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Sample records for hepatic taurine transport

  1. Involvement of γ-aminobutyric acid transporter 2 in the hepatic uptake of taurine in rats.

    PubMed

    Ikeda, Saori; Tachikawa, Masanori; Akanuma, Shin-ichi; Fujinawa, Jun; Hosoya, Ken-ichi

    2012-08-01

    Taurine is essential for the hepatic synthesis of bile salts and, although taurine is synthesized mainly in pericentral hepatocytes, taurine and taurine-conjugated bile acids are abundant in periportal hepatocytes. One possible explanation for this discrepancy is that the active supply of taurine to hepatocytes from the blood stream is a key regulatory factor. The purpose of the present study is to investigate and identify the transporter responsible for taurine uptake by periportal hepatocytes. An in vivo bolus injection of [(3)H]taurine into the rat portal vein demonstrated that 25% of the injected [(3)H]taurine was taken up by the liver on a single pass. The in vivo uptake was significantly inhibited by GABA, taurine, β-alanine, and nipecotic acid, a GABA transporter (GAT) inhibitor, each at a concentration of 10 mM. The characteristics of Na(+)- and Cl(-)-dependent [(3)H]taurine uptake by freshly isolated rat hepatocytes were consistent with those of GAT2 (solute carrier SLC6A13). Indeed, the K(m) value of the saturable uptake (594 μM) was close to that of mouse SLC6A13-mediated taurine transport. Although GABA, taurine, and β-alanine inhibited the [(3)H]taurine uptake by > 50%, each at a concentration of 10 mM, GABA caused a marked inhibition with an IC(50) value of 95 μM. The [(3)H]taurine uptake exhibited a significant reduction when the GAT2 gene was silenced. Immunohistochemical analysis showed that GAT2 was localized on the sinusoidal membrane of the hepatocytes predominantly in the periportal region. These results suggest that GAT2 is responsible for taurine transport from the circulating blood to hepatocytes predominantly in the periportal region.

  2. Hepatic taurine transport: a Na/sup +/-dependent carrier on the basolateral plasma membrane

    SciTech Connect

    Bucuvalas, J.C.; Goodrich, A.L.; Suchy, F.J.

    1987-09-01

    Highly purified rat basolateral liver plasma membrane vesicles were used examine the mechanism and the driving forces for hepatic uptake of the ..beta..-amino acid, taurine. An inwardly directed 100 mM NaCl gradient stimulated the initial rate of taurine uptake and energized a transient twofold accumulation of taurine above equilibrium (overshoot). In contrast, uptake was slower and no overshoot was detected in the presence of a KCl gradient. A negative intravesicular electrical potential generated by the presence of permeant anions or an outwardly directed K/sup +/ gradient with valinomycin increased Na/sup +/-stimulated taurine uptake. External Cl/sup -/ stimulated Na/sup +/-dependent taurine uptake independent of effects on the transmembrane electrical potential difference. Na/sup +/-dependent taurine uptake showed a sigmoidal dependence on extravesicular Na/sup +/ concentration, suggesting multiple Na/sup +/ ions are involved in the translocation of each taurine molecule. Na/sup +/-dependent taurine uptake demonstrated Michaelis-Menten kinetics with a maximum velocity of 0.537 nmol x mg protein/sup -1/ x min/sup -1/ and an apparent K/sub m/ of 174 ..mu..M. (/sup 3/H)taurine uptake was inhibited by the presence of excess unlabeled taurine, ..beta..-alanine, or hypotaurine but not by L-glutamine or L-alanine. In summary, using basolateral liver plasma membrane vesicles, the authors have shown that hepatic uptake of taurine occurs by a carrier-mediated, secondary active transport process specific for ..beta..-amino acids. Uptake is electrogenic, stimulated by external Cl/sup -/, and requires multiple Na/sup +/ ions for the translocation of each taurine molecule.

  3. Choroid plexus taurine transport.

    PubMed

    Keep, R F; Xiang, J

    1996-04-09

    The putative osmoregulatory agent, taurine, is lost from the brain during hypo-osmotic stress or ischemia, but the regulatory mechanisms involved in this loss have not been fully elucidated. In this study, we have examined taurine transport by the isolated rat choroid plexus, one element of the brain-blood interface, and examined how it may be regulated as part of brain volume regulation. Choroid plexus taurine uptake was Na- and Cl-dependent with a Vmax and Km of 6.5 +/- 0.3 pmol/mg/min and 232 +/- 33 microM. The latter is substantially greater than the normal CSF taurine concentration and this may be important in removing taurine released into the CSF during parenchymal cell swelling. Taurine uptake also appears calmodulin dependent as it was reduced by 84 and 91% in the presence of 25 microM trifluoperazine and 100 microM W-7, two calmodulin inhibitors. Taurine efflux from choroid plexus was stimulated by trifluoperazine, taurine, and hypo-osmotic stress. The latter two effects were reduced by niflumic acid, suggesting that taurine and hypo-osmotic stress act on the same pathway. The stimulation of efflux by hypo-osmotic stress decreased with time, whereas the effect of external taurine was sustained. If this efflux pathway is involved in the movement of taurine from choroid plexus to blood, these results suggest that changes in extracellular taurine may be more important than the direct effect of hypo-osmolality in the long-term loss of taurine from the brain.

  4. Phenotype of the taurine transporter knockout mouse.

    PubMed

    Warskulat, Ulrich; Heller-Stilb, Birgit; Oermann, Evelyn; Zilles, Karl; Haas, Helmut; Lang, Florian; Häussinger, Dieter

    2007-01-01

    This chapter reports present knowledge on the properties of mice with disrupted gene coding for the taurine transporter (taut-/- mice). Study of those mice unraveled some of the roles of taurine and its membrane transport for the development and maintenance of normal organ functions and morphology. When compared with wild-type controls, taut-/- mice have decreased taurine levels in skeletal and heart muscle by about 98%, in brain, kidney, plasma, and retina by 80 to 90%, and in liver by about 70%. taut-/- mice exhibit a lower body mass as well as a strongly reduced exercise capacity compared with taut+/- and wild-type mice. Furthermore, taut-/- mice show a variety of pathological features, for example, subtle derangement of renal osmoregulation, changes in neuroreceptor expression, and loss of long-term potentiation in the striatum, and they develop clinically relevant age-dependent disorders, for example, visual, auditory, and olfactory dysfunctions, unspecific hepatitis, and liver fibrosis. Taurine-deficient animal models such as acutely dietary-manipulated foxes and cats, pharmacologically induced taurine-deficient rats, and taurine transporter knockout mouse are powerful tools allowing identification of the mechanisms and complexities of diseases mediated by impaired taurine transport and taurine depletion (Chapman et al., 1993; Heller-Stilb et al., 2002; Huxtable, 1992; Lake, 1993; Moise et al., 1991; Novotny et al., 1991; Pion et al., 1987; Timbrell et al., 1995; Warskulat et al., 2004, 2006b). Taurine, which is the most abundant amino acid in many tissues, is normally found in intracellular concentrations of 10 to 70 mmol/kg in mammalian heart, brain, skeletal muscle, liver, and retina (Chapman et al., 1993; Green et al., 1991; Huxable, 1992; Timbrell et al., 1995). These high taurine levels are maintained by an ubiquitous expression of Na(+)-dependent taurine transporter (TAUT) in the plasma membrane (Burg, 1995; Kwon and Handler, 1995; Lang et al., 1998

  5. Physiological significance of taurine and the taurine transporter in intestinal epithelial cells.

    PubMed

    Shimizu, M; Satsu, H

    2000-01-01

    Taurine transport in human intestinal epithelial Caco-2 cells was down-regulated by culturing the cells in taurine-containing media and was up-regulated in a taurine-free medium. This adaptive regulation was associated with changes in both the Vmax and Km values of taurine transport. A change in the mRNA level of the taurine transporter (TAUT) in this regulation was also observed. The presence of such a regulatory mechanism for maintaining the intracellular taurine content at a certain level suggests that taurine plays an important role in the intestinal cell functions. The intracellular taurine content was increased when Caco-2 cells were exposed to a hypertonic stress. TAUT was up-regulated via the increased expression of TAUT mRNA in the hypertonic cells, suggesting that taurine serves as an osmolyte and protects the cells from osmotic stress. Similar up-regulation of TAUT was observed in the small intestine of water-deprived rats.

  6. Taurine-Induced Long-Lasting Enhancement of Synaptic Transmission in Mice: Role of Transporters

    PubMed Central

    Sergeeva, O A; Chepkova, A N; Doreulee, N; Eriksson, K S; Poelchen, W; Mönnighoff, I; Heller-Stilb, B; Warskulat, U; Häussinger, D; Haas, H L

    2003-01-01

    Taurine, a major osmolyte in the brain evokes a long-lasting enhancement (LLETAU) of synaptic transmission in hippocampal and cortico-striatal slices. Hippocampal LLETAU was abolished by the GABA uptake blocker nipecotic acid (NPA) but not by the taurine-uptake inhibitor guanidinoethyl sulphonate (GES). Striatal LLETAU was sensitive to GES but not to NPA. Semiquantitative PCR analysis and immunohistochemistry revealed that taurine transporter expression is significantly higher in the striatum than in the hippocampus. Taurine transporter-deficient mice displayed very low taurine levels in both structures and a low ability to develop LLETAU in the striatum, but not in the hippocampus. The different mechanisms of taurine-induced synaptic plasticity may reflect the different vulnerabilities of these brain regions under pathological conditions that are accompanied by osmotic changes such as hepatic encephalopathy. PMID:12824447

  7. GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition.

    PubMed

    Sergeeva, O A; Fleischer, W; Chepkova, A N; Warskulat, U; Häussinger, D; Siebler, M; Haas, H L

    2007-12-01

    The Striatum is involved in the regulation of movements and motor skills. We have shown previously, that the osmolyte and neuromodulator taurine plays a role in striatal plasticity. We demonstrate now that hereditary taurine deficiency in taurine-transporter knock-out (TAUT KO) mice results in disinhibition of striatal network activity, which can be corrected by taurine supplementation. Modification of GABAA but not glycine receptors (taurine is a ligand for both receptor types) underlies this disinhibition. Whole-cell recordings from acutely isolated as well as cultured striatal neurons revealed a decreased agonist sensitivity of the GABAA receptor in TAUT KO neurons in the absence of changes in the maximal GABA-evoked current amplitude. The striatal GABA level in TAUT KO mice was unchanged. The amplitude enhancement of spontaneous IPSCs by zolpidem was stronger in TAUT KO than in wild-type (WT) animals. Tonic inhibition was absent in striatal neurons under control conditions but was detected after incubation with the GABA-transaminase inhibitor vigabatrin: bicuculline induced a larger shift of baseline current in WT as compared to TAUT KO neurons. Lack of taurine leads to reduced sensitivity of synaptic and extrasynaptic GABAA receptors and consequently to disinhibition. These findings help in understanding neuropathologies accompanied by the loss of endogenous taurine, for instance in hepatic encephalopathy.

  8. Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy.

    PubMed

    Ito, Takashi; Kimura, Yasushi; Uozumi, Yoriko; Takai, Mika; Muraoka, Satoko; Matsuda, Takahisa; Ueki, Kei; Yoshiyama, Minoru; Ikawa, Masahito; Okabe, Masaru; Schaffer, Stephen W; Fujio, Yasushi; Azuma, Junichi

    2008-05-01

    The sulfur-containing beta-amino acid, taurine, is the most abundant free amino acid in cardiac and skeletal muscle. Although its physiological function has not been established, it is thought to play an important role in ion movement, calcium handling, osmoregulation and cytoprotection. To begin examining the physiological function of taurine, we generated taurine transporter- (TauT-) knockout mice (TauTKO), which exhibited a deficiency in myocardial and skeletal muscle taurine content compared with their wild-type littermates. The TauTKO heart underwent ventricular remodeling, characterized by reductions in ventricular wall thickness and cardiac atrophy accompanied with the smaller cardiomyocytes. Associated with the structural changes in the heart was a reduction in cardiac output and increased expression of heart cardiac failure (fetal) marker genes, such as ANP, BNP and beta-MHC. Moreover, ultrastructural damage to the myofilaments and mitochondria was observed. Further, the skeletal muscle of the TauTKO mice also exhibited decreased cell volume, structural defects and a reduction of exercise endurance capacity. Importantly, the expression of Hsp70, ATA2 and S100A4, which are upregulated by osmotic stress, was elevated in both heart and skeletal muscle of the TauTKO mice. Taurine depletion causes cardiomyocyte atrophy, mitochondrial and myofiber damage and cardiac dysfunction, effects likely related to the actions of taurine. Our data suggest that multiple actions of taurine, including osmoregulation, regulation of mitochondrial protein expression and inhibition of apoptosis, collectively ensure proper maintenance of cardiac and skeletal muscular structure and function.

  9. The taurine transporter substrate guanidinoethyl sulfonate mimics the action of taurine on long-term synaptic potentiation.

    PubMed

    Suárez, Luz M; Muñoz, María-Dolores; González, José C; Bustamante, Julián; Del Río, Rafael Martín; Solís, José M

    2016-11-01

    Taurine is especially abundant in rodent brain where it appears to be involved in osmoregulation and synaptic plasticity mechanisms. The demonstration of a physiological role for taurine has been hampered by the difficulty in modifying taurine levels in most tissues, including the brain. We used an experimental strategy to reduce taurine levels, involving treatment with guanidinoethyl sulfonate (GES), a structural analogue of taurine that, among other properties, acts as a competitive inhibitor of taurine transport. GES delivered in the drinking water of rats for 1 month effectively reduced taurine levels in brain structures (hippocampus, cerebellum and cortex) and outside the brain (heart, muscle, kidney, liver and plasma) by between 50 and 80 %, depending on the tissue. This partial taurine depletion did not affect either basal synaptic transmission or the late phase of long-term potentiation (late-LTP) in hippocampal slices. In vivo microdialysis studies in the hippocampus revealed that GES treatment reduced extracellular taurine levels and the magnitude of taurine released in response to the application of either N-methyl-D-aspartate (NMDA) or a hypoosmotic solution, without affecting release mechanisms. Finally, we demonstrated in hippocampal slices that a brief GES application can mimic taurine action on the conversion of a decremental LTP into a perdurable late-LTP, concluding that GES might replace taurine function in some mechanisms such as those implicated in synaptic plasticity.

  10. Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum.

    PubMed

    Yu, Yan-Rong; Ni, Xian-Qiang; Huang, Jie; Zhu, Yong-Hong; Qi, Yong-Fen

    2016-04-01

    In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4(+) Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response.

  11. Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum

    PubMed Central

    Yu, Yan-Rong; Ni, Xian-Qiang; Huang, Jie; Zhu, Yong-Hong; Qi, Yong-Fen

    2016-01-01

    In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4+ Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response. PMID:27054062

  12. Taurine deficiency, synthesis and transport in the mdx mouse model for Duchenne Muscular Dystrophy.

    PubMed

    Terrill, Jessica R; Grounds, Miranda D; Arthur, Peter G

    2015-09-01

    The amino acid taurine is essential for the function of skeletal muscle and administration is proposed as a treatment for Duchenne Muscular Dystrophy (DMD). Taurine homeostasis is dependent on multiple processes including absorption of taurine from food, endogenous synthesis from cysteine and reabsorption in the kidney. This study investigates the cause of reported taurine deficiency in the dystrophic mdx mouse model of DMD. Levels of metabolites (taurine, cysteine, cysteine sulfinate and hypotaurine) and proteins (taurine transporter [TauT], cysteine deoxygenase and cysteine sulfinate dehydrogenase) were quantified in juvenile control C57 and dystrophic mdx mice aged 18 days, 4 and 6 weeks. In C57 mice, taurine content was much higher in both liver and plasma at 18 days, and both cysteine and cysteine deoxygenase were increased. As taurine levels decreased in maturing C57 mice, there was increased transport (reabsorption) of taurine in the kidney and muscle. In mdx mice, taurine and cysteine levels were much lower in liver and plasma at 18 days, and in muscle cysteine was low at 18 days, whereas taurine was lower at 4: these changes were associated with perturbations in taurine transport in liver, kidney and muscle and altered metabolism in liver and kidney. These data suggest that the maintenance of adequate body taurine relies on sufficient dietary intake of taurine and cysteine availability and metabolism, as well as retention of taurine by the kidney. This research indicates dystrophin deficiency not only perturbs taurine metabolism in the muscle but also affects taurine metabolism in the liver and kidney, and supports targeting cysteine and taurine deficiency as a potential therapy for DMD. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  13. Myogenic differentiation induces taurine transporter in association with taurine-mediated cytoprotection in skeletal muscles.

    PubMed

    Uozumi, Yoriko; Ito, Takashi; Hoshino, Yuki; Mohri, Tomomi; Maeda, Makiko; Takahashi, Kyoko; Fujio, Yasushi; Azuma, Junichi

    2006-03-15

    Skeletal muscle homoeostasis is maintained by a variety of cytoprotective mechanisms. Since ablation of the TauT (taurine transporter) gene results in susceptibility to exercise-induced muscle weakness in vivo, it has been suggested that TauT is essential for skeletal muscle function. However, the regulatory mechanisms of TauT expression remain to be elucidated. In the present study, we demonstrated that TauT was up-regulated during myogenesis in C2C12 cells. Treatment with bFGF (basic fibroblast growth factor), which inhibited muscle differentiation, abrogated myogenic induction of TauT. The promoter activities of TauT were up-regulated during muscle differentiation in C2C12 cells. Database analyses identified an MEF2 (myocyte enhancer binding factor 2) consensus sequence at -844 in the rat TauT gene. Truncation of the promoter region containing the MEF2 site significantly reduced the promoter activity, demonstrating the functional importance of the MEF2 site. Electrophoretic mobility-shift assays confirmed that MEF2 bound to the MEF2 consensus sequence and that DNA-protein complex levels were increased during differentiation. Promoter analyses using mutated promoter-reporter plasmids demonstrated that this site was functional. Importantly, transfection with a MyoD expression vector markedly enhanced TauT promoter activity in the (non-myogenic) 10T1/2 cells. Moreover, co-transfection with an MEF2 expression vector augmented MyoD-induced TauT promoter activity, suggesting that MEF2 is required for full activation of TauT expression. Finally, we examined the effects of taurine on myotube atrophy to clarify the biological significance of the up-regulation of TauT, and demonstrated that taurine attenuated muscle atrophy induced by dexamethasone. TauT expression is regulated under the control of the myogenic programme, and we propose that this is the mechanism for taurine-mediated resistance to muscle atrophy.

  14. Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised.

    PubMed

    Warskulat, Ulrich; Flögel, Ulrich; Jacoby, Christoph; Hartwig, Hans-Georg; Thewissen, Michael; Merx, Marc W; Molojavyi, Andrej; Heller-Stilb, Birgit; Schrader, Jürgen; Häussinger, Dieter

    2004-03-01

    Taurine is the most abundant free amino acid in heart and skeletal muscle. In the present study, the effects of hereditary taurine deficiency on muscle function were examined in taurine transporter knockout (taut-/-) mice. These mice show an almost complete depletion of heart and skeletal muscle taurine levels. Treadmill experiments demonstrated that total exercise capacity of taut-/- mice was reduced by >80% compared with wild-type controls. The decreased performance of taut-/- mice correlated with increased lactate levels in serum during exercise. Surprisingly, cardiac function of taut-/- mice as assessed by magnetic resonance imaging, echocardiography, and isolated heart studies showed a largely normal phenotype under both control and stimulated conditions. However, analysis of taut-/- skeletal muscle revealed electromyographic abnormalities. (1)H nuclear magnetic resonance spectroscopy of tissue extracts showed that in the heart of taut-/- mice the lack of taurine was compensated by the up-regulation of various organic solutes. In contrast, a deficit of >10 mM in total organic osmolyte concentration was found in skeletal muscle. The present study identifies taurine transport as a crucial factor for the maintenance of skeletal muscle function and total exercise capacity, while cardiac muscle apparently can compensate for the loss of taurine.

  15. Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo

    PubMed Central

    Jurkowska, Halina; Niewiadomski, Julie; Hirschberger, Lawrence L.; Roman, Heather B.; Mazor, Kevin M.; Liu, Xiaojing; Locasale, Jason W.; Park, Eunkyue

    2016-01-01

    The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated in liver of Cdo1-null and Csad-null mice and lowered to wild-type levels by dietary taurine supplementation. The mechanism by which taurine status affects hepatic CSAD and BHMT expression appears to be complex and to require factors outside of hepatocytes. Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation. PMID:26481005

  16. Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo.

    PubMed

    Jurkowska, Halina; Niewiadomski, Julie; Hirschberger, Lawrence L; Roman, Heather B; Mazor, Kevin M; Liu, Xiaojing; Locasale, Jason W; Park, Eunkyue; Stipanuk, Martha H

    2016-03-01

    The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated in liver of Cdo1-null and Csad-null mice and lowered to wild-type levels by dietary taurine supplementation. The mechanism by which taurine status affects hepatic CSAD and BHMT expression appears to be complex and to require factors outside of hepatocytes. Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation.

  17. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    PubMed Central

    2010-01-01

    Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells), as in vitro blood-placental barrier (BPB) model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC) activator in TR-TBT cells. Also, calcium ion (Ca2+) was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α), lipopolysaccharide (LPS) and diethyl maleate (DEM) significantly increased taurine uptake, but H2O2 and nitric oxide (NO) donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus. PMID:20804613

  18. Changes in taurine as an indicator of hepatic dysfunction and biochemical perturbations. Studies in vivo and in vitro.

    PubMed

    Timbrell, J A; Waterfield, C J

    1996-01-01

    We have shown that urinary taurine level may be used as a biomarker of pathological and biochemical lesions. Detection of changes in the urinary concentration of this low molecular weight metabolite indicates biochemical lesions which may also be associated with pathological damage. Hepatotoxic compounds such as CCl4, galactosamine and thioacetamide that cause hepatic necrosis and compounds such as hydrazine and ethionine that cause fatty liver all result in elevated urinary taurine levels in rats. However compounds which do not cause liver damage, such as cycloheximide, also raise urinary taurine levels. All of these substances are known to or are believed to inhibit protein synthesis. Conversely, compounds which increase protein synthesis, such as phenobarbital and clenbuterol, significantly decrease urinary taurine levels. Compounds which interfere with hepatic GSH synthesis will also change urinary taurine levels. Thus, depletion of GSH with diethyl maleate or phorone decreases urinary taurine whereas inhibition of GSH synthesis with compounds such as buthionine sulphoximine increases urinary taurine levels. In isolated hepatocytes in vitro, leakage of taurine occurs in response to cytotoxic compounds such as hydrazine and allyl alcohol. However, total taurine levels were increased by the hepatotoxicant CCl4. Taurine synthesis is decreased by depletion of GSH with allyl alcohol in isolated hepatocytes. Therefore taurine levels are an important potential biomarker for biochemical lesions induced by chemicals both in vivo and in vitro, in particular changes in protein and GSH synthesis.

