4 groups as control, control + taurine, high fat diet (HFD) and HFD + taurine, and fed for 20 weeks. Taurine was given in drinking water (5%). Epididymal WAT samples were obtained from mice and RNA was extracted from these tissues. Expression levels of FLCN, mTOR, TFE3, PGC-1α, PGC1-1ß, AMPK, S6K and UCP1 genes were measured by real-time PCR. Results: Taurine supplementation reduced HFD-induced obesity. No UCP1 expression was detected in any of the groups studied. Any of the gene expressions were not significantly different between HFD and HFD + taurine groups. Reduced PGC-1α and PGC-1ß expressions were observed in both HFD and HFD + taurine groups. Conclusions: Taurine reduced the obesity in HFD fed mice, but had no effect on browning of epididymal WAT in this study.
Asunto(s)
Dieta Alta en Grasa , Taurina , Masculino , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Taurina/farmacología , Taurina/metabolismo , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismo , Tejido Adiposo Blanco/metabolismo , Suplementos DietéticosRESUMEN
Abnormal amino acid metabolism in neural cells is involved in the occurrence and development of major depressive disorder. Taurine is an important amino acid required for brain development. Here, microdialysis combined with metabonomic analysis revealed that the level of taurine in the extracellular fluid of the cerebral medial prefrontal cortex (mPFC) was significantly reduced in mice with chronic social defeat stress (CSDS)-induced depression. Therefore, taurine supplementation may be usable an intervention for depression. We found that taurine supplementation effectively rescued immobility time during a tail suspension assay and improved social avoidance behaviors in CSDS mice. Moreover, taurine treatment protected CSDS mice from impairments in dendritic complexity, spine density, and the proportions of different types of spines. The expression of N-methyl D-aspartate receptor subunit 2A, an important synaptic receptor, was largely restored in the mPFC of these mice after taurine supplementation. These results demonstrated that taurine exerted an antidepressive effect by protecting cortical neurons from dendritic spine loss and synaptic protein deficits.
Asunto(s)
Depresión , Trastorno Depresivo Mayor , Ratones , Animales , Espinas Dendríticas/metabolismo , Derrota Social , Trastorno Depresivo Mayor/metabolismo , Taurina/metabolismo , Taurina/farmacología , Neuronas , Aminoácidos/metabolismo , Aminoácidos/farmacología , Estrés Psicológico/metabolismo , Corteza Prefrontal/metabolismo , Ratones Endogámicos C57BLRESUMEN
Carbon tetrachloride (CCl4) is a widely used hepatotoxin for the studies of liver fibrosis and cirrhosis, and taurine has function to abate liver fibrosis induced by CCl4. But the interacting mechanisms between taurine and CCl4 in liver are still largely unknown. These made us to hypothesize that CCl4 may induce liver fibrosis by affecting the expressions of taurine biosynthetic enzymes and taurine synthesis. We thus assayed the expressions of hepatic cysteine dioxygenase (CDO), cysteine sulfonate acid decarboxylase (CSAD) and taurine transporter (TauT) in the progression of mouse liver fibrosis induced by CCl4. The results demonstrated that CCl4 treatment markedly decreased hepatic CSAD, CDO expressions, and taurine levels in hepatic tissue, although TauT expression did not exhibit significant decline. It was contrasting that hepatic α-SMA, serum AST, ALT, ALP kept increasing, which were accompanied by the pathological characters of liver, whereas taurine supplement attenuated the progression of liver fibrosis induced by CCl4. These results demonstrate that CCl4 may induce liver fibrosis by inhibiting hepatic CSAD and CDO expressions and taurine synthesis, which are crucial for our understanding the mechanisms of liver fibrosis induced by CCl4, and also potential for establishing therapeutic strategies of liver fibrosis and related diseases.