  19. Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice.

    PubMed

    Ito, Takashi; Oishi, Shohei; Takai, Mika; Kimura, Yasushi; Uozumi, Yoriko; Fujio, Yasushi; Schaffer, Stephen W; Azuma, Junichi

    2010-08-24

    Taurine, a sulfur-containing beta-amino acid, is highly contained in heart and skeletal muscle. Taurine has a variety of biological actions, such as ion movement, calcium handling and cytoprotection in the cardiac and skeletal muscles. Meanwhile, taurine deficiency leads various pathologies, including dilated cardiomyopathy, in cat and fox. However, the essential role of taurine depletion on pathogenesis has not been fully clarified. To address the physiological role of taurine in mammalian tissues, taurine transporter-(TauT-) knockout models were recently generated. TauTKO mice exhibited loss of body weight, abnormal cardiac function and the reduced exercise capacity with tissue taurine depletion. In this chapter, we summarize pathological profile and histological feature of heart and skeletal muscle in TauTKO mice.

  20. Osmoregulated taurine transport in H4IIE hepatoma cells and perfused rat liver.

    PubMed Central

    Warskulat, U; Wettstein, M; Häussinger, D

    1997-01-01

    The effects of aniso-osmotic exposure on taurine transport were studied in H4IIE rat hepatoma cells. Hyperosmotic (405 mosmol/l) exposure of H4IIE cells stimulated Na+-dependent taurine uptake and led to an increase in taurine transporter (TAUT) mRNA levels, whereas hypo-osmotic (205 mosmol/l) exposure diminished both taurine uptake and TAUT mRNA levels when compared with normo-osmotic (305 mosmol/l) control incubations. Taurine uptake increased 30-40-fold upon raising the ambient osmolarity from 205 to 405 mosmol/l. When H4IIE cells and perfused livers were preloaded with taurine, hypo-osmotic cell swelling led to a rapid release of taurine from the cells. The taurine efflux, but not taurine uptake, was sensitive to 4,4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS), suggestive of an involvement of DIDS-sensitive channels in mediating volume-regulatory taurine efflux. Whereas in both H4IIE rat hepatoma cells and primary hepatocytes TAUT mRNA levels were strongly dependent upon ambient osmolarity, mRNAs for other osmolyte transporters, i.e. the betaine transporter BGT-1 and the Na+/myo-inositol transporter SMIT, were not detectable. In line with this, myo-inositol uptake by H4IIE hepatoma cells was low and was not stimulated by hyperosmolarity. However, despite the absence of BGT-1 mRNA, a slight osmosensitive uptake of betaine was observed, but the rate was less than 10% of that of taurine transport. This study identifies a constitutively expressed and osmosensitive TAUT in H4IIE cells and the use of taurine as a main osmolyte, whereas betaine and myo-inositol play little or no role in the osmolyte strategy in these cells. This is in contrast with rat liver macrophages, in which betaine has been shown to be a major osmolyte. PMID:9032454

  1. Cloning, tissue and ontogenetic expression of the taurine transporter in the flatfish Senegalese sole (Solea senegalensis).

    PubMed

    Pinto, Wilson; Rønnestad, Ivar; Jordal, Ann-Elise Olderbakk; Gomes, Ana S; Dinis, Maria Teresa; Aragão, Cláudia

    2012-04-01

    Flatfish species seem to require dietary taurine for normal growth and development. Although dietary taurine supplementation has been recommended for flatfish, little is known about the mechanisms of taurine absorption in the digestive tract of flatfish throughout ontogeny. This study described the cloning and ontogenetic expression of the taurine transporter (TauT) in the flatfish Senegalese sole (Solea senegalensis). Results showed a high similarity between TauT in Senegalese sole and other vertebrates, but a change in TauT amino acid sequences indicates that taurine transport may differ between mammals and fish, reptiles or birds. Moreover, results showed that Senegalese sole metamorphosis is an important developmental trigger to promote taurine transport in larvae, especially in muscle tissues, which may be important for larval growth. Results also indicated that the capacity to uptake dietary taurine in the digestive tract is already established in larvae at the onset of metamorphosis. In Senegalese sole juveniles, TauT expression was highest in brain, heart and eye. These are organs where taurine is usually found in high concentrations and is believed to play important biological roles. In the digestive tract of juveniles, TauT was more expressed in stomach and hindgut, indicating that dietary taurine is quickly absorbed when digestion begins and taurine endogenously used for bile salt conjugation may be recycled at the posterior end of the digestive tract. Therefore, these results suggest an enterohepatic recycling pathway for taurine in Senegalese sole, a process that may be important for maintenance of the taurine body levels in flatfish species.

  2. Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood-Retinal Barrier and in the Liver.

    PubMed

    Kubo, Yoshiyuki; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

    2016-01-01

    Cumulative studies showed that taurine (2-aminoethanesulfonic acid) contributes to a variety of physiological events. Transport study suggested the cellular taurine transport in an Na(+)- and Cl(-)-dependent manner, and the several members of SLC6A family have been shown as taurine transporter. At the inner blood-retinal barrier (BRB), taurine transporter (TauT/SLC6A) is involved in the transport of taurine to the retina from the circulating blood. The involvement of TauT is also suggested in γ-aminobutyric acid (GABA) transport at the inner BRB, and its role is assumed in the elimination of GABA from the retinal interstitial fluid. In the retina, taurine is thought to be a major organic osmolyte, and its influx and efflux through TauT and volume-sensitive organic osmolyte and anion channel (VSOAC) in Müller cells regulate the osmolarity in the retinal microenvironment to maintain a healthy retina. In the liver, hepatocytes take up taurine via GABA transporter 2 (GAT2/SLC6A13, the orthologue of mouse GAT3) expressed at the sinusoidal membrane of periportal hepatocytes, contributing to the metabolism of bile acid. Site-directed mutagenesis study suggests amino acid residues that are crucial in the recognition of substrates by GATs and TauT. The evidence suggests the physiological impact of taurine transporters in tissues.

  3. Sulfasalazine-induced renal and hepatic injury in rats and the protective role of taurine

    PubMed Central

    Heidari, Reza; Rasti, Maryam; Shirazi Yeganeh, Babak; Niknahad, Hossein; Saeedi, Arastoo; Najibi, Asma

    2016-01-01

    Introduction: Sulfasalazine is a drug commonly administrated against inflammatory-based disorders. On the other hand, kidney and liver injury are serious adverse events accompanied by sulfasalazine administration. No specific therapeutic option is available against this complication. The current investigation was designed to evaluate the potential protective effects of taurine against sulfasalazine-induced kidney and liver injury in rats. Methods: Male Sprague-Dawley rats were administered with sulfasalazine (600 mg/kg, oral) for 14 consecutive days. Animals received different doses of taurine (250, 500 and 1000 mg/ kg, i.p.) every day. Markers of organ injury were evaluated on day 15th, 24 h after the last dose of sulfasalazine. Results: Sulfasalazine caused renal and hepatic injury as judged by an increase in serum level of creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP). The levels of reactive oxygen species (ROS) and lipid peroxidation were raised in kidney and liver of sulfasalazine-treated animals. Moreover, tissue glutathione reservoirs were depleted after sulfasalazine administration. Histopathological changes of kidney and liver also endorsed organ injury. Taurine administration (250, 500 and 1000 mg/kg/day, i.p) alleviated sulfasalazine-induced renal and hepatic damage. Conclusion: Taurine administration could serve as a potential protective agent with therapeutic capabilities against sulfasalazine adverse effects. PMID:27340618

  4. Zinc and zinc chelators modify taurine transport in rat retinal cells.

    PubMed

    Márquez, Asarí; Urbina, Mary; Lima, Lucimey

    2014-11-01

    Zinc regulates Na(+)/Cl(-)-dependent transporters, similar to taurine one, such as those for dopamine, serotonin and norepinephrine. This study examined the ex vivo effect of zinc (ZnSO4), N,N,N,N-tetraquis-(2-piridilmetil)etilendiamino (TPEN) and diethylenetriaminepenta-acetic acid (DTPA), intracellular and extracellular zinc chelators, respectively, on rat retina [(3)H]taurine transport. Isolated cells were incubated in Locke solution with 100 nM of [(3)H]taurine for 25 s. Different concentrations of ZnSO4 (0.5-200 μM) were used. Low concentrations of ZnSO4 (30 and 40 μM) increased the transport, while higher concentrations (100, 150 and 200 μM) decreased it. Various concentrations of TPEN (1-200 μM) were added. Intermediate concentrations of TPEN (10-60 μM) significantly decreased [(3)H]taurine transport. The presence of TPEN, 20 μM, plus ZnSO4 reversed the effect of TPEN alone. Several concentrations of DTPA (1-500 μM) were also investigated. Reduction of transport took place at high concentrations of the chelator (100, 250 and 500 μM). DTPA, 500 μM, plus ZnSO4, did not modify the effect of it. These results indicate that zinc modulates taurine transport in a concentration-dependent manner, directly acting on the transporter or by forming taurine-zinc complexes in cell membranes.

  5. The effect of taurine and β-alanine supplementation on taurine transporter protein and fatigue resistance in skeletal muscle from mdx mice.

    PubMed

    Horvath, Deanna M; Murphy, Robyn M; Mollica, Janelle P; Hayes, Alan; Goodman, Craig A

    2016-11-01

    This study investigated the effect of taurine and β-alanine supplementation on muscle function and muscle taurine transporter (TauT) protein expression in mdx mice. Wild-type (WT) and mdx mice (5 months) were supplemented with taurine or β-alanine for 4 weeks, after which in vitro contractile properties, fatigue resistance and force recovery, and the expression of the TauT protein and proteins involved in excitation-contraction (E-C) coupling were examined in fast-twitch muscle. There was no difference in basal TauT protein expression or basal taurine content between mdx than WT muscle. Supplementation with taurine and β-alanine increased and reduced taurine content, respectively, in muscle from WT and mdx mice but had no effect of TauT protein. Taurine supplementation reduced body and muscle mass, and enhanced fatigue resistance and force recovery in mdx muscle. β-Alanine supplementation enhanced fatigue resistance in WT and mdx muscle. There was no difference in the basal expression of key E-C coupling proteins [ryanodine receptor 1 (RyR1), dihydropyridine receptor (DHPR), sarco(endo)plasmic reticulum Ca(2+)-ATPase 1 (SERCA1) or calsequestrin 1 (CSQ1)] between WT and mdx mice, and the expression of these proteins was not altered by taurine or β-alanine supplementation. These findings suggest that TauT protein expression is relatively insensitive to changes in muscle taurine content in WT and mdx mice, and that taurine and β-alanine supplementation may be viable therapeutic strategies to improve fatigue resistance of dystrophic skeletal muscle.

  6. Characterization of a carrier-mediated transport system for taurine in the fetal mouse heart in vitro.

    PubMed

    Grosso, D S; Roeske, W R; Bressler, R

    1978-04-01

    Cardiac taurine levels are elevated in hypertension and congestive heart failure. A possible mechanism for this increase in taurine is an alteration of its uptake. We sought to identify and characterize a carrier-mediated transport system for taurine in the mammalian myocardium utilizing the fetal mouse heart in organ culture. Hearts from fetuses of 16-19 days gestational age used in these studies had an endogenous taurine content of 14.1+/-0.5 nmol/mg tissue. The uptake of [(3)H]taurine was linear for up to 8 h. Taurine was accumulated against a concentration gradient as demonstrated by a net increase in taurine concentration when hearts were incubated in 0.5 mM taurine. [(3)H]Taurine uptake was saturable, K(m) = 0.44 mM, temperature dependent, and required sodium. The close structural analogues, hypotaurine and beta-alanine, reduced [(3)H]taurine uptake by 87% when present in 100-fold excess. The alpha-amino acids alanine, alpha-aminoisobutyric acid, glycine, leucine, and threonine did not inhibit uptake. Other taurine analogues tested were guanidinotaurine, guanidinopropionic acid, gamma-aminobutyric acid, 2-aminoethane phosphonic acid, aminomethane sulfonic acid, 3-aminopropane sulfonic acid, N-acetyltaurine, and isethionic acid. We conclude that a carrier-mediated transport system for taurine exists in the fetal mouse heart based on the demonstration of (a) temperature dependence, (b) saturability, and (c) structural selectivity of the uptake process. Transport was demonstrated to be mediated by a beta-amino acid uptake system. In addition, taurine uptake was observed to be sodium dependent, energy dependent, and capable of accumulating taurine against a concentration gradient.

  7. Taurine transport in human placental trophoblast is important for regulation of cell differentiation and survival.

    PubMed

    Desforges, M; Parsons, L; Westwood, M; Sibley, C P; Greenwood, S L

    2013-03-21

    The outer epithelial cell layer of human placenta, the syncytiotrophoblast, is a specialised terminally differentiated multinucleate tissue. It is generated and renewed from underlying cytotrophoblast cells that undergo proliferation, differentiation and fusion with syncytiotrophoblast. Acquisition of fresh cellular components is thought to be balanced by apoptosis and shedding of aged nuclei. This process of trophoblast cell turnover maintains a functional syncytiotrophoblast, capable of sufficient nutrient transfer from mother to foetus. Foetal growth restriction (FGR) is a pregnancy complication associated with aberrant trophoblast turnover and reduced activity of certain amino acid transporters, including the taurine transporter (TauT). Taurine is the most abundant amino acid in human placenta implying an important physiological role within this tissue. Unlike other amino acids, taurine is not incorporated into proteins and in non-placental cell types represents an important osmolyte involved in cell volume regulation, and is also cytoprotective. Here, we investigated the role of taurine in trophoblast turnover using RNA interference to deplete primary human trophoblast cells of TauT and reduce intracellular taurine content. Trophoblast differentiation was compromised in TauT-deficient cells, and susceptibility of these cells to an inflammatory cytokine that is elevated in FGR was increased, evidenced by elevated levels of apoptosis. These data suggest an important role for taurine in trophoblast turnover and cytoprotection.

  8. Taurine transport in human placental trophoblast is important for regulation of cell differentiation and survival

    PubMed Central

    Desforges, M; Parsons, L; Westwood, M; Sibley, C P; Greenwood, S L

    2013-01-01

    The outer epithelial cell layer of human placenta, the syncytiotrophoblast, is a specialised terminally differentiated multinucleate tissue. It is generated and renewed from underlying cytotrophoblast cells that undergo proliferation, differentiation and fusion with syncytiotrophoblast. Acquisition of fresh cellular components is thought to be balanced by apoptosis and shedding of aged nuclei. This process of trophoblast cell turnover maintains a functional syncytiotrophoblast, capable of sufficient nutrient transfer from mother to foetus. Foetal growth restriction (FGR) is a pregnancy complication associated with aberrant trophoblast turnover and reduced activity of certain amino acid transporters, including the taurine transporter (TauT). Taurine is the most abundant amino acid in human placenta implying an important physiological role within this tissue. Unlike other amino acids, taurine is not incorporated into proteins and in non-placental cell types represents an important osmolyte involved in cell volume regulation, and is also cytoprotective. Here, we investigated the role of taurine in trophoblast turnover using RNA interference to deplete primary human trophoblast cells of TauT and reduce intracellular taurine content. Trophoblast differentiation was compromised in TauT-deficient cells, and susceptibility of these cells to an inflammatory cytokine that is elevated in FGR was increased, evidenced by elevated levels of apoptosis. These data suggest an important role for taurine in trophoblast turnover and cytoprotection. PMID:23519128

  9. Cortisol and IGF-1 synergistically up-regulate taurine transport by the rat skeletal muscle cell line, L6.

    PubMed

    Park, Sung-Hee; Lee, Haemi; Park, Taesun

    2004-01-01

    This study was undertaken to evaluate effects of exercise-induced hormones, cortisol, IGF-1, and beta-endorphin, on the regulation of taurine transport activity in rat skeletal myoblasts, L6 cells. Challenge of L6 cells with cortisol (100 nM) for 24 hrs resulted in a 165% increase in taurine transport activity, 220% increase in Vmax of the taurine transporter, and 55% increase in taurine transporter/ beta-actin mRNA level compared with untreated control cells. Neither IGF-1 (1 approximately 100 nM) nor beta-endorphin (1 approximately 20 nM), added in the incubation medium separately for 24 hrs, affected taurine uptake by L6 cells. However, when cells were co-treated with IGF-1 (10 nM) plus cortisol (100 nM), taurine transport activity (37% increase, p < 0.05), Vmax of the transporter (54%, p < 0.05), and taurine transporter/ beta-actin mRNA level were further increased compared to the value for cells treated with cortisol alone. These results suggest that taurine transport by skeletal muscle cells appear to be synergistically up-regulated during a prolonged exercise via elevated levels of cortisol and IGF-1 in muscle.

  10. Effect of mercury on taurine transport by the red blood cells of the marine polychaete, Glycera dibranchiata

    SciTech Connect

    Chen, C.W.; Preston, R.L.

    1987-08-01

    The objective of this study was to characterize the effects of heavy metal exposure on the transport of the amino acid, /sup 14/C-taurine, by the hemoglobin containing coelomocytes (red blood cells) of the marine polychaete, Glycera dibranchiata. Glycera has been used previously in studies on heavy metal absorption. Glycera red cells (RBCs) were used for this study because they contain a high concentration of taurine (190 mM) which has been implicated as a major osmolyte in cellular volume regulation in marine invertebrates. Taurine also appears to participate in osmoregulation of mammalian heart and brain tissue. The coelomic fluid bathing Glycera RBCs typically contains taurine at considerably lower concentrations (0.2 mM). The standing gradients (intracellular conc./extracellular conc.) for amino acids ranges from 40:1 for lysine to 950:1 for taurine. Preliminary experiments demonstrated that the maintenance of the large standing gradient for taurine was apparently due to the presence of a specific Na and Cl dependent taurine transport system in these cells. The fact that Glycera RBCs actively maintain large taurine gradients suggests that this tissue should be an excellent one to use in analysis of the mechanisms of heavy metal interaction with taurine transport systems.

  11. High expression of the taurine transporter TauT in primary cilia of NIH3T3 fibroblasts.

    PubMed

    Christensen, Søren T; Voss, Jesper W; Teilmann, Stefan C; Lambert, Ian H

    2005-05-01

    Taurine, present in high concentrations in various mammalian cells, is essential for regulation of cell volume, cellular oxidative status as well as the cellular Ca2+ homeostasis. Cellular taurine content is a balance between active uptake through the saturable, Na(+)-dependent taurine transporter TauT, and passive release via a volume-sensitive leak pathway. Here we demonstrate that: (i) TauT localizes to the primary cilium of growth-arrested NIH3T3 fibroblasts, (ii) long-term exposure to TNF(alpha) or hypertonic sucrose medium, i.e., growth medium supplemented with 100 mM sucrose, increases ciliary TauT expression and (iii) long-term exposure to hypertonic taurine medium, i.e., growth medium supplemented with 100 mM taurine, reduces ciliary TauT expression. These results point to an important role of taurine in the regulation of physiological processes located to the primary cilium.

  12. Altered hepatic sulfur metabolism in cystathionine β-synthase-deficient homocystinuria: regulatory role of taurine on competing cysteine oxidation pathways

    PubMed Central

    Jiang, Hua; Stabler, Sally P.; Allen, Robert H.; Abman, Steven H.; Maclean, Kenneth N.

    2014-01-01

    Cystathionine β-synthase-deficient homocystinuria (HCU) is a serious life-threatening inborn error of sulfur metabolism with poorly understood pathogenic mechanisms. We investigated the effect of HCU on hepatic cysteine oxidation in a transgenic mouse model of the disease. Cysteine dioxygenase (CDO) protein levels were 90% repressed without any change in mRNA levels. Cysteinesulfinic acid decarboxylase (CSAD) was induced at both the mRNA (8-fold) and protein (15-fold) levels. Cysteine supplementation normalized CDO protein levels without reversing the induction of CSAD. Regulatory changes in CDO and CSAD expression were proportional to homocysteine elevation, indicating a possible threshold effect. Hepatic and blood taurine levels in HCU animals were decreased by 21 and 35%, respectively, and normalized by cysteine supplementation. Expression of the cytoplasmic (GOT1) and mitochondrial (GOT2) isoforms of glutamic-oxaloacetic transaminase were repressed in HCU animals by 86 and 30%, respectively. HCU induced regulatory changes in CSAD, CDO, and GOT1 expression were normalized by taurine supplementation, indicating that cysteine is not the only sulfur compound that regulates hepatic cysteine oxidation. Collectively, our results indicate that HCU induces significant alterations of sulfur metabolism with the potential to contribute to pathogenesis and that cysteine and taurine have the potential to serve as adjunctive treatments in this disease.—Jiang, H., Stabler, S. P., Allen, R. H., Abman, S. H., Maclean, K. N. Altered hepatic sulfur metabolism in cystathionine β-synthase-deficient homocystinuria: regulatory role of taurine on competing cysteine oxidation pathways. PMID:24891521

  13. Component characteristics of the vectorial transport system for taurine in isolated bovine retinal pigment epithelium.

    PubMed Central

    Kundaiker, S; Hussain, A A; Marshall, J

    1996-01-01

    1. A wide range of substrate concentrations (5-1600 microM) were used to screen for the presence of systems capable of transporting taurine into isolated and free-floating samples of bovine retinal pigment epithelium (RPE). Both high and low affinity systems displaying Michaelis-Menten saturation kinetics were identified. The high affinity system was characterized by a K(m) of 23 microM and a V(max) of 86.7 pmol (5 min)(-1) (4 mm disc of tissue sample)(-1). Similarly, the low affinity system was characterized by a K(m) of 507 microM and a V(max) of 344 pmol (5 min)(-1)(4 mm disc)(-1). 2. Ussing-type incubation chambers and double-label radiotracer techniques were used to assess the presence of specific taurine carriers on apical and basolateral surfaces of the RPE. High affinity carriers were shown to be present on both surfaces and the kinetic constants (K(m) and V(max)) for apical and basolateral systems were determined as 23.2 microM and 34.8 pmol (5 min)(-1) (4 mm disc)(-1) and 29 microM and 54.7 pmol (5 min)(-1)(4 mm disc)(-1), respectively. Both these high affinity systems were sodium dependent with a Hill coefficient of about 2.0 indicating that two sodium ions are required for the translocation of one molecule of taurine. The low affinity system was unevenly distributed over the two surfaces of the RPE, basolateral capacities being roughly twofold higher. The basolateral system was totally insensitive to sodium whereas the apical one with 50% sodium sensitivity suggested the presence of low affinity carrier heterogeneity. 3. A temperature-dependent mechanism for the release of pre-loaded taurine from bovine RPF was also demonstrated. 4. The effect of [K+]o trans-RPF gradients on the vectorial transport of taurine across the isolated preparation was also investigated. The results demonstrated that the direction and magnitude of taurine transport could be controlled by physiological variations in the extracellular concentration of potassium. 5. The determined

  14. Altered hepatic sulfur metabolism in cystathionine β-synthase-deficient homocystinuria: regulatory role of taurine on competing cysteine oxidation pathways.

    PubMed

    Jiang, Hua; Stabler, Sally P; Allen, Robert H; Abman, Steven H; Maclean, Kenneth N

    2014-09-01

    Cystathionine β-synthase-deficient homocystinuria (HCU) is a serious life-threatening inborn error of sulfur metabolism with poorly understood pathogenic mechanisms. We investigated the effect of HCU on hepatic cysteine oxidation in a transgenic mouse model of the disease. Cysteine dioxygenase (CDO) protein levels were 90% repressed without any change in mRNA levels. Cysteinesulfinic acid decarboxylase (CSAD) was induced at both the mRNA (8-fold) and protein (15-fold) levels. Cysteine supplementation normalized CDO protein levels without reversing the induction of CSAD. Regulatory changes in CDO and CSAD expression were proportional to homocysteine elevation, indicating a possible threshold effect. Hepatic and blood taurine levels in HCU animals were decreased by 21 and 35%, respectively, and normalized by cysteine supplementation. Expression of the cytoplasmic (GOT1) and mitochondrial (GOT2) isoforms of glutamic-oxaloacetic transaminase were repressed in HCU animals by 86 and 30%, respectively. HCU induced regulatory changes in CSAD, CDO, and GOT1 expression were normalized by taurine supplementation, indicating that cysteine is not the only sulfur compound that regulates hepatic cysteine oxidation. Collectively, our results indicate that HCU induces significant alterations of sulfur metabolism with the potential to contribute to pathogenesis and that cysteine and taurine have the potential to serve as adjunctive treatments in this disease. © FASEB.

  15. The role of taurine in infant nutrition.

    PubMed

    Chesney, R W; Helms, R A; Christensen, M; Budreau, A M; Han, X; Sturman, J A

    1998-01-01

    The importance of taurine in the diet of pre-term and term infants has not always been clearly understood and is a topic of interest to students of infant nutrition. Recent evidence indicates that it should be considered one of the "conditionally essential" amino acids in infant nutrition. Plasma values for taurine will fall if infants are fed a taurine-free formula or do not have taurine provided in the TPN solution. Urine taurine values also fall, which is indicative of an attempt by the kidney to conserve taurine. The very-low-birth-weight infant, for a variety of reasons involving the maturation of tubular transport function, cannot maximally conserve taurine by enhancing renal reabsorption and, hence, is potentially at greater risk for taurine depletion than larger pre-term or term infants, and certainly more than older children who have taurine in their diet. Taurine has an important role in fat absorption in pre-term and possibly term infants and in children with cystic fibrosis. Because taurine-conjugated bile acids are better emulsifiers of fat than glycine-conjugated bile acids, the dietary (or TPN) intake has a direct influence on absorption of lipids. Taurine supplementation of formulas or TPN solutions could potentially serve to minimize the brain phospholipid fatty acid composition differences between formula-fed and human milk-fed infants. Taurine appears to have a role in infants, children, and even adults receiving most (> 75%) of their calories from TPN solutions in the prevention of granulation of the retina and electroencephalographic changes. Taurine has also been reported to improve maturation of auditory-evoked responses in pre-term infants, although this point is not fully established. Clearly, taurine is an important osmolyte in the brain and the renal medulla. At these locations, it is a primary factor in the cell volume regulatory process, in which brain or renal cells swell or shrink in response to osmolar changes, but return to their

  16. Taurine Attenuates Hepatic Inflammation in Chronic Alcohol-Fed Rats Through Inhibition of TLR4/MyD88 Signaling.

    PubMed

    Lin, Chao-Jen; Chiu, Chun-Ching; Chen, Yi-Chen; Chen, Mu-Lin; Hsu, Tsai-Ching; Tzang, Bor-Show

    2015-12-01

    Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1β were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling.

  17. Taurine Attenuates Hepatic Inflammation in Chronic Alcohol-Fed Rats Through Inhibition of TLR4/MyD88 Signaling

    PubMed Central

    Lin, Chao-Jen; Chiu, Chun-Ching; Chen, Yi-Chen; Chen, Mu-Lin

    2015-01-01

    Abstract Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1β were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling. PMID:26090712

  18. Transcriptomic and proteomic analysis of human hepatic stellate cells treated with natural taurine.

    PubMed

    Liang, Jian; Deng, Xin; Wu, Fa-Sheng; Tang, Yan-Fang

    2013-05-01

    The aim of this study was to investigate the differential expression of genes and proteins between natural taurine (NTau)‑treated hepatic stellate cells (HSCs) and control cells as well as the underlying mechanism of NTau in inhibiting hepatic fibrosis. A microculture tetrazolium (MTT) assay was used to analyze the proliferation of NTau‑treated HSCs. Flow cytometry was performed to compare the apoptosis rate between NTau-treated and non‑treated HSCs. Proteomic analysis using a combination of 2-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) was conducted to identify the differentially expressed proteins. Microarray analysis was performed to investigate the differential expression of genes and real-time polymerase chain reaction (PCR) was used to validate the results. The experimental findings obtained demonstrated that NTau decreased HSC proliferation, resulting in an increased number of cells in the G0/G1 phase and a reduced number of cells in the S phase. Flow cytometric analysis showed that NTau-treated HSCs had a significantly increased rate of apoptosis when compared with the non‑treated control group. A total of 15 differentially expressed proteins and 658 differentially expressed genes were identified by 2DE and MS, and microarray analysis, respectively. Gene ontology (GO) functional analysis indicated that these genes and proteins were enriched in the function clusters and pathways related to cell proliferation, cellular apoptosis and oxidation. The transcriptome and proteome analyses of NTau-treated HSCs demonstrated that NTau is able to significantly inhibit cell proliferation and promote cell apoptosis, highlighting its potential therapeutic benefits in the treatment of hepatic fibrosis.

  19. Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells.

    PubMed

    Tomi, Masatoshi; Tajima, Ayumi; Tachikawa, Masanori; Hosoya, Ken-ichi

    2008-10-01

    The purpose of this study was to identify the uptake mechanism of gamma-aminobutyric acid (GABA) via taurine transporter (Slc6a6/TauT) and its relationship with GABA transport at the inner BRB. Rat Slc6a6/TauT-transfected HeLa cells exhibited Na(+)-, Cl(-)-, and concentration-dependent [3H]GABA uptake with a Km of 1.5 mM. Taurine, beta-alanine, and GABA markedly inhibited Slc6a6/TauT-mediated uptake of [3H]GABA. The uptake of [3H]GABA by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) was Na(+)-, Cl(-)-, and concentration-dependent with a Km of 2.0 mM. This process was more potently inhibited by substrates of Slc6a6/TauT, taurine and beta-alanine, than those of GABA transporters, GABA and betaine. In the presence of taurine, there was competitive inhibition with a Ki of 74 microM. [3H]Taurine also exhibited competitive inhibition with a Ki of 1.8 mM in the presence of GABA. In conclusion, rat Slc6a6/TauT has the ability to use GABA as a substrate and Slc6a6/TauT-mediated GABA transport appears to be present at the inner BRB.

  20. Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia.

    PubMed

    Jamshidzadeh, Akram; Heidari, Reza; Abasvali, Mozhgan; Zarei, Mehdi; Ommati, Mohammad Mehdi; Abdoli, Narges; Khodaei, Forouzan; Yeganeh, Yasaman; Jafari, Faezeh; Zarei, Azita; Latifpour, Zahra; Mardani, Elnaz; Azarpira, Negar; Asadi, Behnam; Najibi, Asma

    2017-02-01

    Ammonia-induced mitochondrial dysfunction and energy crisis is known as a critical consequence of hepatic encephalopathy (HE). Hence, mitochondria are potential targets of therapy in HE. The current investigation was designed to evaluate the role of taurine treatment on the brain and liver mitochondrial function in a rat model of hepatic encephalopathy and hyperammonemia. The animals received thioacetamide (400mg/kg, i.p, for three consecutive days at 24-h intervals) as a model of acute liver failure and hyperammonemia. Several biochemical parameters were investigated in the serum, while the animals' cognitive function and locomotor activity were monitored. Mitochondria was isolated from the rats' brain and liver and several indices were assessed in isolated mitochondria. Liver failure led to cognitive dysfunction and impairment in locomotor activity in the rats. Plasma and brain ammonia was high and serum markers of liver injury were drastically elevated in the thioacetamide-treated group. An assessment of brain and liver mitochondrial function in the thioacetamide-treated animals revealed an inhibition of succinate dehydrogenase activity (SDA), collapsed mitochondrial membrane potential, mitochondrial swelling, and increased reactive oxygen species (ROS). Furthermore, a significant decrease in mitochondrial ATP was detected in the brain and liver mitochondria isolated from thioacetamide-treated animals. Taurine treatment (250, 500, and 1000mg/kg) decreased mitochondrial swelling, ROS, and LPO. Moreover, the administration of this amino acid restored brain and liver mitochondrial ATP. These data suggest taurine to be a potential protective agent with therapeutic capability against hepatic encephalopathy and hyperammonemia-induced mitochondrial dysfunction and energy crisis.

  1. Taurine and platelet aggregation

    SciTech Connect

    Nauss-Karol, C.; VanderWende, C.; Gaut, Z.N.

    1986-03-01

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 ..mu..M/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na/sup +/ and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with /sup 14/C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 ..mu..M, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet.

  2. Effect of taurine supplementation on hepatic metabolism and alleviation of cadmium toxicity and bioaccumulation in a marine teleost, red sea bream, Pagrus major.

    PubMed

    Hano, Takeshi; Ito, Katsutoshi; Kono, Kumiko; Ito, Mana; Ohkubo, Nobuyuki; Mochida, Kazuhiko

    2017-02-01

    This study was performed to unravel the mechanism of the beneficial action of taurine on marine teleost fish, red sea bream (Pagrus major), by analyzing the hepatic metabolism. Moreover, the ameliorative effects of the nutrient against cadmium toxicity and bioaccumulation were further evaluated. The fish were fed a diet containing 0 % (TAU0 %), 0.5 % (TAU0.5 %), or 5.0 % (TAU5.0 %) taurine for 40-55 days (d) and subjected to cadmium acute toxicity and bioaccumulation tests. Taurine deficiency in feed severely affected growth and the hepatic metabolic profiles of the fish, including a remarkable increase in myo-inositol, aspartate, and ß-alanine in the TAU0 % group, which indicates a complementary physiological response to taurine deficiency. For the acute toxicity test, fish were fed the test diets for 55 d and were then exposed to different dose of cadmium ranging from 0 to 5.6 mg/L for 96 h. Fish fed taurine had a higher tolerance to cadmium than those not fed taurine. For the bioaccumulation test, fish were fed the test diets for 40 d and then were chronically exposed to 0.2 mg/L of cadmium for 28 d followed by depuration for 21 d. Cadmium concentrations in the liver and muscle of fish fed TAU5.0 % were significantly lower than those of fish fed TAU0 % for the first 7 d of exposure and the first 7 d of elimination. Our findings suggest a possible mechanism for the beneficial role played by taurine and that the inclusion of taurine in fish aquaculture feed may reduce cadmium contamination of fish intended for human consumption.

  3. Downregulation of the taurine transporter TauT during hypo-osmotic stress in NIH3T3 mouse fibroblasts.

    PubMed

    Hansen, Daniel Bloch; Friis, Martin Barfred; Hoffmann, Else Kay; Lambert, Ian Henry

    2012-02-01

    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. © The Author(s) 2012. This article is published with open access at Springerlink.com

  4. Antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in rats fed a high fat diet.

    PubMed

    Du, Huan; Zhao, Xu; You, Jeong-Soon; Park, Ji-Yeon; Kim, Sung-Hoon; Chang, Kyung-Ja

    2010-08-24

    Nelumbo nucifera, known as sacred lotus, is a well-known medicinal plant and this lotus root is commonly used as food compared to different parts of this plant. This study was conducted to investigate the antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in high fat diet-induced obese rats. Thirty-two male Sprague-Dawley rats (4-week-old) were randomly divided into four groups (n=8) for 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus root hot water extract, HFR group; high fat diet + lotus root hot water extract + taurine, HFRT group). Lotus root hot water extract was orally administrated (400 mg/kg/day) to HFR and HFRT groups and the same amount of distilled water was orally administered to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). The activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum were lower in HFR and HFRT groups compared to HF group. Thiobarbituric acid reactive substance contents in all groups fed a high fat diet were higher compared to N group. The activities of hepatic antioxidant enzymes were higher in HFR and HFRT groups compared to HF group. These results suggest that lotus root hot water extract with taurine supplementation shows antioxidant and hepatic protective effects in high fat diet-induced obese rats.

  5. Mapping of the taurine transporter gene to mouse chromosome 6 and to the short arm of human chromosome 3

    SciTech Connect

    Patel, A.; Uhl, G.R.; Gregor, P.

    1995-01-01

    Transport proteins have essential functions in the uptake of neurotransmitters and neuromodulators. We have mapped the gene encoding the taurine transporter, Taut, to the central region of mouse chromosome 6. Analysis of a cross segregating the neurological mutant mnd2 excluded Taut as a candidate gene for this closely linked mutation. To map the human taurine transporter gene, TAUT, a sequence-tagged site (STS) corresponding to the 3{prime} untranslated region of the human cDNA was developed. TAUT was assigned to human chromosome 3 by typing this STS on a panel of somatic cell hybrids. Further analysis of a hybrid panel containing defined deletions of chromosome 3 suggested that TAUT maps to 3p21-p25. These data extend a conserved linkage group on mouse chromosome 6 and human chromosome 3p. Deletion of TAUT might contribute to some phenotypic features of the 3p{sup -} syndrome. 32 refs., 3 figs.

  6. Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents*

    PubMed Central

    Zhou, Yun; Holmseth, Silvia; Guo, Caiying; Hassel, Bjørnar; Höfner, Georg; Huitfeldt, Henrik S.; Wanner, Klaus T.; Danbolt, Niels C.

    2012-01-01

    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 [3H]taurine. Furthermore, most of the uptake of [3H]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. PMID:22896705

  7. Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents.

    PubMed

    Zhou, Yun; Holmseth, Silvia; Guo, Caiying; Hassel, Bjørnar; Höfner, Georg; Huitfeldt, Henrik S; Wanner, Klaus T; Danbolt, Niels C

    2012-10-12

    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.

  8. Preventive effects of taurine on development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.

    PubMed

    Chang, Yuan-Yen; Chou, Chung-Hsi; Chiu, Chih-Hsien; Yang, Kuo-Tai; Lin, Yi-Ling; Weng, Wei-Lien; Chen, Yi-Chen

    2011-01-12

    Nonalcoholic fatty liver (NAFL) is also called hepatic steatosis and has become an emergent liver disease in developed and developing nations. This study was to exam the preventive effects of taurine (Tau) on the development of hepatic steatosis via a hamster model. Although hepatic steatosis of hamsters was induced by feeding a high-fat/cholesterol diet, drinking water containing 0.35 and 0.7% Tau improved (p < 0.05) the serum lipid profile. Meanwhile, the smaller (p < 0.05) liver sizes and lower (p < 0.05) hepatic lipids in high-fat/cholesterol dietary hamsters drinking Tau may be partially due to higher (p < 0.05) fecal cholesterol, triacylglycerol, and bile acid outputs. In the regulation of lipid homeostasis, drinking a Tau solution upregulated (p < 0.05) low-density lipoprotein receptor and CYP7A1 gene expressions in high-fat/cholesterol dietary hamsters, which result in increased fecal cholesterol and bile acid outputs. Drinking a Tau solution also upregulated (p < 0.05) peroxisome proliferator-activated receptor-α (PPAR-α) and uncoupling protein 2 (UPC2) gene expressions in high-fat/cholesterol dietary hamsters, thus increasing energy expenditure. Besides, Tau also enhanced (p < 0.05) liver antioxidant capacities (GSH, TEAC, SOD, and CAT) and decreased (p < 0.05) lipid peroxidation (MDA), which alleviated liver damage in the high-fat/cholesterol dietary hamsters. Therefore, Tau shows preventive effects on the development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.

  9. Protective Role of Taurine against Arsenic-Induced Mitochondria-Dependent Hepatic Apoptosis via the Inhibition of PKCδ-JNK Pathway

    PubMed Central

    Das, Joydeep; Ghosh, Jyotirmoy; Manna, Prasenjit; Sil, Parames C.

    2010-01-01

    Background Oxidative stress-mediated hepatotoxic effect of arsenic (As) is mainly due to the depletion of glutathione (GSH) in liver. Taurine, on the other hand, enhances intracellular production of GSH. Little is known about the mechanism of the beneficial role of taurine in As-induced hepatic pathophysiology. Therefore, in the present study we investigated its beneficial role in As-induced hepatic cell death via mitochondria-mediated pathway. Methodology/Principal Findings Rats were exposed to NaAsO2 (2 mg/kg body weight for 6 months) and the hepatic tissue was used for oxidative stress measurements. In addition, the pathophysiologic effect of NaAsO2 (10 µM) on hepatocytes was evaluated by determining cell viability, mitochondrial membrane potential and ROS generation. As caused mitochondrial injury by increased oxidative stress and reciprocal regulation of Bcl-2, Bcl-xL/Bad, Bax, Bim in association with increased level of Apaf-1, activation of caspase 9/3, cleavage of PARP protein and ultimately led to apoptotic cell death. In addition, As markedly increased JNK and p38 phosphorylation with minimal disturbance of ERK. Pre-exposure of hepatocytes to a JNK inhibitor SP600125 prevented As-induced caspase-3 activation, ROS production and loss in cell viability. Pre-exposure of hepatocytes to a p38 inhibitor SB2035, on the other hand, had practically no effect on these events. Besides, As activated PKCδ and pre-treatment of hepatocytes with its inhibitor, rottlerin, suppressed the activation of JNK indicating that PKCδ is involved in As-induced JNK activation and mitochondrial dependent apoptosis. Oral administration of taurine (50 mg/kg body weight for 2 weeks) both pre and post to NaAsO2 exposure or incubation of the hepatocytes with taurine (25 mM) were found to be effective in counteracting As-induced oxidative stress and apoptosis. Conclusions/Significance Results indicate that taurine treatment improved As-induced hepatic damages by inhibiting PKC

  10. Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCdelta-JNK pathway.

    PubMed

    Das, Joydeep; Ghosh, Jyotirmoy; Manna, Prasenjit; Sil, Parames C

    2010-09-07

    Oxidative stress-mediated hepatotoxic effect of arsenic (As) is mainly due to the depletion of glutathione (GSH) in liver. Taurine, on the other hand, enhances intracellular production of GSH. Little is known about the mechanism of the beneficial role of taurine in As-induced hepatic pathophysiology. Therefore, in the present study we investigated its beneficial role in As-induced hepatic cell death via mitochondria-mediated pathway. Rats were exposed to NaAsO(2) (2 mg/kg body weight for 6 months) and the hepatic tissue was used for oxidative stress measurements. In addition, the pathophysiologic effect of NaAsO(2) (10 microM) on hepatocytes was evaluated by determining cell viability, mitochondrial membrane potential and ROS generation. As caused mitochondrial injury by increased oxidative stress and reciprocal regulation of Bcl-2, Bcl-xL/Bad, Bax, Bim in association with increased level of Apaf-1, activation of caspase 9/3, cleavage of PARP protein and ultimately led to apoptotic cell death. In addition, As markedly increased JNK and p38 phosphorylation with minimal disturbance of ERK. Pre-exposure of hepatocytes to a JNK inhibitor SP600125 prevented As-induced caspase-3 activation, ROS production and loss in cell viability. Pre-exposure of hepatocytes to a p38 inhibitor SB2035, on the other hand, had practically no effect on these events. Besides, As activated PKCdelta and pre-treatment of hepatocytes with its inhibitor, rottlerin, suppressed the activation of JNK indicating that PKCdelta is involved in As-induced JNK activation and mitochondrial dependent apoptosis. Oral administration of taurine (50 mg/kg body weight for 2 weeks) both pre and post to NaAsO(2) exposure or incubation of the hepatocytes with taurine (25 mM) were found to be effective in counteracting As-induced oxidative stress and apoptosis. Results indicate that taurine treatment improved As-induced hepatic damages by inhibiting PKCdelta-JNK signalling pathways. Therefore taurine

  11. Identification and functional characterization of a dual GABA/taurine transporter in the bullfrog retinal pigment epithelium

    PubMed Central

    1995-01-01

    Intracellular microelectrodes, fluorescence imaging, and radiotracer flux techniques were used to investigate the physiological response of the retinal pigment epithelium (RPE) to the major retinal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). GABA is released tonically in the dark by amphibian horizontal cells, but is not taken up by the nearby Muller cells. Addition of GABA to the apical bath produced voltage responses in the bullfrog RPE that were not blocked nor mimicked by any of the major GABA-receptor antagonists or agonists. Nipecotic acid, a substrate for GABA transport, inhibited the voltage effects of GABA. GABA and nipecotic acid also inhibited the voltage effects of taurine, suggesting that the previously characterized beta- alanine sensitive taurine carrier also takes up GABA. The voltage responses of GABA, taurine, nipecotic acid, and beta-alanine all showed first-order saturable kinetics with the following Km's: GABA (Km = 160 microM), beta-alanine (Km = 250 microM), nipecotic acid (Km = 420 microM), and taurine (Km = 850 microM). This low affinity GABA transporter is dependent on external Na, partially dependent on external Cl, and is stimulated in low [K]o, which approximates subretinal space [K]o during light onset. Apical GABA also produced a significant conductance increase at the basolateral membrane. These GABA-induced conductance changes were blocked by basal Ba2+, suggesting that GABA decreased basolateral membrane K conductance. In addition, the apical membrane Na/K ATPase was stimulated in the presence of GABA. A model for the interaction between the GABA transporter, the Na/K ATPase, and the basolateral membrane K conductance accounts for the electrical effects of GABA. Net apical-to-basal flux of [3H]-GABA was also observed in radioactive flux experiments. The present study shows that a high capacity GABA uptake mechanism with unique pharmacological properties is located at the RPE apical membrane and could play an

  12. Effects of the transport site conformation on the binding of external NAP-taurine to the human erythrocyte anion exchange system: evidence for intrinsic asymmetry

    SciTech Connect

    Knauf, P.A.; Law, F.Y.; Tarshis, T.; Furuya, W.

    1984-05-01

    External N-(4-azido (NAP-taurine) inhibits human red cell chloride exchange by binding to a site that is distinct from the chloride transport site. Increases in the intracellular chloride concentration (at constant external chloride) cause an increase in the inhibitory potency of external NAP-taurine. This effect is not due to the changes in pH or membrane potential that usually accompany a chloride gradient, since even when these changes are reversed or eliminated the inhibitory potency remains high. According to the ping-pong model for anion exchange, such transmembrane effects of intracellular chloride on external NAP-taurine can be explained if NAP-taurine only binds to its site when the transport site is in the outward-facing (E/sub o/ or ECl/sub o/) form. Since NAP-taurine prevents the conformational change from ECl/sub o/ to ECl/sub i/, it must lock the system in the outward-facing form. NAP-taurine can therefore be used just like the competitive inhibitor H/sub 2/DIDS (4,4'-diisothiocyano-1,2-diphenylethane-2,2'-disulfonic acid) to monitor the fraction of transport sites that face outward. A quantitative analysis of the effects of chloride gradients on the inhibitory potency of NAP-taurine and H/sub 2/DIDS reveals that the transport system is intrinsically asymmetric, such that when Cl/sub i/ = Cl/sub o/, most of the unloaded transport sites face the cytoplasmic side of the membrane. 30 references, 7 figures, 3 tables.

  13. Oxidative stress and dysregulation of the taurine transporter in high-glucose-exposed human Schwann cells: implications for pathogenesis of diabetic neuropathy

    PubMed Central

    Askwith, Trevor; Zeng, Wei; Eggo, Margaret C.; Stevens, Martin J.

    2009-01-01

    In human Schwann cells, the role of taurine in regulating glucose-induced changes in antioxidant defense systems has been examined. Treatment with high glucose for 7 days induced reactive oxygen species, increased 4-hydroxynoneal adducts (20 ± 5%, P < 0.05) and poly(ADP-ribosyl)ated proteins (40 ± 13%, P < 0.05). Increases in these markers of oxidative stress were reversed by simultaneous incubation in 0.25 mM taurine. Both high glucose and taurine independently increased superoxide dismutase and catalase activity and decreased glutathione levels, but their effects were not additive. Glucose reduced taurine transporter (TauT) mRNA and protein in a dose-dependent manner with maximal decreases of 66 ± 6 and 63 ± 12%, respectively (P < 0.05 both). The Vmax for taurine uptake was decreased in 30 mM glucose from 61 ± 5 to 42 ± 3 pmol·min−1·mg protein−1 (P < 0.001). Glucose-induced TauT downregulation could be reversed by inhibition of aldose reductase, a pathway that depletes NADPH and increases osmotic stress and protein glycation. TauT protein was increased more than threefold, and the Vmax for taurine uptake doubled (P < 0.05 both) by prooxidants. TauT downregulation was reversed both by treatment with the antioxidant α-lipoic acid, which increased TauT mRNA by 60% and Vmax by 50% (P < 0.05 both), and by the aldose reductase inhibitor sorbinil, which increased TauT mRNA 380% and Vmax by 98% (P < 0.01 both). These data highlight the potential therapeutic benefits of taurine supplementation in diabetic complications and provide mechanisms whereby taurine restoration could be achieved in order to prevent or reverse diabetic complications. PMID:19602579

  14. Physiological role of taurine--from organism to organelle.

    PubMed

    Lambert, I H; Kristensen, D M; Holm, J B; Mortensen, O H

    2015-01-01

    Taurine is often referred to as a semi-essential amino acid as newborn mammals have a limited ability to synthesize taurine and have to rely on dietary supply. Taurine is not thought to be incorporated into proteins as no aminoacyl tRNA synthetase has yet been identified and is not oxidized in mammalian cells. However, taurine contributes significantly to the cellular pool of organic osmolytes and has accordingly been acknowledged for its role in cell volume restoration following osmotic perturbation. This review describes taurine homeostasis in cells and organelles with emphasis on taurine biophysics/membrane dynamics, regulation of transport proteins involved in active taurine uptake and passive taurine release as well as physiological processes, for example, development, lung function, mitochondrial function, antioxidative defence and apoptosis which seem to be affected by a shift in the expression of the taurine transporters and/or the cellular taurine content. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  15. Taurine Homeostasis and Volume Control.

    PubMed

    Pasantes-Morales, Herminia

    2017-01-01

    Taurine content is high (mM) in mammalian brain. By its major role as an osmolyte, taurine contributes to the cell volume control, which is particularly critical in the brain. Taurine participates in osmotic adjustments required to maintain the organization and size of intracellular compartments. It counteracts volume fluctuations in unbalanced transmembrane fluxes of ions and neurotransmitters, preserving the functional synaptic contacts. Taurine has a key role in the long-term adaptation to chronic hyponatremia as well as in other pathologies leading to brain edema. Together with other osmolytes, taurine corrects cell shrinkage, preventing mysfunction of organelles and apoptosis. Swelling corrective taurine efflux occurs through a leak pathway, likely formed by LCRR8 protein isoforms. Shrinkage-activated influx comes largely by the increased activity of the Na(+)/Cl(-)-dependent transporter. The brain taurine pool results from the equilibrium between (i) dietary intake and active transport into the cell, (ii) synthesis in the brain itself or import of that synthesized elsewhere, and (iii) leak and posterior excretion. The interplay between these elements preserves brain taurine homeostasis in physiological conditions and permits the proper adjustments upon deviations of normal in the internal/external environment.

  16. Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat.

    PubMed

    Zouboulis-Vafiadis, I; Dumont, M; Erlinger, S

    1982-09-01

    It has been reported that biliary secretion is the limiting step in the hepatic transport of bile acids by the hepatocyte from plasma to canalicular bile. The aim of the present study was to examine the role of conjugation in the transport process using ursodeoxycholate (UDCA) and tauroursodeoxycholate (TUDCA), two bile acid with low liver toxicity. Rats were given constant intravenous infusions of cholate (C), taurocholate (TC), UDCA, or TUDCA at progressively increasing rates. The biliary maximum secretory rate (SRm), in nmol . min-1 . 100 g body wt-1, for TC (1,835.2 +/- 135.5, mean +/- SE) was not significantly different from that of C (1,749.4 +/- 85.6). In contrast, the SRm for TUDCA (5,909.4 +/- 304.4) was approximately sevenfold that of UDCA (802.1 +/- 134.2), the difference being statistically significant (P less than 0.001). The SRm of UDCA in the presence of a taurine infusion (1,367 +/- 84.4) was higher than that of UDCA infused alone but still much lower than that of TUDCA. Phenobarbital sodium pretreatment did not increase SRm of UDCA alone or in the presence of a taurine infusion. These results suggest that in the rat 1) conjugation is the rate-limiting step in the overall transport of UDCA (and perhaps other bile acids) by the liver, and 2) the conjugation process itself is limiting, rather than the availability of taurine. They support the view that, although not mandatory for secretion into bile, conjugation of bile acids confers a biological advantage, possibly by increasing the solubility of the bile acid.

  17. Cholestasis induced by total parenteral nutrition: effects of the addition of Taurine (Tauramin®) on hepatic function parameters; possible synergistic action of structured lipids (SMOFlipid®).

    PubMed

    González-Contreras, J; Villalobos Gámez, J L; Gómez-Sánchez, A I; García-Almeida, J M; Enguix Armanda, A; Rius Díaz, F; Lucena González, M I

    2012-01-01

    Assess the hepatoprotective effect of Taurine (Tau) in cases of hepatic cholestasis induced by Total Parenteral Nutrition (TPN). We describe a retrospective series of 54 patients who received TPN, in which cholestasis was detected at an (Intermediate) point that separates the duration of TPN into 2 Phases. From this moment -Phase 2- on, and according to clinical criteria, some patients (Group A, n = 27) received amino acids with Tau (22.41 ± 3.57 mg/kg/day)(Tauramin®), while the rest (Group B, n = 27) received the standard solution without Tau. The mean TPN durations were 39.2 ± 17.1 and 36.4 ± 18.1 days respectively, with the Intermediate points on days 19.56 ± 10.51 and 17.89 ± 11.14. They all received diets that were homogeneous in terms of kcal and macronutrients. In Phase 2, 21 patients from Group A received structured lipids (SMOFlipid®); while 20 from Group B received soy MCT/LCT [ Medium Chain Triglycerides/Long Chain Triglycerides ] (physical or structured mixture). In a retrospective study, differences could not be avoided. The analytical parameters from three periods (Initial, Intermediate, and Final) were obtained from Nutridata® and Servolab®. We compared interperiod values using the Wilcoxon test SPSS® (p < 0.05). After introducing Taurine AST, ALT, and GGT were significantly reduced; Bilirubin was also reduced, but not significantly. The values obtained for GGT in Group A were (Mean(σ)/median): Initial 48.6 (23.1)/46; Intermediate 473.7 (276.2)/438, and Final 328.9 (190.4)/305. We stress that the mean GGT value is reduced by 30.56% after adding Taurine, while in its absence all parameters are elevated, and mean GGT increases 45.36%. These results show Taurine's hepatoprotective effect and support its use in cases of TPN-induced cholestasis. We acknowledge the possibility that the differences between SMOF and the MCT/LCT mixtures also may have influenced the results in a combined effect with taurine.

  18. Comparison of serum and plasma taurine values in Bengal tigers with values in taurine-sufficient and -deficient domestic cats.

    PubMed

    Pickett, J P; Chesney, R W; Beehler, B; Moore, C P; Lippincott, S; Sturman, J; Ketring, K L

    1990-01-15

    A white Bengal tiger was determined to have a central retinal lesion and a central visual defect. Because of the known association between feline central retinal degeneration (CRD) and taurine deficiency in domestic cats, plasma concentrations of taurine were measured in this tiger. Serum concentrations of taurine, methionine, and cystine also were measured in white Bengal tigers, orange Bengal tigers, taurine-sufficient domestic cats, and taurine-deprived and tissue-taurine-depleted visually impaired cats with CRD. Hepatic and brain enzymes responsible for taurine synthesis were identified in tissue specimens from an orange Bengal tiger. Serum taurine concentrations were lower in white vs orange tigers, but were not as low as those in cats with CRD. Thus, we concluded that taurine depletion did not account for the central retinal lesion in the white Bengal tiger.

  19. Taurine Biosynthesis in a Fish Liver Cell Line (ZFL) Adapted to a Serum-Free Medium.

    PubMed

    Liu, Chieh-Lun; Watson, Aaron M; Place, Allen R; Jagus, Rosemary

    2017-05-25

    Although taurine has been shown to play multiple important physiological roles in teleosts, little is known about the molecular mechanisms underlying dietary requirements. Cell lines can provide useful tools for deciphering biosynthetic pathways and their regulation. However, culture media and sera contain variable taurine levels. To provide a useful cell line for the investigation of taurine homeostasis, an adult zebrafish liver cell line (ZFL) has been adapted to a taurine-free medium by gradual accommodation to a commercially available synthetic medium, UltraMEM™-ITES. Here we show that ZFL cells are able to synthesize taurine and be maintained in medium without taurine. This has allowed for the investigation of the effects of taurine supplementation on cell growth, cellular amino acid pools, as well as the expression of the taurine biosynthetic pathway and taurine transporter genes in a defined fish cell type. After taurine supplementation, cellular taurine levels increase but hypotaurine levels stay constant, suggesting little suppression of taurine biosynthesis. Cellular methionine levels do not change after taurine addition, consistent with maintenance of taurine biosynthesis. The addition of taurine to cells grown in taurine-free medium has little effect on transcript levels of the biosynthetic pathway genes for cysteine dioxygenase (CDO), cysteine sulfinate decarboxylase (CSAD), or cysteamine dioxygenase (ADO). In contrast, supplementation with taurine causes a 30% reduction in transcript levels of the taurine transporter, TauT. This experimental approach can be tailored for the development of cell lines from aquaculture species for the elucidation of their taurine biosynthetic capacity.

  20. Taurine and fish development: insights for the aquaculture industry.

    PubMed

    Pinto, Wilson; Rønnestad, Ivar; Dinis, Maria Teresa; Aragão, Cláudia

    2013-01-01

    Expansion of the aquaculture industry is limited by incomplete knowledge on fish larval nutritional requirements. Nevertheless, it is believed that dietary taurine deficiencies may be particularly critical for fish larvae. The reasons include the high taurine levels found during egg and yolk-sac stages of fish, suggesting that taurine may be of pivotal importance for larval development. Moreover, unlike aquaculture feeds, natural preys of fish larvae contain high taurine levels, and dietary taurine supplementation has been shown to increase larval growth in several fish species. This study aimed to further explore the physiological role of taurine during fish development. Firstly, the effect of dietary taurine supplementation was assessed on growth of gilthead sea bream (Sparus aurata) larvae and growth, metamorphosis success and amino acid metabolism of Senegalese sole (Solea senegalensis) larvae. Secondly, the expression of taurine transporter (TauT) was characterised by qPCR in sole larvae and juveniles. Results showed that dietary taurine supplementation did not increase sea bream growth. However, dietary taurine supplementation significantly increased sole larval growth, metamorphosis success and amino acid retention. Metamorphosis was also shown to be an important developmental trigger to promote taurine transport in sole tissues, while evidence for an enterohepatic recycling pathway for taurine was found in sole at least from juvenile stage. Taken together, our studies showed that the dependence of dietary taurine supplementation differs among fish species and that taurine has a vital role during the ontogenetic development of flatfish, an extremely valuable group targeted for aquaculture production.

  1. Interaction of GABA-mimetics with the taurine transporter (TauT, Slc6a6) in hyperosmotic treated Caco-2, LLC-PK1 and rat renal SKPT cells.

    PubMed

    Rasmussen, Rune Nørgaard; Lagunas, Candela; Plum, Jakob; Holm, René; Nielsen, Carsten Uhd

    2016-01-20

    The aim of the present study was to investigate if basic GABA-mimetics interact with the taurine transporter (TauT, Slc6a6), and to find a suitable cell based model that is robust towards extracellular changes in osmolality during uptake studies. Taurine uptake was measured in human Caco-2 cells, porcine LLC-PK1 cells, and rat SKPT cells using radiolabelled taurine. Hyperosmotic conditions were obtained by incubation with raffinose (final osmolality of 500mOsm) for 24h prior to the uptake experiments. Expression of the taurine transporter, TauT, was investigated at the mRNA level by real-time PCR. Uptake of the GABA-mimetics gaboxadol and vigabatrin was investigated in SKPT cells, and quantified by liquid scintillation or HPLC-MS/MS analysis, respectively. The uptake rate of [(3)H]-taurine was Na(+) and Cl(-) and concentration dependent with taurine with an apparent Vmax of 6.3±1.6pmolcm(-2)min(-1) and a Km of 24.9±15.0μM. β-alanine, nipecotic acid, gaboxadol, GABA, vigabatrin, δ-ALA and guvacine inhibited the taurine uptake rate in a concentration dependent manner. The order of affinity for TauT was β-alanine>GABA>nipecotic acid>guvacine>δ-ALA>vigabatrin>gaboxadol with IC50-values of 0.04, 1.07, 2.02, 4.19, 4.94, 31.4 and 39.9mM, respectively. In conclusion, GABA mimetics inhibited taurine uptake in hyperosmotic rat renal SKPT cells. SKPT cells, which seem to be a useful model for investigating taurine transport in the short-term presence of high concentrations of osmolytes. Furthermore, analogues of β-alanine appear to have higher affinities for TauT than GABA-analogues.

  2. Physiological roles of taurine in heart and muscle

    PubMed Central

    2010-01-01

    Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an

  3. Physiological roles of taurine in heart and muscle.

    PubMed

    Schaffer, Stephen W; Jong, Chian Ju; Ramila, K C; Azuma, Junichi

    2010-08-24

    Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an

  4. Taurine and tea polyphenols combination ameliorate nonalcoholic steatohepatitis in rats.

    PubMed

    Zhu, Wenhua; Chen, Siwen; Chen, Ronggui; Peng, Zhiqing; Wan, Jun; Wu, Benyan

    2017-09-08

    Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease, for which there is currently no safe and effective drug for therapy. In this study, we explored the effects of taurine, tea polyphenols (TPs), or a combination thereof, on NASH rats. Rats were divided into a normal group, a high-fat diet induced model group and a treatment group (including taurine, TPs, or taurine + TPs treatment for 8 weeks). Twelve weeks later, all rats were sacrificed, and serum transaminase, lipid and lipopolysaccharide levels and hepatic oxidative stress levels were determined. Histological changes were evaluated. In NASH rats, hepatocyte damage, lipid disturbance, oxidative stress and elevated lipopolysaccharide levels were confirmed. Taurine treatment alleviated hepatocyte damage and oxidative stress. TPs treatment improved lipid metabolism and increased hepatic antioxidant activity. The therapeutic effects of taurine + TPs treatment on hepatocyte damage, lipid disturbance, and oxidative stress were superior to those of taurine and TPs treatment, respectively. Taurine, TPs and their combination all decreased serum lipopolysaccharide levels in NASH rats, but the combination of the compounds caused these levels to decrease more significantly than taurine or TPs treatment alone. Taurine combined with TPs treatment could relieve NASH by alleviating hepatocyte damage, decreasing oxidative stress and improving lipid metabolism and gut flora disturbance partly. Taurine and TPs combination may act as a new effective medicine for treating NASH patients.

  5. Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys.

    PubMed

    van Stijn, Mireille F M; Vermeulen, Mechteld A R; Siroen, Michiel P C; Wong, Leanne N; van den Tol, M Petrousjka; Ligthart-Melis, Gerdien C; Houdijk, Alexander P J; van Leeuwen, Paul A M

    2012-07-01

    Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Taurine's effects on the neuroendocrine functions of pancreatic β cells.

    PubMed

    Cuttitta, Christina M; Guariglia, Sara R; Idrissi, Abdeslem El; L'amoreaux, William J

    2013-01-01

    Taurine plays significant physiological roles, including those involved in neurotransmission. Taurine is a potent γ-aminobutyric acid (GABA) agonist and alters cellular events via GABA(A) receptors. Alternately, taurine is transported into cells via the high affinity taurine transporter (TauT), where it may also play a regulatory role. We have previously demonstrated that treatment of Hit-T15 cells with 1 mM taurine for 24 h significantly decreases insulin and GABA levels. We have also demonstrated that chronic in vivo administration of taurine results in an up-regulation of glutamic acid decarboxylase (GAD), the key enzyme in GABA synthesis. Here, we wished to test if administration of 1 mM taurine for 24 h may increase release of another β cell neurotransmitter somatostatin (SST) and also directly impact up-regulation of GAD synthesis. Treatment with taurine did not significantly alter levels of SST (p > 0.05) or GAD67 (p > 0.05). This suggests that taurine does not directly affect SST release, nor does it directly affect GAD synthesis. Taken together with our observation that taurine does promote GABA release via large dense-core vesicles, the data suggest that taurine may alter membrane potential, which in turn would affect calcium flux. We show here that 1 mM taurine does not alter intracellular Ca(2+) concentrations from 20 to 80 s post treatment (p > 0.05), but does increase Ca(2+) flux between 80 and 200 s post-treatment (p < 0.005). This suggests that taurine may induce a biphasic response in β cells. The initial response of taurine via GABA(A) receptors hyperpolarizes β cell and sequesters Ca(2+). Subsequently, taurine may affect Ca(2+) flux in long term via interaction with K(ATP) channels.

  7. The role of taurine on skeletal muscle cell differentiation.

    PubMed

    Miyazaki, Teruo; Honda, Akira; Ikegami, Tadashi; Matsuzaki, Yasushi

    2013-01-01

    Taurine abundantly contained in the skeletal muscle has been considered as one of essential factors for the differentiation and growth of skeletal muscles. The previous studies in the taurine transporter knockout mice showed that deficiency of taurine content in the skeletal muscle caused incomplete muscular developments, morphological abnormalities, and exercise abilities. In fetal and neonatal periods, taurine must be an essential amino acid due to no biosynthesis capacity, and therefore, taurine should be endogenously supplied through placenta and maternal milk. In general cell culture condition, taurine contained in the culture medium is absent or few, and therefore, most of cultured cells are in taurine-deficient condition. In the present study, we confirmed, in cultured mouse differentiable myoblast, taurine treatment significantly enhanced the differentiation to myotube in a dose-dependent manner, while these effects were abrogated by inhibitions of taurine transport and Ca(2+) signaling pathway.The present study suggested that exogenous taurine might play a key role on the mature differentiation/growth of the skeletal muscle during development period through Ca(2+) signaling pathway, and therefore, taurine would contribute the muscle recovery after damages.

  8. Role of Hepatic Drug Transporters in Drug Development.

    PubMed

    Liu, Houfu; Sahi, Jasminder

    2016-07-01

    Hepatic drug transporters can play an important role in pharmacokinetics and the disposition of therapeutic drugs and endogenous substances. Altered function of hepatic drug transporters due to drug-drug interactions (DDIs), genetic polymorphisms, and disease states can often result in a change in systemic and/or tissue exposure and subsequent pharmacological/toxicological effects of their substrates. Regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japan Pharmaceuticals and Medical Devices Agency have issued guidance for industry on drug interaction studies, which contain comprehensive recommendations on in vitro and in vivo study tools and cutoff values to evaluate the DDI potential of new molecular entities mediated by hepatic drug transporters. In this report we summarize the latest regulatory and scientific progress of hepatic drug transporters in clinical DDIs, pharmacogenetics, drug-induced liver injury (DILI), as well as methods for predicting transporter-mediated pharmacokinetics and DDIs. © 2016, The American College of Clinical Pharmacology.

  9. Imidazole-4-acetic acid, a new lead structure for interaction with the taurine transporter in outer blood-retinal barrier cells.

    PubMed

    Valembois, Sophie; Krall, Jacob; Frølund, Bente; Steffansen, Bente

    2017-03-01

    Retinal diseases leading to impaired vision and ultimately blindness are mainly characterized by ischemic and hypoxic stress. Targeting the retinal ρ-containing γ-aminobutyric acid type A receptors (ρ GABAARs) and thereby decreasing the retinal neuronal activity has been proposed as a novel therapeutic approach. The taurine transporter (TAUT) plays a key role in the retinal transport of GABA and has been previously suggested to display a higher functional activity in the retina compared to the brain. TAUT would therefore stand as a suitable target for the selective delivery of ρ GABAAR ligands into the retina. Consequently, an in vitro model of TAUT at the outer blood-retinal barrier (BRB) was developed and characterized using the ARPE-19 cell line. Furthermore, the structural requirements of GABAAR ligands for interacting with TAUT at the BRB were investigated for a series of standard GABAAR ligands by testing their ability to inhibit the TAUT-mediated influx of taurine in ARPE-19 cells. Results showed that taurine influx was seven-fold higher when the ARPE-19 cells were cultured under hyperosmotic conditions and was demonstrated to display saturable kinetics (Km=27.7±2.2μM and Jmax=24.2±0.6pmol/cm(2)·min). Furthermore, the taurine influx was significantly inhibited in a concentration-dependent manner by GABA and imidazole-4-acetic acid (IAA), which is a naturally occurring metabolite of histamine. These compounds display similar Ki values of 644.2μM and 658.6μM, respectively. Moreover, IAA demonstrated higher inhibitory properties than the other tested GABA analogs: 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), 4,5,6,7-tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP), muscimol, and thiomuscimol. These studies demonstrated that IAA interacts with TAUT, which makes IAA a new lead structure in the development of new compounds, which are not only interacting with TAUT but also potent ρ GABAAR ligands.

  10. Effects of zinc ex vivo on taurine uptake in goldfish retinal cells

    PubMed Central

    2010-01-01

    Background Taurine and zinc exert neurotrophic effects in the central nervous system. Current studies demonstrate that Na+/Cl- dependent neurotransmitter transporters, similar to that of taurine, are modulated by micromolar concentrations of zinc. This study examined the effect of zinc sulfate ex vivo on [3H]taurine transport in goldfish retina. Methods Isolated cells were incubated in Ringer with zinc (0.1–100 µM). Taurine transport was done with 50 nM [3H]taurine or by isotopic dilution with taurine (0.001–1 mM) and 50 nM [3H]taurine. Results Zinc reduced the capacity of taurine transport without changes in affinity, and caused a noncompetitive inhibition of high affinity taurine transport, with an EC50= 0.072 µM. The mechanism by which zinc affects taurine transport is unknown at the present. Conclusions There may be a binding site of zinc in the transporter that affects union or translocation of taurine, or possibly the formation of taurine-zinc complexes, rather than free zinc, could affect the operation of the transporter. PMID:20804587

  11. Role of hepatic transporters in prevention of bile acid toxicity after partial hepatectomy in mice

    PubMed Central

    Csanaky, Iván L.; Aleksunes, Lauren M.; Tanaka, Yuji; Klaassen, Curtis D.

    2009-01-01

    The enterohepatic recirculation of bile acids (BAs) is important in several physiological processes. Although there has been considerable research on liver regeneration after two-thirds partial hepatectomy (PHx), little is known about how the liver protects itself against BA toxicity during regeneration. In this study, various BAs in plasma and liver, the composition of micelle-forming bile constituents, as well as gene expression of the main hepatobiliary transporters were quantified in sham-operated and PHx mice 24 and 48 h after surgery. PHx did not influence the hepatic concentrations of taurine-conjugated BAs (T-BA) but increased the concentration of glycine-conjugated (G-BA) and unconjugated BAs. Total BA excretion (μg·min−1·g liver wt−1) increased 2.4-fold and was accompanied by a 55% increase in bile flow after PHx. The plasma concentrations of T-BAs (402-fold), G-BAs (17-fold), and unconjugated BAs (500-fold) increased. The mRNA and protein levels of the BA uptake transporter Ntcp were unchanged after PHx, whereas the canalicular Bsep protein increased twofold at 48 h. The basolateral efflux transporter Mrp3 was induced at the mRNA (2.6-fold) and protein (3.1-fold) levels after PHx, which may contribute to elevated plasma BA and bilirubin levels. Biliary phospholipid excretion was nearly doubled in PHx mice, most likely owing to increased mRNA expression of the phospholipid transporter, Mdr2. In conclusion, the remnant liver after PHx excretes 2.5-fold more BAs and three times more phospholipids per gram liver than the sham-operated mouse liver. Upregulation of phospholipid transport may be important in protecting the biliary tract from BA toxicity during PHx. PMID:19497955

  12. Taurine and atherosclerosis.

    PubMed

    Murakami, Shigeru

    2014-01-01

    Taurine is abundantly present in most mammalian tissues and plays a role in many important physiological functions. Atherosclerosis is the underlying mechanism of cardiovascular disease including myocardial infarctions, strokes and peripheral artery disease and remains a major cause of morbidity and mortality worldwide. Studies conducted in laboratory animal models using both genetic and dietary models of hyperlipidemia have demonstrated that taurine supplementation retards the initiation and progression of atherosclerosis. Epidemiological studies have also suggested that taurine exerts preventive effects on cardiovascular diseases. The present review focuses on the effects of taurine on the pathogenesis of atherosclerosis. In addition, the potential mechanisms by which taurine suppress the development of atherosclerosis will be discussed.

  13. A Novel Cysteine Sulfinic Acid Decarboxylase Knock-Out Mouse: Taurine Distribution in Various Tissues With and Without Taurine Supplementation.

    PubMed

    Park, Eunkyue; Park, Seung Yong; Cho, In Soo; Kim, Bo Sook; Schuller-Levis, Georgia

    2017-01-01

    Taurine, a sulfur containing amino acid, has various physiological functions including development of the eye and brain, immune function, reproduction, osmo-regulatory function as well as anti-oxidant and anti-inflammatory activities. In order to understand the physiological role, we developed taurine deficient mice deleting a rate-liming enzyme, cysteine sulfinic acid decarboxylase (CSAD) for biosynthesis of taurine. Taurine was measured in various tissues including the liver, brain, lung, spleen, thymus, pancreas, heart, muscle and kidney as well as plasma from CSAD knock-out mice (CSAD KO) with and without treatment of taurine in the drinking water at the age of 2 months (2 M). Taurine was determined using HPLC as a phenylisothiocyanate derivative of taurine at 254 nm. Taurine concentrations in the liver and kidney from homozygotes of CSAD KO (HO), in which CSAD level is high, were 90% and 70% lower than WT, respectively. Taurine concentrations in the brain, spleen and lung, where CSAD level is low, were 21%, 20% and 28% lower than WT, respectively. At 2 M, 1% taurine treatment of HO restored taurine concentrations in all tissues compared to that of WT. To select an appropriate taurine treatment, HO were treated with various concentrations (0.05, 0.2, 1%) of taurine for 4 months (4 M). Restoration of taurine in all tissues except the liver, kidney and lung requires 0.05% taurine to be restored to that of WT. The liver and kidney restore taurine back to WT with 0.2% taurine. To examine which enzymes influence taurine concentrations in various tissues from WT and HO at 2 M, expression of five taurine-related enzymes, two antioxidant enzymes as well as lactoferrin (Lft) and prolactin receptor (Prlr) was determined using RT(2) qPCR. The expression of taurine transporter in the liver, brain, muscle and kidney from HO was increased except in the lung. Our data showed expression of glutamate decarboxylase-like 1(Gadl-1) was increased in the brain and muscle in HO

  14. Recent advances in understanding hepatic drug transport

    PubMed Central

    Stieger, Bruno; Hagenbuch, Bruno

    2016-01-01

    Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy. While many drug transporters are expressed in hepatocytes, and some of them are well characterized, several transporters have only recently been identified as new drug transporters. Novel powerful tools to deorphanize (drug) transporters are being applied and show promising results. Although a large set of tools are available for studying transport in vitro and in isolated cells, tools for studying transport in living organisms, including humans, are evolving now and rely predominantly on imaging techniques, e.g. positron emission tomography. Imaging is an area which, certainly in the near future, will provide important insights into "transporters at work" in vivo. PMID:27781095

  15. Effect of Liver Disease on Hepatic Transporter Expression and Function.

    PubMed

    Thakkar, Nilay; Slizgi, Jason R; Brouwer, Kim L R

    2017-09-01

    Liver disease can alter the disposition of xenobiotics and endogenous substances. Regulatory agencies such as the Food and Drug Administration and the European Medicines Evaluation Agency recommend, if possible, studying the effect of liver disease on drugs under development to guide specific dose recommendations in these patients. Although extensive research has been conducted to characterize the effect of liver disease on drug-metabolizing enzymes, emerging data have implicated that the expression and function of hepatobiliary transport proteins also are altered in liver disease. This review summarizes recent developments in the field, which may have implications for understanding altered disposition, safety, and efficacy of new and existing drugs. A brief review of liver physiology and hepatic transporter localization/function is provided. Then, the expression and function of hepatic transporters in cholestasis, hepatitis C infection, hepatocellular carcinoma, human immunodeficiency virus infection, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and primary biliary cirrhosis are reviewed. In the absence of clinical data, nonclinical information in animal models is presented. This review aims to advance the understanding of altered expression and function of hepatic transporters in liver disease and the implications of such changes on drug disposition. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    PubMed

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  17. Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis

    PubMed Central

    Burt, Howard J.; Riedmaier, Arian Emami; Harwood, Matthew D.; Crewe, H. Kim; Gill, Katherine L.

    2016-01-01

    This study aimed to derive quantitative abundance values for key hepatic transporters suitable for in vitro–in vivo extrapolation within a physiologically based pharmacokinetic modeling framework. A meta-analysis was performed whereby data on abundance measurements, sample preparation methods, and donor demography were collated from the literature. To define values for a healthy Caucasian population, a subdatabase was created whereby exclusion criteria were applied to remove samples from non-Caucasian individuals, those with underlying disease, or those with subcellular fractions other than crude membrane. Where a clinically relevant active genotype was known, only samples from individuals with an extensive transporter phenotype were included. Authors were contacted directly when additional information was required. After removing duplicated samples, the weighted mean, geometric mean, standard deviation, coefficient of variation, and between-study homogeneity of transporter abundances were determined. From the complete database containing 24 transporters, suitable abundance data were available for 11 hepatic transporters from nine studies after exclusion criteria were applied. Organic anion transporting polypeptides OATP1B1 and OATP1B3 showed the highest population abundance in healthy adult Caucasians. For several transporters, the variability in abundance was reduced significantly once the exclusion criteria were applied. The highest variability was observed for OATP1B3 > OATP1B1 > multidrug resistance protein 2 > multidrug resistance gene 1. No relationship was found between transporter expression and donor age. To our knowledge, this study provides the first in-depth analysis of current quantitative abundance data for a wide range of hepatic transporters, with the aim of using these data for in vitro–in vivo extrapolation, and highlights the significance of investigating the background of tissue(s) used in quantitative transporter proteomic studies. Similar

  18. Pharmacology of taurine.

    PubMed

    Oja, Simo S; Saransaari, Pirjo

    2007-01-01

    Taurine has a number of physiological functions, e.g., in cell volume regulation and inhibitory neuromodulation. Taurine and its derivatives have also been tested as potential pharmacological agents in many pathological states. We endeavor here to review the present status of this investigation. Taurine (2-aminoethanesulfonic acid) is a simple sulfur-containing amino acid present in virtually all cells throughout the animal kingdom. In particular, it is enriched in electrically excitable tissues such as brain, retina, heart and skeletal muscles. In the central nervous system, taurine has been implicated in two major phenomena; in cell volume regulation [1-3] and in inhibitory neuromodulation or neurotransmission [4-7]. Its function as a neurotransmitter implies the existence of specific taurine receptors and the neuromodulatory role, an interference with functions of other transmitter systems. There is scant evidence to corroborate the first assumption, but ample for the latter. In other tissues taurine has also been thought to act as an antioxidant in cell protection and to have beneficial effects on cardiovascular functions. These taurine properties are only partially explored so far but taurine and many of its derivatives have been tested as potential pharmaceutical agents in a number of pathological states.

  19. Enzymes of the taurine biosynthetic pathway are expressed in rat mammary gland.

    PubMed

    Ueki, Iori; Stipanuk, Martha H

    2007-08-01

    Taurine is the most abundant free amino acid in the body and is present at high concentrations during development and in the early milk. It is synthesized from cysteine via oxidation of cysteine to cysteinesulfinate by the enzyme cysteine dioxygenase (CDO), followed by the decarboxylation of cysteinesulfinate to hypotaurine, catalyzed by cysteine sulfinic acid decarboxylase (CSAD). To determine whether the taurine biosynthetic pathway is present in mammary gland and whether it is differentially expressed during pregnancy and lactation, and also to further explore the possible regulation of hepatic taurine synthesis during pregnancy and lactation, we measured mammary and hepatic CDO and CSAD mRNA and protein concentrations and tissue, plasma and milk taurine concentrations. CDO and CSAD mRNA and protein were expressed in mammary gland and liver regardless of physiological state. Immunohistochemistry demonstrated the expression of CDO in ductal cells of pregnant rats, but not in other mammary epithelial cells or in ductal cells of nonpregnant rats. CDO was also present in stromal adipocytes in mammary glands of both pregnant and nonpregnant rats. Our findings support an upregulation of taurine synthetic capacity in the mammary gland of pregnant rats, based on mammary taurine and hypotaurine concentrations and the intense immunohistochemical staining for CDO in ductal cells of pregnant rats. Hepatic taurine synthetic capacity, particularly CSAD, and taurine concentrations were highest in rats during the early stages of lactation, suggesting the liver may also play a role in the synthesis of taurine to support lactation or repletion of maternal reserves.

  20. Effect of taurine on mRNA expression of thioredoxin interacting protein in Caco-2 cells.

    PubMed

    Gondo, Yusuke; Satsu, Hideo; Ishimoto, Yoko; Iwamoto, Taku; Shimizu, Makoto

    2012-09-28

    Taurine (2-aminoethanesulfonic acid), a sulfur-containing β-amino acid, plays an important role in several essential biological processes; although, the underlying mechanisms for these regulatory functions remain to be elucidated, especially at the genetic level. We investigated the effects of taurine on the gene expression profile in Caco-2 cells using DNA microarray. Taurine increased the mRNA expression of thioredoxin interacting protein (TXNIP), which is involved in various metabolisms and diseases. β-Alanine or γ-aminobutyric acid (GABA), which are structurally or functionally related to taurine, did not increase TXNIP mRNA expression. These suggest the expression of TXNIP mRNA is induced specifically by taurine. β-Alanine is also known to be a substrate of taurine transporter (TAUT) and competitively inhibits taurine uptake. Inhibition of taurine uptake by β-alanine eliminated the up-regulation of TXNIP, which suggests TAUT is involved in inducing TXNIP mRNA expression. The up-regulation of TXNIP mRNA expression by taurine was also observed at the protein level. Furthermore, taurine significantly increased TXNIP promoter activity. Our present study demonstrated the taurine-specific phenomenon of TXNIP up-regulation, which sheds light on the physiological function of taurine. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Effect of sulfide, osmotic, and thermal stresses on taurine transporter mRNA levels in the gills of the hydrothermal vent-specific mussel Bathymodiolus septemdierum.

    PubMed

    Nakamura-Kusakabe, Ikumi; Nagasaki, Toshihiro; Kinjo, Azusa; Sassa, Mieko; Koito, Tomoko; Okamura, Kei; Yamagami, Shosei; Yamanaka, Toshiro; Tsuchida, Shinji; Inoue, Koji

    2016-01-01

    Hydrothermal vent environmental conditions are characterized by high sulfide concentrations, fluctuating osmolality, and irregular temperature elevations caused by vent effluents. These parameters represent potential stressors for organisms that inhabit the area around hydrothermal vents. Here, we aimed to obtain a better understanding of the adaptation mechanisms of marine species to hydrothermal vent environments. Specifically, we examined the effect of sulfide, osmolality, and thermal stress on the expression of taurine transporter (TAUT) mRNA in the gill of the deep-sea mussel Bathymodiolus septemdierum, which is a dominant species around hydrothermal vent sites. We analyzed TAUT mRNA levels by quantitative real-time polymerase chain reaction (PCR) in the gill of mussels exposed to sulfide (0.1 or 1mg/L Na2S·9H2O), hyper- (115% seawater) and hypo- (97.5%, 95.5%, and 85% seawater) osmotic conditions, and thermal stresses (12°C and 20°C) for 24 and 48h. The results showed that mussels exposed to relatively low levels of sulfide (0.1mg/L) and moderate heat stress (12°C) exhibited higher TAUT mRNA levels than the control. Although hyper- and hypo-osmotic stress did not significantly change TAUT mRNA levels, slight induction was observed in mussels exposed to low osmolality. Our results indicate that TAUT is involved in the coping mechanism of mussels to various hydrothermal vent stresses. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    SciTech Connect

    Das, Joydeep; Vasan, Vandana; Sil, Parames C.

    2012-01-15

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

  3. Taurine inhibits osteoblastic differentiation of vascular smooth muscle cells via the ERK pathway.

    PubMed

    Liao, Xiao-bo; Zhou, Xin-min; Li, Jian-ming; Yang, Jin-fu; Tan, Zhi-ping; Hu, Zhuo-wei; Liu, Wei; Lu, Ying; Yuan, Ling-qing

    2008-05-01

    Vascular calcification develops within atherosclerotic lesions and results from a process similar to osteogenesis. Taurine is a free beta-amino acid and plays an important physiological role in mammals. We have recently demonstrated that vascular smooth muscle cells (VSMCs) express a functional taurine transporter. To evaluate the possible role of taurine in vascular calcification, we assessed its effects on osteoblastic differentiation of VSMCs in vitro. The results showed that taurine inhibited the beta-glycerophosphate-induced osteoblastic differentiation of VSMCs as evidenced by both the decreasing alkaline phosphate (ALP) activity and expression of the core binding factor alpha1 (Cbfalpha1). Taurine also activated the extracellular signal-regulated protein kinase (ERK) pathway. Inhibition of ERK pathway reversed the effect of taurine on ALP activity and Cbfalpha1 expression. These results suggested that taurine inhibited osteoblastic differentiation of vascular cells via the ERK pathway.

  4. Extracellular taurine in the substantia nigra: taurine-glutamate interaction.

    PubMed

    García Dopico, José; Perdomo Díaz, Juan; Alonso, Teofilo Jorge; González Hernández, Tomás; Castro Fuentes, Rafael; Rodríguez Díaz, Manuel

    2004-05-15

    Taurine has been proposed as an inhibitory transmitter in the substantia nigra (SN), but the mechanisms involved in its release and uptake remain practically unexplored. We studied the extracellular pool of taurine in the rat's SN by using microdialysis methods, paying particular attention to the taurine-glutamate (GLU) interaction. Extracellular taurine increased after cell depolarization with high-K(+) in a Ca(2+)-dependent manner, being modified by the local perfusion of GLU, GLU receptor agonists, and zinc. Nigral administration of taurine increased the extracellular concentration of gamma-aminobutyric acid (GABA) and GLU, the transmitters of the two main inputs of the SN. The modification of the glial metabolism with fluocitrate and L-methionine sulfoximine also changed the extracellular concentration of taurine. The complex regulation of the extracellular pool of taurine, its interaction with GABA and GLU, and the involvement of glial cells in its regulation suggest a volume transmission role for taurine in the SN.

  5. Macitentan does not interfere with hepatic bile salt transport.

    PubMed

    Treiber, Alexander; Äänismaa, Päivi; de Kanter, Ruben; Delahaye, Stephane; Treher, Marianne; Hess, Patrick; Sidharta, Patricia

    2014-07-01

    Treatment of pulmonary arterial hypertension with the endothelin receptor antagonist bosentan has been associated with transient increases in liver transaminases. Mechanistically, bosentan inhibits the bile salt export pump (BSEP) leading to an intrahepatic accumulation of cytotoxic bile salts, which eventually results in hepatocellular damage. BSEP inhibition by bosentan is amplified by its accumulation in the liver as bosentan is a substrate of organic anion-transporting polypeptide (OATP) transport proteins. The novel endothelin receptor antagonist macitentan shows a superior liver safety profile. Introduction of the less acidic sulfamide moiety and increased lipophilicity yield a hepatic disposition profile different from other endothelin receptor antagonists. Passive diffusion rather than OATP-mediated uptake is the driving force for macitentan uptake into the liver. Interaction with the sodium taurocholate cotransporting polypeptide and BSEP transport proteins involved in hepatic bile salt homeostasis is therefore limited due to the low intrahepatic drug concentrations. Evidence for this conclusion is provided by in vitro experiments in drug transporter-expressing cell lines, acute and long-term studies in rats and dogs, absence of plasma bile salt changes in healthy human volunteers after multiple dosing, and finally the liver safety profile of macitentan in the completed phase III morbidity/mortality SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) trial. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Taurine and the renal system

    PubMed Central

    2010-01-01

    Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, taurine plays a role in the renal cell cycle and apoptosis, and functions as an osmolyte during the stress response. The role of the kidney in adaptation to variations in dietary taurine intake and the regulation of taurine body pool size are described. Finally, the protective function of taurine against several kidney diseases is reviewed. PMID:20804616

  7. Hepatic glutathione and glutathione S-conjugate transport mechanisms.

    PubMed Central

    Lee, T. K.; Li, L.; Ballatori, N.

    1997-01-01

    Glutathione (GSH) plays a critical role in many cellular processes, including the metabolism and detoxification of oxidants, metals, and other reactive electrophilic compounds of both endogenous and exogenous origin. Because the liver is a major site of GSH and glutathione S-conjugate biosynthesis and export, significant effort has been devoted to characterizing liver cell sinusoidal and canalicular membrane transporters for these compounds. Glutathione S-conjugates synthesized in the liver are secreted preferentially into bile, and recent studies in isolated canalicular membrane vesicles indicate that there are multiple transport mechanisms for these conjugates, including those that are energized by ATP hydrolysis and those that may be driven by the electrochemical gradient. Glutathione S-conjugates that are relatively hydrophobic or have a bulky S-substituent are good substrates for the canalicular ATP-dependent transporter mrp2 (multidrug resistance-associated protein 2, also called cMOAT, the canalicular multispecific organic anion transporter, or cMrp, the canalicular isoform of mrp). In contrast with the glutathione S-conjugates, hepatic GSH is released into both blood and bile. GSH transport across both of these membrane domains is of low affinity and is energized by the electrochemical potential. Recent reports describe two candidate GSH transport proteins for the canalicular and sinusoidal membranes (RcGshT and RsGshT, respectively); however, some concerns have been raised regarding these studies. Additional work is needed to characterize GSH transporters at the functional and molecular level. PMID:9626749

  8. Effects of taurine administration on exercise.

    PubMed

    Yatabe, Yoshihisa; Miyakawa, Shumpei; Ohmori, Hajime; Mishima, Hajime; Adachi, Takako

    2009-01-01

    Taurine concentration in rat skeletal muscles after endurance running, with and without taurine administration was studied. Taurine concentrations in skeletal muscles was significantly decreased in exercised groups without taurine administration. However, taurine administration reduced the decrease of taurine concentration in skeletal muscles in exercise. Oral administration of taurine has effect for maintaining taurine concentration in skeletal muscles in exercise. The duration of running time to exhaustion of rats, with and without taurine administration were studied. The duration of running time to exhaustion was significantly increased by taurine administration. Oral administration of taurine increases the ability of physical endurance. Rat urinary excretions of creatinine, creatine, 3-methylhistidine (3-MH) after treadmill running, with and without taurine administration were studied. Rat urinary excretions of creatinine, creatine, 3-MH after treadmill running was significantly decreased with taurine administration. Taurine administration was considered to reduce the exercise-induced muscle fatigue.

  9. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis.

    PubMed

    Das, Joydeep; Vasan, Vandana; Sil, Parames C

    2012-01-15

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Using quantitative intravital multiphoton microscopy to dissect hepatic transport in rats.

    PubMed

    Dunn, Kenneth W; Ryan, Jennifer C

    2017-09-01

    Hepatic solute transport is a complex process whose disruption is associated with liver disease and drug-induced liver injury. Intravital multiphoton fluorescence excitation microscopy provides the spatial and temporal resolution necessary to characterize hepatic transport at the level of individual hepatocytes in vivo and thus to identify the mechanisms and cellular consequences of cholestasis. Here we present an overview of the use of fluorescence microscopy for studies of hepatic transport in living animals, and describe how we have combined methods of intravital microscopy and digital image analysis to dissect the effects of drugs and pathological conditions on the function of hepatic transporters in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Taurine prevents ultraviolet B induced apoptosis in retinal ganglion cells.

    PubMed

    Dayang, Wu; Dongbo, Pang

    2017-06-07

    Compatible osmolytes accumulation is an active resistance response in retina under ultraviolet radiation and hypertonicity conditions. The purpose of this research is to investigate the protective role of taurine on retina under ultraviolet B radiation. Osmolytes transporters was measured by quantitative realtime PCR. Osmolytes uptake was estimated by radioimmunoassay. Cell viability was caculated by MTT assay. Cell apoptosis was measured by flow cytometry analysis. Hypertonicity accelerated osmolytes uptake into retinal ganglion cells including taurine, betaine and myoinositol. Ultraviolet B radiation increased osmolytes transporter expression and osmolytes uptake. In addition, osmolyte taurine remarkably prevented ultraviolet B radiation induced cell apoptosis in retinal ganglion cells. The effect of compatible osmolyte taurine on cell survival rate may play an important role in cell resistance and adaption to UVB exposure.

  12. Stimulatory effect of taurine on calcium ion uptake in rod outer segments of the rat retina is independent of taurine uptake.

    PubMed

    Militante, J D; Lombardini, J B

    1999-10-01

    Taurine stimulates ATP-dependent Ca(2+) uptake in the rat rod outer segments (ROS). This stimulation has been linked to the function of the cyclic nucleotide-gated cation channel, implying an important physiologic role for taurine in visual signal transduction. Calmodulin (CaM) has been reported to affect taurine transport in the choroid plexus and also to inhibit the cyclic nucleotide-gated channel; thus, the effects of the competitive CaM inhibitors trifluoperazine (TFP) and N-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide (J-8) were studied on Ca(2+) and taurine uptake in the rat ROS. Pretreatment of the ROS preparation with TFP and J-8 for 5 min before measurement of Ca(2+)-uptake activity produced inhibition of the effects of taurine on ATP-dependent Ca(2+) uptake. Both TFP and J-8 also were effective in inhibiting high-affinity taurine uptake. In both uptake systems, inhibition by TFP was noncompetitive. These data initially suggested that the stimulatory effects of taurine on ATP-dependent Ca(2+) uptake are dependent on taurine uptake. However, competitive inhibition of taurine uptake by guanidinoethane sulfonate did not produce any effect on the stimulatory effects of taurine. Previous studies have proposed that taurine binds directly to the plasma membrane, and our study demonstrated that TFP inhibits taurine binding to the ROS. In addition, our study demonstrated that taurine uptake is unaffected by varying the concentration of Ca(2+) and that the effects of TFP are independent of Ca(2+), suggesting that TFP acts through a CaM-independent mechanism.

  13. Hepatic mitochondrial glutathione: transport and role in disease and toxicity

    SciTech Connect

    Fernandez-Checa, Jose C. . E-mail: checa229@yahoo.com; Kaplowitz, Neil . E-mail: kaplowitz@hsc.usc.edu

    2005-05-01

    Synthesized in the cytosol of cells, a fraction of cytosolic glutathione (GSH) is then transported into the mitochondrial matrix where it reaches a high concentration and plays a critical role in defending mitochondria against oxidants and electrophiles. Evidence mainly from kidney and liver mitochondria indicated that the dicarboxylate and the 2-oxoglutarate carriers contribute to the transport of GSH across the mitochondrial inner membrane. However, differential features between kidney and liver mitochondrial GSH (mGSH) transport seem to suggest the existence of additional carriers the identity of which remains to be established. One of the characteristic features of the hepatic mitochondrial transport of GSH is its regulation by membrane fluidity. Conditions leading to increased cholesterol deposition in the mitochondrial inner membrane such as in alcohol-induced liver injury decrease membrane fluidity and impair the mitochondrial transport of GSH. Depletion of mitochondrial GSH by alcohol is believed to contribute to the sensitization of the liver to alcohol-induced injury through tumor necrosis factor (TNF)-mediated hepatocellular death. Through control of mitochondrial electron transport chain-generated oxidants, mitochondrial GSH modulates cell death and hence its regulation may be a key target to influence disease progression and drug-induced cell death.

  14. Analysis of hyposmolarity-induced taurine efflux pathways in the bullfrog sympathetic ganglia.

    PubMed

    Sakai, S; Tosaka, T

    1999-03-01

    Hyposmolarity-induced taurine release was dependent on the decrease in medium osmolarity (5-50%) in the satellite glial cells of the bullfrog sympathetic ganglia. Release of GABA induced by hyposmolarity was much less than that of taurine. Omission of external Cl- replaced with gluconate totally suppressed taurine release, but only slightly suppressed GABA release. Bumetanide and furosemide, blockers of the Na+/K+/2Cl- cotransport system, inhibited taurine release by about 40%. Removal of external Na+ by replacement with choline, or omission of K+, suppressed taurine release by 40%. Antagonists of the Cl-/HCO3 exchange system, SITS, DIDS and niflumic acid, significantly reduced taurine release. The carbonic anhydrase inhibitor, acetazolamide, reduced the taurine release by 34%. Omission of external HCO3 by replacement with HEPES caused a 40% increase in the hyposmolarity-induced taurine release. Hyposmolarity-induced GABA release was not affected by bumetanide or SITS. Chloride channel blockers, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and N-phenylanthranilic acid (DPC), practically abolished taurine release. Blockers of K+ channels, clofilium and quinidine, had no effect on the taurine release. The hyposmolarity-induced taurine release was considerably enhanced by a simultaneous increase in external K+. GABA was not mediated by the same transport pathway as that of taurine. These results indicate that Cl- channels may be responsible for the hyposmolarity-induced taurine release, and that Na+/K+/2Cl- cotransporter and Cl-/HCO3 exchanger may contribute to maintain the intracellular Cl- levels higher than those predicted for a passive thermodynamic distribution in the hyposmolarity-induced taurine release.

  15. The effect of long-term taurine supplementation and fructose feeding on glucose and lipid homeostasis in Wistar rats.

    PubMed

    Larsen, Lea Hüche; Orstrup, Laura Kofoed Hvidsten; Hansen, Svend Høime; Grunnet, Niels; Quistorff, Bjørn; Mortensen, Ole Hartvig

    2013-01-01

    The nonprotein amino acid taurine has been shown to counteract the negative effects of a high-fructose diet in rats with regard to insulin resistance and dyslipidemia. Here we examined the long-term (26 weeks) effects of oral taurine supplementation (2% in the drinking water) in fructose-fed Wistar rats.The combination of fructose and taurine caused a significant increase in fasting glucose compared to the control diet without changing hepatic phosphoenol pyruvate carboxykinase mRNA levels. The combination of fructose and taurine also improved glucose tolerance compared to control. Neither a high-fructose diet nor taurine supplementation induced significant changes in body weight, body fat or total calorie intake, fasting insulin levels, HOMA-IR, or insulin-induced Akt phosphorylation in skeletal muscle.Fructose alone caused a decrease in liver triglyceride content, with taurine supplementation preventing this. There was no effect of long-term fructose diet and/or taurine supplementation on plasma triglycerides, plasma nonesterified fatty acids, as well as plasma HDL, LDL, and total cholesterol.In conclusion, the study suggests that long-term taurine supplementation improves glucose tolerance and normalize hepatic triglyceride content following long-term fructose feeding. However, as the combination of taurine and fructose also increased fasting glucose levels, the beneficial effect of taurine supplementation towards amelioration of glucose intolerance and insulin resistance may be questionable.

  16. Ontogenetic taurine biosynthesis ability in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Wang, Xuan; He, Gen; Mai, Kangsen; Xu, Wei; Zhou, Huihui

    2015-07-01

    Taurine (2-aminoethane sulfonic acid) plays important roles in multiple physiological processes including osmoregulation, bile salt conjugation and membrane protection. It is known that taurine biosynthesis varies in different fish species. However, its ontogenetic regulation has not been clear. In the present study, we found that the hepatic concentrations of taurine increased marginally with rainbow trout growth. The mRNA expression, protein levels and enzyme activities of key enzymes involved in taurine biosynthesis, cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD), were analyzed. Our results showed that the mRNA levels and protein abundances of CSD increased dramatically with the development of rainbow trout stages while the enzyme activities showed a slight improvement. However, the expression and activities of CDO decreased with rainbow trout growth. These results provide valuable information on defining the exact supplementation of taurine in diets for different stages of rainbow trout and give new insights into elucidating the regulation of taurine metabolism in rainbow trout. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Long-lasting enhancement of corticostriatal neurotransmission by taurine.

    PubMed

    Chepkova, A N; Doreulee, N; Yanovsky, Y; Mukhopadhyay, D; Haas, H L; Sergeeva, O A

    2002-10-01

    Taurine occurs at high concentrations in the forebrain and its distribution varies with (patho)physiological conditions; however, its role in neural function is poorly understood. We have now characterized its effects on corticostriatal synaptic transmission. Bath application of taurine (10 mm) to slices obtained from mice and rats exerted a biphasic action on corticostriatal field potentials. The fast and reversible inhibition by taurine was accompanied by a depolarization and conductance increase in medium spiny neurons and was sensitive to gamma-aminobutyric acid (GABA)A and glycine receptor (GlyR) antagonists. A long-lasting enhancement (LLETAU) of field potentials was recorded after taurine withdrawal. The LLETAU was not prevented by N-methyl-d-aspartate (NMDA)- or by GABAA receptor-antagonists, but was sensitive to the GlyR-antagonist strychnine and blocked by the competitive taurine uptake inhibitor guanidinoethylsulphonate (GES, 1 mm). GES at 10 mm evoked an enhancement of field potentials similar to LLETAU. LLETAU depended on protein kinase C activation as it was blocked by chelerythrine, but was unaffected by trifluoperazine, and thus independent of calmodulin. LLETAU was significantly smaller in juvenile than in mature rodents. Activation of GlyRs and the specific taurine transporter by taurine evoke a long-lasting enhancement of corticostriatal transmission.

  18. The cytoprotective role of taurine in exercise-induced muscle injury.

    PubMed

    Dawson, R; Biasetti, M; Messina, S; Dominy, J

    2002-06-01

    Intense exercise is thought to increase oxidative stress and damage muscle tissue. Taurine is present in high concentration in skeletal muscle and may play a role in cellular defenses against free radical-mediated damage. The aim of this study was to determine if manipulating muscle levels of taurine would alter markers of free radical damage after exercise-induced injury. Adult male Sprague-Dawley rats were supplemented via the drinking water with either 3% (w/v) taurine (n = 10) or the competitive taurine transport inhibitor, beta-alanine (n = 10), for one month. Controls (n = 20) drank tap water containing 0.02% taurine and all rats were placed on a taurine free diet. All the rats except one group of sedentary controls (n = 10) were subjected to 90 minutes of downhill treadmill running. Markers of cellular injury and free radical damage were determined along with tissue amino acid content. The 3% taurine treatment raised plasma levels about 2-fold and 3% beta-alanine reduced plasma taurine levels about 50%. Taurine supplementation (TS) significantly increased plasma glutamate levels in exercised rats. Exercise reduced plasma methionine levels and taurine prevented its decline. Taurine supplementation increased muscle taurine content significantly in all muscles except the soleus. beta-alanine decreased muscle taurine content about 50% in all the muscles examined. Lipid peroxidation (TBARS) was significantly increased by exercise in the extensor digitorium longus (EDL) and gastrocnemius (GAST) muscles. Both taurine and beta-alanine completely blocked the increase in TBARs in the EDL, but had no effect in the GAST. Muscle content of the cytosolic enzyme, lactate dehydrogenase (LDH) was significantly decreased by exercise in the GAST muscle and this effect was attenuated by both taurine and beta-alanine. Muscle myeloperoxidase (MPO) activity was significantly elevated in the gastrocnemius muscle, but diet had no effect. MPO activity was significantly increased by

  19. Effect of beta-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content.

    PubMed

    Jong, Chian Ju; Ito, Takashi; Mozaffari, Mahmood; Azuma, Junichi; Schaffer, Stephen

    2010-08-24

    The beta-amino acid, taurine, is a nutritional requirement in some species. In these species, the depletion of intracellular stores of taurine leads to the development of severe organ dysfunction. The basis underlying these defects is poorly understood, although there is some suggestion that oxidative stress may contribute to the abnormalities. Recent studies indicate that taurine is required for normal mitochondrial protein synthesis and normal electron transport chain activity; it is known that defects in these events can lead to severe mitochondrial oxidative stress. The present study examines the effect of taurine deficiency on the first step of mitochondrial protein synthesis regulation by taurine, namely, the formation of taurinomethyluridine containing tRNA. Isolated rat cardiomyocytes were rendered taurine deficient by incubation with medium containing the taurine transport inhibitor, beta-alanine. The time course of cellular and mitochondrial taurine depletion was measured. The primer extension method was employed to evaluate the effect of beta-alanine treatment on taurinomethyluridine content of tRNALeu. The protein levels of ND6 were also determined by Western blot analysis. beta-alanine caused a time-dependent decrease in cellular taurine content, which were reduced in half after 48 hrs of incubation. The amount of taurine in the mitochondria was considerably less than that in the cytosol and was unaffected by beta-alanine treatment. Approximately 70% of the tRNALeu in the untreated cell lacked taurinomethyluridine and these levels were unchanged following beta-alanine treatment. Protein content of ND6, however, was significantly reduced after 48 hours incubation with beta-alanine. The taurine levels of the cytosol and the mitochondria are not directly coupled. The beta-alanine-mediated reduction in taurine levels is too small to affect taurinomethyluridine levels. Nonetheless, it interferes with mitochondrial protein synthesis, as exemplified by a

  20. Taurine decreased uric acid levels in hyperuricemic rats and alleviated kidney injury.

    PubMed

    Feng, Ying; Sun, Fang; Gao, Yongchao; Yang, Jiancheng; Wu, Gaofeng; Lin, Shumei; Hu, Jianmin

    2017-07-29

    Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes

    PubMed Central

    Yang, Y J; Han, Y Y; Chen, K; Zhang, Y; Liu, X; Li, S; Wang, K Q; Ge, J B; Liu, W; Zuo, J

    2015-01-01

    Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult. PMID:26673669

  2. TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes.

    PubMed

    Yang, Y J; Han, Y Y; Chen, K; Zhang, Y; Liu, X; Li, S; Wang, K Q; Ge, J B; Liu, W; Zuo, J

    2015-12-17

    Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult.

  3. Dietary taurine supplementation prevents glial alterations in retina of diabetic rats.

    PubMed

    Zeng, Kaihong; Xu, Hongxia; Mi, Mantian; Zhang, Qianyong; Zhang, Yajie; Chen, Ka; Chen, Fang; Zhu, Jundong; Yu, Xiaoping

    2009-02-01

    The preventive effect of dietary taurine supplementation on glial alterations in retina of streptozotocin-induced diabetic rats was examined in this study. Blood glucose content, content of taurine, glutamate and -amino butyric acid (GABA) and expression of glial fibrillary acid protein (GFAP), vascular endothelial growth factor (VEGF), glutamate transporter (GLAST), glutamine synthetase (GS) and glutamate decarboxylase (GAD) in retina were determined in diabetic rats fed without or with 5% taurine in a controlled trial lasting 12 weeks, with normal rats fed without or with 5% taurine served as controls. Dietary taurine supplementation could not lower glucose concentration in blood (P > 0.05), but caused an elevation of taurine content and a decline in levels of glutamate and GABA in retina of diabetic rats (P < 0.05). The content of GABA in normal control group was not altered by taurine supplementation. With supplementation of taurine in diet, lower expression of GFAP and VEGF while higher expression of GLAST, GS and GAD in retina of diabetic rats were determinated by RT-PCR, Western-blotting and immunofluorescence (P < 0.05). GFAP, VEGF, GLAST, GS and GAD expressions in normal controls were not altered by taurine treatment. This may have prospective implications of using taurine to treat complications in diabetic retinopathy.

  4. Endogenous synthesis of taurine and GABA in rat ocular tissues.

    PubMed

    Heinämäki, A A

    1988-01-01

    The endogenous production of taurine and gamma-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine in the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye.

  5. Is taurine a functional nutrient?

    PubMed

    Bouckenooghe, Thomas; Remacle, Claude; Reusens, Brigitte

    2006-11-01

    Taurine, a free amino acid, is found in millimolar concentrations in most mammalian tissues. Mammals are able to synthesize taurine endogenously, but some species such as humans are more dependent on dietary sources of taurine. A growing body of evidence suggests that taurine plays a preponderant role in many physiological processes, which will be summarized in this review. Evidence for the requirement of taurine in the human diet has been obtained in many studies involving animal models and a few clinical trials. Recent and past studies suggested that taurine might be a pertinent candidate for use as a nutritional supplement to protect against oxidative stress, neurodegenerative diseases or atherosclerosis. Taurine has demonstrated promising actions in vitro, and as a result clinical trials have begun to investigate its effects on various diseases. Taurine appears to have multiple functions and plays an important role in many physiological processes, such as osmoregulation, immunomodulation and bile salt formation. Taurine analogues/derivatives have recently been reported to have a marked activity on various disorders. Taken together, these observations actualize the old story of taurine.

  6. Expression of taurine transporter is regulated through the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway and contributes to cytoprotection in HepG2 cells.

    PubMed

    Ito, Takashi; Fujio, Yasushi; Hirata, Mayo; Takatani, Tomoka; Matsuda, Takahisa; Muraoka, Satoko; Takahashi, Kyoko; Azuma, Junichi

    2004-08-15

    In hypertonic environment, taurine accumulates in cells via activation of TauT (taurine transporter) as an adaptive regulation. Recent studies revealed that TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway regulated the expression of various molecules which protect cells against hypertonic stress. In the present study, we investigated the osmoregulatory mechanisms of TauT expression. TauT was up-regulated at both functional and transcriptional levels in HepG2 under hypertonic condition. The TonE site was identified in the promoter region of TauT gene. Reporter gene assay revealed that promoter activity was increased under hypertonic conditions, whereas deletion or mutation of TonE sequence abolished the induction of the promoter activity in response to hypertonicity. By using the reporter gene plasmids containing a TonE site of TauT promoter (p2xTonE-Luc), it was demonstrated that a TonE site was sufficient for the hypertonicity-mediated activation of TauT promoter. Importantly, co-transfection of TauT promoter gene plasmid with wild-type TonEBP expression vector enhanced promoter activity under isotonic conditions, whereas dominant-negative TonEBP abrogated the TauT promoter activity induced by hypertonicity. Finally, treatment with taurine prevented HepG2 cells from cell death induced by hypertonic medium. These findings suggested that induction of TauT by hypertonicity is mediated by the activation of the TonE/TonEBP pathway and confers resistance to hypertonic stress.

  7. Expression of taurine transporter is regulated through the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway and contributes to cytoprotection in HepG2 cells

    PubMed Central

    2004-01-01

    In hypertonic environment, taurine accumulates in cells via activation of TauT (taurine transporter) as an adaptive regulation. Recent studies revealed that TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway regulated the expression of various molecules which protect cells against hypertonic stress. In the present study, we investigated the osmoregulatory mechanisms of TauT expression. TauT was up-regulated at both functional and transcriptional levels in HepG2 under hypertonic condition. The TonE site was identified in the promoter region of TauT gene. Reporter gene assay revealed that promoter activity was increased under hypertonic conditions, whereas deletion or mutation of TonE sequence abolished the induction of the promoter activity in response to hypertonicity. By using the reporter gene plasmids containing a TonE site of TauT promoter (p2xTonE-Luc), it was demonstrated that a TonE site was sufficient for the hypertonicity-mediated activation of TauT promoter. Importantly, co-transfection of TauT promoter gene plasmid with wild-type TonEBP expression vector enhanced promoter activity under isotonic conditions, whereas dominant-negative TonEBP abrogated the TauT promoter activity induced by hypertonicity. Finally, treatment with taurine prevented HepG2 cells from cell death induced by hypertonic medium. These findings suggested that induction of TauT by hypertonicity is mediated by the activation of the TonE/TonEBP pathway and confers resistance to hypertonic stress. PMID:15142033

  8. Swelling-activated taurine and creatine effluxes from rat cortical astrocytes are pharmacologically distinct.

    PubMed

    Bothwell, J H; Styles, P; Bhakoo, K K

    2002-01-15

    Primary cultures of rat cortical astrocytes undergo a swelling-activated loss of taurine and creatine. In this study, the pharmacological characteristics of the taurine and creatine efflux pathways were compared, and significant differences were shown to exist between the two. Both taurine and creatine effluxes were rapidly activated upon exposure of astrocytes to hypo-osmotic media, and rapidly inactivated upon their return to iso-osmotic media. The relative rates of taurine and creatine efflux depended upon the magnitude of the hypo-osmotic shock. Anion-transport inhibitors strongly inhibited taurine efflux, with the order of potency being NPPB > DIDS > niflumic acid. DIDS and NPPB had less of an inhibitory effect on creatine efflux, whereas tamoxifen and niflumic acid actually stimulated creatine efflux. These data are consistent with separate pathways for taurine and creatine loss during astrocyte swelling.

  9. Hepatic expression and cellular distribution of the glucose transporter family

    PubMed Central

    Karim, Sumera; Adams, David H; Lalor, Patricia F

    2012-01-01

    Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. However there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required. PMID:23239915

  10. Taurine rescues hippocampal long-term potentiation from ammonia-induced impairment.

    PubMed

    Chepkova, Aisa N; Sergeeva, Olga A; Haas, Helmut L

    2006-09-01

    Hyperammonemia, a major pathophysiological factor in hepatic encephalopathy, impairs long-term potentiation (LTP) of synaptic transmission, a cellular model of learning and memory, in the hippocampus. We have now studied the protective action of taurine on this paradigm by analyzing LTP characteristics in mouse hippocampal slices treated with ammonium chloride (1 mM) in the presence of taurine (1 mM), an ubiquitous osmolyte, antioxidant, and neuromodulator, as well as other substances with such properties. Ammonia-treated slices displayed a significant impairment of LTP maintenance. Taurine and the mitochondrial enhancer l-carnitine, but not the antioxidants (ascorbate, carnosine, and the novel compound GVS-111) or the osmolyte betaine prevented this impairment. The protective effect of taurine was preserved under the blockade of inhibitory GABA(A) and glycine receptors. It is suggested that taurine may rescue the mechanisms of hippocampal synaptic plasticity by improving mitochondrial function under hyperammonemic conditions.

  11. Hyperinsulinemia Enhances Hepatic Expression of the Fatty Acid Transporter Cd36 and Provokes Hepatosteatosis and Hepatic Insulin Resistance.

    PubMed

    Steneberg, Pär; Sykaras, Alexandros G; Backlund, Fredrik; Straseviciene, Jurate; Söderström, Ingegerd; Edlund, Helena

    2015-07-31

    Hepatosteatosis is associated with the development of both hepatic insulin resistance and Type 2 diabetes. Hepatic expression of Cd36, a fatty acid transporter, is enhanced in obese and diabetic murine models and human nonalcoholic fatty liver disease, and thus it correlates with hyperinsulinemia, steatosis, and insulin resistance. Here, we have explored the effect of hyperinsulinemia on hepatic Cd36 expression, development of hepatosteatosis, insulin resistance, and dysglycemia. A 3-week sucrose-enriched diet was sufficient to provoke hyperinsulinemia, hepatosteatosis, hepatic insulin resistance, and dysglycemia in CBA/J mice. The development of hepatic steatosis and insulin resistance in CBA/J mice on a sucrose-enriched diet was paralleled by increased hepatic expression of the transcription factor Pparγ and its target gene Cd36 whereas that of genes implicated in lipogenesis, fatty acid oxidation, and VLDL secretion was unaltered. Additionally, we demonstrate that insulin, in a Pparγ-dependent manner, is sufficient to directly increase Cd36 expression in perfused livers and isolated hepatocytes. Mouse strains that display low insulin levels, i.e. C57BL6/J, and/or lack hepatic Pparγ, i.e. C3H/HeN, do not develop hepatic steatosis, insulin resistance, or dysglycemia on a sucrose-enriched diet, suggesting that elevated insulin levels, via enhanced CD36 expression, provoke fatty liver development that in turn leads to hepatic insulin resistance and dysglycemia. Thus, our data provide evidence for a direct role for hyperinsulinemia in stimulating hepatic Cd36 expression and thus the development of hepatosteatosis, hepatic insulin resistance, and dysglycemia.

  12. Effect of taurine in rat milk on the growth of offspring.

    PubMed

    Hu, J M; Rho, J Y; Suzuki, M; Nishihara, M; Takahashi, M

    2000-07-01

    The physiological significance of taurine in milk in the growth of rat pups was investigated. Our results confirmed that taurine was at an exceptionally high concentration in rat milk during the lactational period, especially for the first few days after birth. Pups taking no milk from natural dams but from foster mothers at an advanced lactational period showed a slower growth rate. Intraperitoneal administration of taurine to the foster mothers in the first five days restored this growth retardation. On the other hand, intraperitoneal administration of beta-alanine, a transport antagonist of taurine, to the natural dams through the lactational period induced a slower growth rate of pups. This beta-alanine treatment to dams increased beta-alanine concentration, but did not decrease taurine concentrations in milk, and serum taurine concentration in the pups receiving this milk was elevated. Direct administration of beta-alanine to pups also increased the serum taurine concentrations dose-dependently. Beta-alanine administration to pups significantly decreased [3H]taurine incorporation into all the organs examined, and in contrast. [3H]taurine concentrations in serum and urine were elevated. Thus, beta-alanine inhibited taurine incorporation into cells and accelerated taurine excretion into either urine or milk. Serum IGF-I levels in pups receiving beta-alanine either directly or via their mothers was significantly lower than those in control pups. Cumulatively, taurine ingestion from milk at an early lactational period seems critical for normal growth of rat neonates due to its role in maintaining normal serum IGF-I levels.

  13. Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus.

    PubMed

    Jia, Fan; Yue, Minerva; Chandra, Dev; Keramidas, Angelo; Goldstein, Peter A; Homanics, Gregg E; Harrison, Neil L

    2008-01-02

    Taurine is one of the most abundant free amino acids in the brain. In a number of studies, taurine has been reported to activate glycine receptors (Gly-Rs) at moderate concentrations (> or = 100 microM), and to be a weak agonist at GABA(A) receptors (GABA(A)-Rs), which are usually activated at high concentrations (> or = 1 mM). In this study, we show that taurine reduced the excitability of thalamocortical relay neurons and activated both extrasynaptic GABA(A)-Rs and Gly-Rs in neurons in the mouse ventrobasal (VB) thalamus. Low concentrations of taurine (10-100 microM) decreased neuronal input resistance and firing frequency, and elicited a steady outward current under voltage clamp, but had no effects on fast inhibitory synaptic currents. Currents elicited by 50 microM taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 microM Zn2+, consistent with the pharmacological properties of extrasynaptic GABA(A)-Rs (alpha4beta2delta subtype) involved in tonic inhibition in the thalamus. Tonic inhibition was enhanced by an inhibitor of taurine transport, suggesting that taurine can act as an endogenous activator of these receptors. Taurine-evoked currents were absent in relay neurons from GABA(A)-R alpha4 subunit knock-out mice. The amplitude of the taurine current was larger in neurons from adult mice than juvenile mice. Taurine was a more potent agonist at recombinant alpha4beta2delta GABA(A)-Rs than at alpha1beta2gamma2 GABA(A)-Rs. We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABA(A)-Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus.

  14. Taurine plays an important role in the protection of spermatogonia from oxidative stress.

    PubMed

    Higuchi, Masato; Celino, Fritzie T; Shimizu-Yamaguchi, Sonoko; Miura, Chiemi; Miura, Takeshi

    2012-12-01

    It has been demonstrated that taurine has various physiological functions in the body. We demonstrated that taurine is abundant in the serum, liver, muscle and testis of the Japanese eel (Anguilla japonica). In the eel testis, taurine is found mainly in spermatogonia and is weakly expressed also in the Sertoli cells. We have further found in the eel testis that taurine is actively accumulated via the sodium/chloride-dependent taurine transporter (TauT; SLC6A6), which is expressed in germ cells. In our current study, the effects of taurine on the anti-oxidant response were examined. Taurine was found to promote the total superoxide dismutase (SOD) activity in the testis. Moreover, our results indicate that taurine does not affect the mRNA levels of copper-zinc (Cu/Zn) SOD or manganese SOD, but promotes the translation of Cu/Zn SOD. Overall, our present data suggest that taurine may modulate Cu/Zn SOD at the translational level and thereby may play an important role in the protection of germ cells from oxidative stress.

  15. Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice.

    PubMed

    Ito, Takashi; Yoshikawa, Natsumi; Inui, Takaaki; Miyazaki, Natsuko; Schaffer, Stephen W; Azuma, Junichi

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is found in milimolar concentrations in mammalian tissues. One of its main functions is osmoregulation; however, it also exhibits cytoprotective activity by diminishing injury caused by stress and disease. Taurine depletion is associated with several defects, many of which are found in the aging animal, suggesting that taurine might exert anti-aging actions. Therefore, in the present study, we examined the hypothesis that taurine depletion accelerates aging by reducing longevity and accelerating aging-associated tissue damage. Tissue taurine depletion in taurine transporter knockout (TauTKO) mouse was found to shorten lifespan and accelerate skeletal muscle histological and functional defects, including an increase in central nuclei containing myotubes, a reduction in mitochondrial complex 1 activity and an induction in an aging biomarker, Cyclin-dependent kinase 4 inhibitor A (p16INK4a). Tissue taurine depletion also enhances unfolded protein response (UPR), which may be associated with an improvement in protein folding by taurine. Our data reveal that tissue taurine depletion affects longevity and cellular senescence; an effect possibly linked to a disturbance in protein folding.

  16. Taurine in neonatal nutrition - revisited

    USDA-ARS?s Scientific Manuscript database

    Taurine (2-aminoethanesulfonic acid) was isolated from ox (Bos Taurus) bile in 1827 but, until the mid to late 1970, it was thought to be merely a by-product of sulfur amino and metabolism. In 1975, it was noted that taurine deficiency in cats was associated with retinal degeneration which was reve...

  17. Regulation of hepatic bile acid transporters Ntcp and Bsep expression

    PubMed Central

    Cheng, Xingguo; Buckley, David; Klaassen, Curtis D.

    2009-01-01

    Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression at parturition. After birth, mouse Ntcp and Bsep mRNA decreased by more than 50%, and then gradually increased to adult levels by day 30. Expression of mouse Ntcp mRNA and protein exhibit higher levels in female than male livers, which is consistent with the trend of human NTCP mRNA expression between men and women. No gender difference exists in BSEP/Bsep expression in human and mouse livers. Hormone replacements conducted in gonadectomized, hypophysectomized, and lit/lit mice indicate that female-predominant Ntcp expression in mouse liver is due to the inhibitory effect of male-pattern GH secretion, but not sex hormones. Ntcp and Bsep expression are in general resistant to induction by a large battery of microsomal enzyme inducers. Administration of cholestyramine increased Ntcp, whereas chenodeoxycholic acid increased Bsep mRNA expression. In silico analysis indicates that female-predominant mouse and human Ntcp/NTCP expression may be due to GH. In conclusion, mouse Ntcp and Bsep are regulated by age, gender, cholestyramine, and bile acid, but resistant to induction by most microsomal enzyme inducers. PMID:17897632

  18. Hepatitis

    MedlinePlus

    ... CPR: A Real Lifesaver Kids Talk About: Coaches Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... have liver damage because of it. What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  19. Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses.

    PubMed

    Nagai, Katsuhito; Fukuno, Shuhei; Oda, Ayano; Konishi, Hiroki

    2016-01-01

    The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses.

  20. A simple assay of taurine concentrations in food and biological samples using taurine dioxygenase.

    PubMed

    Matsuda, Motoki; Asano, Yasuhisa

    2012-08-15

    Taurine demonstrates various physiological functions and pharmacological actions. A successful application of taurine dioxygenase (EC 1.14.11.17) for taurine determination is described. The gene encoding taurine dioxygenase was cloned from Escherichia coli strain K-12, and the enzyme was used to determine taurine in commercially available beverages and some biological samples. The measured values obtained using the current method are close to the declared values with the precolumn derivatization ultra-performance liquid chromatography (UPLC) procedure. Taurine dioxygenase can be used for taurine determination in food control, biological research, and diagnoses based on urinary taurine concentration. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Taurine and skeletal muscle disorders.

    PubMed

    Conte Camerino, Diana; Tricarico, Domenico; Pierno, Sabata; Desaphy, Jean-François; Liantonio, Antonella; Pusch, Michael; Burdi, Rosa; Camerino, Claudia; Fraysse, Bodvael; De Luca, Annamaria

    2004-01-01

    Taurine is abundantly present in skeletal muscle. We give evidence that this amino acid exerts both short-term and long-term actions in the control of ion channel function and calcium homeostasis in striated fibers. Short-term actions can be estimated as the ability of this amino acid to acutely modulate both ion channel gating and the function of the structures involved in calcium handling. Long-term effects can be disclosed in situations of tissue taurine depletion and are likely related to the ability of the intracellular taurine to control transducing pathways as well as homeostatic and osmotic equilibrium in the tissue. The two activities are strictly linked because the intracellular level of taurine modulates the sensitivity of skeletal muscle to the exogenous application of taurine. Myopathies in which ion channels are directly or indirectly involved, as well as inherited or acquired pathologies characterized by metabolic alterations and change in calcium homeostasis, are often correlated with change in muscle taurine concentration and consequently with an enhanced therapeutic activity of this amino acid. We discuss both in vivo and in vitro evidence that taurine, through its ability to control sarcolemmal excitability and muscle contractility, can prove beneficial effects in many muscle dysfunctions.

  2. Mechanism for modulation of gating of connexin26-containing channels by taurine

    PubMed Central

    Kieken, Fabien; Tao, Liang; Sorgen, Paul L.; Harris, Andrew L.

    2011-01-01

    The mechanisms of action of endogenous modulatory ligands of connexin channels are largely unknown. Previous work showed that protonated aminosulfonates (AS), notably taurine, directly and reversibly inhibit homomeric and heteromeric channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32 channels. The present study investigated the molecular mechanisms of connexin channel modulation by taurine, using hemichannels and junctional channels composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28–amino acid “tag” to the carboxyl-terminal domain (CT) of Cx26 (Cx26T) eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells and liposomes. Cleavage of all but four residues of the tag (Cx26Tc) resulted in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine inhibition of heteromeric hemichannels (Cx26Tc/Cx32). Taurine actions on junctional channels were fully consistent with those on hemichannels. Taurine-induced inhibition of Cx26/Cx32T and nontagged Cx26 junctional channels was blocked by extracellular HEPES, a blocker of the taurine transporter, confirming that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic resonance of peptides corresponding to Cx26 cytoplasmic domains showed that taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL directly interact. ELISA showed that taurine disrupts a pH-dependent interaction between the CT and the CT-proximal half of the CL. These studies reveal that AS disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing channels, causing closure, and that the Cx26CT has a modulatory role in Cx26 function. PMID:21844220

  3. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model.

    PubMed

    Zhang, Zeyu; Liu, Dan; Yi, Bo; Liao, Zhangping; Tang, Lei; Yin, Dong; He, Ming

    2014-11-01

    We previously demonstrated that iron overload induces liver damage by causing the formation of reactive oxygen species (ROS). Taurine is a potent free radical scavenger that attenuates the damage caused by excessive oxygen free radicals. Therefore, the aim of the present study was to investigate whether taurine could reduce the hepatotoxicity of iron overload with regard to ROS production. Mice were intraperitoneally injected with iron 5 days/week for 13 weeks to achieve iron overload. It was found that iron overload resulted in liver dysfunction, increased apoptosis and elevated oxidative stress. Taurine supplementation increased liver taurine levels by 40% and led to improved liver function, as well as a reduction in apoptosis, ROS formation and mitochondrial swelling and an attenuation in the loss of the mitochondrial membrane potential. Treatment with taurine mediated a reduction in oxidative stress in iron‑overloaded mice, attenuated liver lipid peroxidation, elevated antioxidant enzyme activities and maintained reduced glutathione levels. These results indicate that taurine reduces iron‑induced hepatic oxidative stress, preserves liver function and inhibits hepatocyte apoptosis. Therefore, taurine may be a potential therapeutic drug to reduce liver damage caused by iron overload.

  4. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model

    PubMed Central

    ZHANG, ZEYU; LIU, DAN; YI, BO; LIAO, ZHANGPING; TANG, LEI; YIN, DONG; HE, MING

    2014-01-01

    We previously demonstrated that iron overload induces liver damage by causing the formation of reactive oxygen species (ROS). Taurine is a potent free radical scavenger that attenuates the damage caused by excessive oxygen free radicals. Therefore, the aim of the present study was to investigate whether taurine could reduce the hepatotoxicity of iron overload with regard to ROS production. Mice were intraperitoneally injected with iron 5 days/week for 13 weeks to achieve iron overload. It was found that iron overload resulted in liver dysfunction, increased apoptosis and elevated oxidative stress. Taurine supplementation increased liver taurine levels by 40% and led to improved liver function, as well as a reduction in apoptosis, ROS formation and mitochondrial swelling and an attenuation in the loss of the mitochondrial membrane potential. Treatment with taurine mediated a reduction in oxidative stress in iron-overloaded mice, attenuated liver lipid peroxidation, elevated antioxidant enzyme activities and maintained reduced glutathione levels. These results indicate that taurine reduces iron-induced hepatic oxidative stress, preserves liver function and inhibits hepatocyte apoptosis. Therefore, taurine may be a potential therapeutic drug to reduce liver damage caused by iron overload. PMID:25201602

  5. Reciprocal regulation between taurine and glutamate response via Ca2+- dependent pathways in retinal third-order neurons

    PubMed Central

    2010-01-01

    Although taurine and glutamate are the most abundant amino acids conducting neural signals in the central nervous system, the communication between these two neurotransmitters is largely unknown. This study explores the interaction of taurine and glutamate in the retinal third-order neurons. Using specific antibodies, both taurine and taurine transporters were localized in photoreceptors and Off-bipolar cells, glutamatergic neurons in retinas. It is possible that Off-bipolar cells release juxtaposed glutamate and taurine to activate the third-order neurons in retina. The interaction of taurine and glutamate was studied in acutely dissociated third-order neurons in whole-cell patch-clamp recording and Ca2+ imaging. We find that taurine effectively reduces glutamate-induced Ca2+ influx via ionotropic glutamate receptors and voltage-dependent Ca2+ channels in the neurons, and the effect of taurine was selectively inhibited by strychnine and picrotoxin, but not GABA receptor antagonists, although GABA receptors are present in the neurons. A CaMKII inhibitor partially reversed the effect of taurine, suggesting that a Ca2+/calmodulin-dependent pathway is involved in taurine regulation. On the other hand, a rapid influx of Ca2+ through ionotropic glutamate receptors could inhibit the amplitude and kinetics of taurine-elicited currents in the third-order neurons, which could be controlled with intracellular application of BAPTA a fast Ca2+ chelator. This study indicates that taurine is a potential neuromodulator in glutamate transmission. The reciprocal inhibition between taurine and glutamate in the postsynaptic neurons contributes to computation of visual signals in the retinal neurons. PMID:20804625

  6. Taurine buffers glutamate homeostasis in retinal cells in vitro under hypoxic conditions.

    PubMed

    Chen, Fang; Mi, Mantian; Zhang, Qianyong; Wei, Na; Chen, Ka; Xu, Hongxia; Yuan, Jialin; Zhou, Yong; Lang, Haibin; Yu, Xiaoping; Wang, Bin; Wang, Jian; Tang, Yong; Chang, Hui

    2010-01-01

    We investigated whether taurine indirectly protects neurons under hypoxia by affecting retinal Müller cells, which are known to play important roles in the regulation of retinal glutamate content. Retinal cells isolated from rats were exposed to hypoxia for 24 h. We evaluated the retinal neuron survival, glutamate content in cultures with and without taurine under hypoxic conditions. The glutamate clearance function correlated with the expression of glutamine synthetase (GS) mRNA and L-glutamate/L-aspartate transporter (GLAST) mRNA. Immunohistochemical staining of glial fibrillary acidic protein (GFAP), vimentin and S-100 protein was performed to examine cytoskeletal changes in retinal Müller cells. Retinal neurons treated with taurine exhibited significantly higher survival rates than those without taurine under hypoxia. Taurine inhibited the upregulation of GFAP and vimentin, and inhibited the downregulation of GLAST, GS and the nuclear-cytoplasmic ratio of S-100 under hypoxia. In addition, taurine inhibited the upregulation of the glutamate content in neurons and retinal Müller cells upon hypoxic exposure. These data suggest that hypoxic damage to cultured retinal cells is decreased by taurine. The neuroprotection by taurine may relate to buffering glutamate homeostasis via modulation of the glutamate clearance by retinal Müller cells. Copyright 2010 S. Karger AG, Basel.

  7. Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells.

    PubMed

    Gaucher, David; Arnault, Emilie; Husson, Zoé; Froger, Nicolas; Dubus, Elisabeth; Gondouin, Pauline; Dherbécourt, Diane; Degardin, Julie; Simonutti, Manuel; Fouquet, Stéphane; Benahmed, M A; Elbayed, K; Namer, Izzie-Jacques; Massin, Pascale; Sahel, José-Alain; Picaud, Serge

    2012-11-01

    In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion cells were degenerating in parallel to cone photoreceptors. The aim of this study was to re-assess a classic mouse model of taurine deficiency following a treatment with guanidoethane sulfonate (GES), a taurine transporter inhibitor to determine whether retinal ganglion cells are also affected. GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase. At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway. A change in the autofluorescence appearance of the eye fundus was explained on histological sections by an increased autofluorescence of the retinal pigment epithelium. Although the general morphology of the retina was not affected, cell damages were indicated by the general increase in glial fibrillary acidic protein expression. When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20 %) as the number of retinal ganglion cells (19 %). An abnormal synaptic plasticity of rod bipolar cell dendrites was also observed in GES-treated mice. These results indicate that taurine deficiency can not only lead to photoreceptor degeneration but also to retinal ganglion cell loss. Cone photoreceptors and retinal ganglion cells appear as the most sensitive cells to taurine deficiency. These results may explain the recent therapeutic interest of taurine in retinal degenerative pathologies.

  8. Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow.

    PubMed

    Wang, Qin; Fan, Weijia; Cai, Ying; Wu, Qiaoli; Mo, Lidong; Huang, Zhenwu; Huang, Huiling

    2016-09-01

    In mammalian tissues, taurine is an important natural component and the most abundant free amino acid in the heart, retina, skeletal muscle, brain, and leukocytes. This study is to examine the taurine's protective effects on neuronal ultrastructure, the function of the mitochondrial respiratory chain complex, and on cerebral blood flow (CBF). The model of traumatic brain injury (TBI) was made for SD rats by a fluid percussion device, with taurine (200 mg/kg) administered by tail intravenous injection once daily for 7 days after TBI. It was found that CBF was improved for both left and right brain at 30 min and 7 days post-injury by taurine. Reaction time was prolonged relative to the TBI-only group. Neuronal damage was prevented by 7 days taurine. Mitochondrial electron transport chain complexes I and II showed greater activity with the taurine group. The improvement by taurine of CBF may alleviate edema and elevation in intracranial pressure. Importantly taurine improved the hypercoagulable state.

  9. Taurine inhibits interleukin-6 expression and release induced by ultraviolet B exposure to human retinal pigment epithelium cells.

    PubMed

    Dayang, Wu; Jinsong, Zhang

    2015-01-01

    The massive uptake of compatible osmolytes is a self-protective response shared by retina exposed to hypertonic stress and ultraviolet stress. This study aimed to investigate the protective effects of taurine against ultraviolet damage in human retinal pigment epithelium cells. Real-time PCR, radioimmunoassay, ELISA and immunoassay were used to measure osmolyte uptake and IL-6 expression. Compared with normotonic stress, hypertonic stress led to an induction of osmolyte uptake including betaine, myoinositol and taurine. UVB exposure upregulated osmolyte transporter mRNA expression and increased osmolyte uptake respectively. Especially, taurine suppressed UVB-induced IL-6 mRNA expression significantly. The accumulation of IL-6 in UVB-exposed human retinal pigment epithelial cells supernatant was much slower when the cells were preincubated with taurine. Moreover, taurine suppressed IL-6 concentration in aqueous humour. The effect of compatible osmolyte taurine on IL-6 expression and release may play an important role in cell resistance and adaption to UVB exposure.

  10. Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

    PubMed

    Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D

    2016-07-01

    Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease.

  11. Hepatitis

    MedlinePlus

    ... clotting problems or chronic liver disease. previous continue Hepatitis B and Hepatitis C Although hep A is a ... does — through direct contact with infected body fluids. Hepatitis B and C are even more easily passed in ...

  12. Hepatitis

    MedlinePlus

    ... A if they've been vaccinated against it. Hepatitis B Hepatitis B is a more serious infection. It may lead ... of which cause severe illness and even death. Hepatitis B virus (HBV) is transmitted from person to person ...

  13. Hepatitis

    MedlinePlus

    ... a problem with the liver itself What Is Hepatitis A? Hepatitis A virus (HAV) is contagious, usually spreading to others ... objects contaminated by feces (poop) containing HAV. The hepatitis A vaccine has helped to make the infection rare ...

  14. Transporter-Enzyme Interplay: Deconvoluting Effects of Hepatic Transporters and Enzymes on Drug Disposition Using Static and Dynamic Mechanistic Models.

    PubMed

    Varma, Manthena V; El-Kattan, Ayman F

    2016-07-01

    A large body of evidence suggests hepatic uptake transporters, organic anion-transporting polypeptides (OATPs), are of high clinical relevance in determining the pharmacokinetics of substrate drugs, based on which recent regulatory guidances to industry recommend appropriate assessment of investigational drugs for the potential drug interactions. We recently proposed an extended clearance classification system (ECCS) framework in which the systemic clearance of class 1B and 3B drugs is likely determined by hepatic uptake. The ECCS framework therefore predicts the possibility of drug-drug interactions (DDIs) involving OATPs and the effects of genetic variants of SLCO1B1 early in the discovery and facilitates decision making in the candidate selection and progression. Although OATP-mediated uptake is often the rate-determining process in the hepatic clearance of substrate drugs, metabolic and/or biliary components also contribute to the overall hepatic disposition and, more importantly, to liver exposure. Clinical evidence suggests that alteration in biliary efflux transport or metabolic enzymes associated with genetic polymorphism leads to change in the pharmacodynamic response of statins, for which the pharmacological target resides in the liver. Perpetrator drugs may show inhibitory and/or induction effects on transporters and enzymes simultaneously. It is therefore important to adopt models that frame these multiple processes in a mechanistic sense for quantitative DDI predictions and to deconvolute the effects of individual processes on the plasma and hepatic exposure. In vitro data-informed mechanistic static and physiologically based pharmacokinetic models are proven useful in rationalizing and predicting transporter-mediated DDIs and the complex DDIs involving transporter-enzyme interplay. © 2016, The American College of Clinical Pharmacology.

  15. Importance of Hepatic Transporters in Clinical Disposition of Drugs and Their Metabolites.

    PubMed

    Patel, Mitesh; Taskar, Kunal S; Zamek-Gliszczynski, Maciej J

    2016-07-01

    This review provides a practical clinical perspective on the relevance of hepatic transporters in pharmacokinetics and drug-drug interactions (DDIs). Special emphasis is placed on transporters with clear relevance to clinical DDIs, efficacy, and safety. Basolateral OATP1B1 and 1B3 emerged as important hepatic drug uptake pathways, sites for systemic DDIs, and sources of pharmacogenetic variability. As the first step in hepatic drug removal from the circulation, OATPs are an important determinant of systemic pharmacokinetics, specifically influencing systemic absorption, clearance, and hepatic distribution for subsequent metabolism and/or excretion. Biliary excretion of parent drugs is a less prevalent clearance pathway than metabolism or urinary excretion, but BCRP and MRP2 are critically important to biliary/fecal elimination of drug metabolites. Inhibition of biliary excretion is typically not apparent at the level of systemic pharmacokinetics but can markedly increase liver exposure. Basolateral efflux transporters MRP3 and MRP4 mediate excretion of parent drugs and, more commonly, polar metabolites from hepatocytes into blood. Basolateral excretion is an area in need of further clinical investigation, which will necessitate studies more complex than just systemic pharmacokinetics. Clinical relevance of hepatic uptake is relatively well appreciated, and clinical consequences of hepatic excretion (biliary and basolateral) modulation remain an active research area. © 2016, The American College of Clinical Pharmacology.

  16. Role of Mitochondria and Endoplasmic Reticulum in Taurine-Deficiency-Mediated Apoptosis.

    PubMed

    Jong, Chian Ju; Ito, Takashi; Prentice, Howard; Wu, Jang-Yen; Schaffer, Stephen W

    2017-07-25

    Taurine is a ubiquitous sulfur-containing amino acid found in high concentration in most tissues. Because of its involvement in fundamental physiological functions, such as regulating respiratory chain activity, modulating cation transport, controlling inflammation, altering protein phosphorylation and prolonging lifespan, taurine is an important nutrient whose deficiency leads to severe pathology and cell death. However, the mechanism by which taurine deficiency causes cell death is inadequately understood. Therefore, the present study examined the hypothesis that overproduction of reactive oxygen species (ROS) by complex I of the respiratory chain triggers mitochondria-dependent apoptosis in hearts of taurine transporter knockout (TauTKO) mice. In support of the hypothesis, a 60% decrease in mitochondrial taurine content of 3-month-old TauTKO hearts was observed, which was associated with diminished complex I activity and the onset of mitochondrial oxidative stress. Oxidative damage to stressed mitochondria led to activation of a caspase cascade, with stimulation of caspases 9 and 3 prevented by treatment of 3-month-old TauTKO mice with the mitochondria specific antioxidant, MitoTempo. In 12 month-old, but not 3-month-old, TauTKO hearts, caspase 12 activation contributes to cell death, revealing a pathological role for endoplasmic reticulum (ER) stress in taurine deficient, aging mice. Thus, taurine is a cytoprotective nutrient that ensures normal mitochondrial and ER function, which is important for the reduction of risk for apoptosis and premature death.

  17. Effect of β-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content

    PubMed Central

    2010-01-01

    Background The β-amino acid, taurine, is a nutritional requirement in some species. In these species, the depletion of intracellular stores of taurine leads to the development of severe organ dysfunction. The basis underlying these defects is poorly understood, although there is some suggestion that oxidative stress may contribute to the abnormalities. Recent studies indicate that taurine is required for normal mitochondrial protein synthesis and normal electron transport chain activity; it is known that defects in these events can lead to severe mitochondrial oxidative stress. The present study examines the effect of taurine deficiency on the first step of mitochondrial protein synthesis regulation by taurine, namely, the formation of taurinomethyluridine containing tRNA. Methods Isolated rat cardiomyocytes were rendered taurine deficient by incubation with medium containing the taurine transport inhibitor, β-alanine. The time course of cellular and mitochondrial taurine depletion was measured. The primer extension method was employed to evaluate the effect of β-alanine treatment on taurinomethyluridine content of tRNALeu. The protein levels of ND6 were also determined by Western blot analysis. Results β-alanine caused a time-dependent decrease in cellular taurine content, which were reduced in half after 48 hrs of incubation. The amount of taurine in the mitochondria was considerably less than that in the cytosol and was unaffected by β-alanine treatment. Approximately 70% of the tRNALeu in the untreated cell lacked taurinomethyluridine and these levels were unchanged following β-alanine treatment. Protein content of ND6, however, was significantly reduced after 48 hours incubation with β-alanine. Conclusions The taurine levels of the cytosol and the mitochondria are not directly coupled. The β-alanine-mediated reduction in taurine levels is too small to affect taurinomethyluridine levels. Nonetheless, it interferes with mitochondrial protein synthesis

  18. Dietary taurine deficiency and dilated cardiomyopathy in the fox.

    PubMed

    Moise, N S; Pacioretty, L M; Kallfelz, F A; Stipanuk, M H; King, J M; Gilmour, R F

    1991-02-01

    Taurine deficiency has been implicated as a potential cause of dilated cardiomyopathy. However, the relationship between taurine and myocardial function is presently unclear. The purpose of this study was to determine whether dilated cardiomyopathy in the fox is associated with dietary taurine deficiency. A total of 68 foxes from farms with a history of death caused by dilated cardiomyopathy and 14 foxes from a farm with no history of dilated cardiomyopathy were studied. Dilated cardiomyopathy was diagnosed by echocardiography in 48% of the foxes from one farm with a positive history and in none of the foxes from the control farm. Foxes less than 9 months of age were more commonly affected than older foxes (p = 0.03). Plasma taurine concentrations were significantly less (p less than 0.01) in foxes that had dilated cardiomyopathy (26.8 +/- 16.4 nmol/ml) than in the control foxes (99.3 +/- 60.2 nmol/ml). A significantly higher (p less than 0.01) incidence of dilated cardiomyopathy was present in foxes with a history of a sibling or offspring that died of dilated cardiomyopathy than in foxes without a family history of cardiac death. In one fox with dilated cardiomyopathy that was tested, the myocardial taurine concentration was lower (1.7 mumol/gm wet weight) than that of control foxes (7.3 +/- 1.6 mumol/gm wet weight). Hepatic cysteinesulfinic acid decarboxylase activity was significantly less (p less than 0.001) in foxes with dilated cardiomyopathy (0.97 +/- 0.2 nmol/mm.mg protein) than in control foxes (2.11 +/- 0.07 nmol CO2/mm.mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

  20. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

  1. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

  2. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

  3. Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection.

    PubMed

    Hinoshita, E; Taguchi, K; Inokuchi, A; Uchiumi, T; Kinukawa, N; Shimada, M; Tsuneyoshi, M; Sugimachi, K; Kuwano, M

    2001-12-01

    To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.

  4. Taurine Protects Lens Epithelial Cells Against Ultraviolet B-Induced Apoptosis.

    PubMed

    Dayang, Wu; Dongbo, Pang

    2017-10-01

    The massive uptake of compatible osmolytes is a self-protective response shared by lens exposed to hypertonic stress and ultraviolet stress. This study aimed to investigate the protective effects of taurine against ultraviolet B-induced cytotoxicity in the lens epithelial cells. Real-time PCR was used to measure osmolytes transport. Radioimmunoassay was used to measure osmolytes uptake. Cell counting kit-8 assays were used to measure cellular viability. Flow cytometry analysis was used to measure apoptosis level. Compared with normotonic stress, hypertonic stress-induced osmolytes uptake into the lens epithelial cells such as betaine, myoinositol and taurine. UVB exposure increased osmolytes transporter mRNA expression together with osmolytes uptake. Moreover, taurine suppressed UVB-induced cell apoptosis in the lens epithelial cells significantly. The effect of compatible osmolyte taurine on cell survival rate may play an important role in cell resistance and adaption to UVB exposure.

  5. Ontogeny of Human Hepatic and Intestinal Transporter Gene Expression during Childhood: Age Matters

    PubMed Central

    Mooij, Miriam G.; Schwarz, Ute I.; de Koning, Barbara A. E.; Leeder, J. Steven; Gaedigk, Roger; Samsom, Janneke N.; Spaans, Edwin; van Goudoever, Johannes B.; Tibboel, Dick; Kim, Richard B.

    2014-01-01

    Many drugs prescribed to children are drug transporter substrates. Drug transporters are membrane-bound proteins that mediate the cellular uptake or efflux of drugs and are important to drug absorption and elimination. Very limited data are available on the effect of age on transporter expression. Our study assessed age-related gene expression of hepatic and intestinal drug transporters. Multidrug resistance protein 2 (MRP2), organic anion transporting polypeptide 1B1 (OATP1B1), and OATP1B3 expression was determined in postmortem liver samples (fetal n = 6, neonatal n = 19, infant n = 7, child n = 2, adult n = 11) and multidrug resistance 1 (MDR1) expression in 61 pediatric liver samples. Intestinal expression of MDR1, MRP2, and OATP2B1 was determined in surgical small bowel samples (neonates n = 15, infants n = 3, adults n = 14). Using real-time reverse-transcription polymerase chain reaction, we measured fetal and pediatric gene expression relative to 18S rRNA (liver) and villin (intestines), and we compared it with adults using the 2−∆∆Ct method. Hepatic expression of MRP2, OATP1B1, and OATP1B3 in all pediatric age groups was significantly lower than in adults. Hepatic MDR1 mRNA expression in fetuses, neonates, and infants was significantly lower than in adults. Neonatal intestinal expressions of MDR1 and MRP2 were comparable to those in adults. Intestinal OATP2B1 expression in neonates was significantly higher than in adults. We provide new data that show organ- and transporter-dependent differences in hepatic and intestinal drug transporter expression in an age-dependent fashion. This suggests that substrate drug absorption mediated by these transporters may be subject to age-related variation in a transporter dependent pattern. PMID:24829289

  6. Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

    PubMed Central

    Brandoni, Anabel; Hazelhoff, María Herminia; Bulacio, Romina Paula; Torres, Adriana Mónica

    2012-01-01

    Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct. The absorption, distribution and elimination of drugs are impaired during this pathology. Prolonged cholestasis may alter both liver and kidney function. Lactam antibiotics, diuretics, non-steroidal anti-inflammatory drugs, several antiviral drugs as well as endogenous compounds are classified as organic anions. The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds. It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions. The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis, such as multidrug resistance-associated protein 2, organic anion transporting polypeptide 1, organic anion transporter 3, bilitranslocase, bromosulfophthalein/bilirubin binding protein, organic anion transporter 1 and sodium dependent bile salt transporter. The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions. PMID:23197884

  7. Taurine release modified by GABAergic agents in hippocampal slices from adult and developing mice.

    PubMed

    Saransaari, P; Oja, S S

    2000-01-01

    In order to characterize the possible regulation of taurine release by GABAergic terminals, the effects of several agonists and antagonists of GABA receptors on the basal and K+-stimulated release of [3H]taurine were investigated in hippocampal slices from adult (3-month-old) and developing (7-day-old) mice using a superfusion system. Taurine release was concentration-dependently potentiated by GABA, which effect was reduced by phaclofen, saclofen and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) at both ages, suggesting regulation by both GABA(B) and GABA(C) receptors. The involvement of GABA(A) receptors could not be excluded since the antagonist bicuculline was able to affect both basal and K+-evoked taurine release. Furthermore, several GABA(B) receptor effectors were able to inhibit K+-stimulated taurine release in the adults, while the GABA(C) receptor agonists trans-4-aminocrotonic acid (TACA) and cis-4-aminocrotonic acid (CACA) potentiated this release. The potentiation of taurine release by agents acting on the three types of GABA receptors in both adult and developing hippocampus further indicates the involvement of transporters operating in an outward direction. This inference is corroborated by the moderate but significant inhibition of taurine uptake by the same compounds.

  8. Taurine restores Axl/Gas6 expression in vascular smooth muscle cell calcification model.

    PubMed

    Liao, Xiao-Bo; Peng, Yi-Qun; Zhou, Xin-Min; Yang, Bing; Zheng, Zhe; Liu, Li-Ming; Song, Feng-Lin; Li, Jian-Ming; Zhou, Kang; Meng, Ji-Cai; Yuan, Ling-Qing; Xie, Hui

    2010-07-01

    Our previous studies demonstrated that taurine inhibits osteoblastic differentiation of vascular smooth muscular cells (VSMCs) via the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, but the underlying mechanism is not elucidated. The tyrosine kinase receptor Axl and its ligand growth arrest-specific protein 6 (Gas6) are expressed in VSMCs. Axl/Gas6 signaling system is known to inhibit VSMCs calcification. We herein showed that taurine partially restored Axl and Gas6 expression in beta-glycerophosphate (beta-GP)-induced VSMC calcification model. Taurine also induced activation of ERK, but not other two MAPKs including c-jun N-terminal Kinase (JNK) and p38 in VSMCs. Either knockdown of the taurine transporter (TAUT) or treatment with the ERK-specific inhibitor PD98059 blocked the activation of ERK by taurine and abolished taurine-induced Axl/Gas6 expression and calcium deposition reduction in beta-GP-induced VSMC calcification model. These results demonstrate for the first time that taurine stimulates expression of Axl and Gas6 via TAUT/ERK signaling pathway in beta-GP-induced VSMC calcification model.

  9. Regulation of Human Hepatic Drug Transporter Activity and Expression by Diesel Exhaust Particle Extract

    PubMed Central

    Le Vee, Marc; Jouan, Elodie; Stieger, Bruno; Lecureur, Valérie; Fardel, Olivier

    2015-01-01

    Diesel exhaust particles (DEPs) are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe) may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC) uptake transporters organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC) efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT) 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP), whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP). Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a reference activator of the aryl hydrocarbon receptor (AhR) pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute to their

  10. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

    PubMed

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase(+) was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. Copyright © 2015 Elsevier Inc

  11. Protective role of taurine against genotoxic damage in mice treated with methotrexate and tamoxfine.

    PubMed

    Alam, Sally S; Hafiz, Nagla A; Abd El-Rahim, Abeer H

    2011-01-01

    The genotoxic actions of anti-neoplastic drugs can lead to the development of secondary cancers in patients in extended remission. One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury. We investigated the modulatory effects of exogenously administered taurine, on the genotoxicity of two well known anti-neoplastic drugs methotrexate (MTX) and tamoxifen (TAM) in Swiss albino mice. The animals were randomly divided into six groups consisting of ten mice each. Two groups were received single intraperitoneal injection of MTX (10 mg/kgb.wt.) and TAM (50 mg/kgb.wt.) to induce genotoxicity. Two other groups were treated orally with taurine (100 mg/kgb.wt.) for nine days prior to MTX and TAM administration. A vehicle treated control group and taurine control groups were also included. The protective effects of taurine were monitored by apoptosis assays and level of reduced glutathione (GSH), a key antioxidant, in liver, chromosomal aberrations in somatic and germ cells as well as sperm count, motility and morphology. The results indicated that taurine pre-treatment showed significant increment in the levels of GSH content, reduction in DNA fragmentation and ladder formation in hepatic tissue, suggesting the antioxidant activity of taurine may reduce the toxic effects of MTX and TAM. Treatment with taurine showed also significant reduction in the frequency of chromosomal aberrations in both somatic and germ cells. Moreover, it increases sperm count and motility, and decreases the incidence of sperm abnormalities. In conclusion, it appears that taurine protects against anti-neoplastic drugs-induced genotoxicity in somatic and germ tissues and may be of therapeutic potential in alleviating the risk of secondary tumors in chemotherapy.

  12. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

    PubMed Central

    Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.

    2011-01-01

    The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160

  13. The Taurine Content of Japanese Seaweed.

    PubMed

    Kawasaki, Azusa; Ono, Ayuko; Mizuta, Shoshi; Kamiya, Mitsunobu; Takenaga, Takaaki; Murakami, Shigeru

    2017-01-01

    Japanese and South Koreans have a dietary habit of eating seaweed. Although it is known that some seaweed contains taurine, there have been few detailed analyses on the taurine content of seaweed other than the major types of edible seaweed. In the present study, we determined the content of free amino acids, including taurine, in seaweed obtained along the Sea of Japan coast. The taurine content in the seaweed varied according to the species. Among the 29 different types of seaweed that were studied, red algae contained relatively high concentrations of taurine. In contrast, the taurine content was low or undetectable in brown and green algae. The algal alanine level was relatively higher in brown sea algae, which was in sharp contrast to its taurine level. No clear trends were observed with regards to the distribution of the other free amino acids, including aspartic acid, glutamic acid, and phenylalanine. Considering the physiological role of taurine in cellular homeostasis, the algal taurine content may be associated with the growing environment. Taurine-rich red edible algae such as mafunori (Gloiopeltis tenax)/fukurofunori (Gloiopeltis furcata), kabanori (Gracilaria textorii), and ogonori (Gracilaria vermiculophylla) may be used to create functional foods that are rich in naturally occurring taurine.

  14. Hypolipidemic action of taurine in rats.

    PubMed

    Gandhi, V M; Cherian, K M; Mulky, M J

    1992-05-01

    The effect of taurine on the serum and liver cholesterol and triglyceride levels was studied in rats fed cholesterol plus cholic acid. Four groups of 4 weeks old rats were fed control diet, hypercholesterolemic diet (HCD), HCD + 1% taurine or HCD + 2% taurine for 8 weeks. Addition of taurine in HCD diet showed a significant reduction not only in serum total cholesterol and triglyceride levels but also in liver total cholesterol, lipid and triglyceride contents compared to the animals fed HCD alone. Histological examination of organs of these animals showed severe fatty vacuolation in livers and signet ring type vacuolation in kidneys of rats fed HCD. Taurine showed ameliorating effect on these abnormalities. The animals fed taurine in HCD also showed increased bile and sterol excretion in faeces compared to rats fed HCD alone. Taurine showed significant hypocholesterolemia in rats probably by enhancing the catabolism of cholesterol and reducing the absorption of dietary cholesterol.

  15. Taurine Supplementation Improves Functional Capacity, Myocardial Oxygen Consumption, and Electrical Activity in Heart Failure.

    PubMed

    Ahmadian, Mehdi; Dabidi Roshan, Valiollah; Ashourpore, Eadeh

    2017-07-04

    Taurine is an amino acid found abundantly in the heart in very high concentrations. It is assumed that taurine contributes to several physiological functions of mammalian cells, such as osmoregulation, anti-inflammation, membrane stabilization, ion transport modulation, and regulation of oxidative stress and mitochondrial protein synthesis. The objective of the current study was to evaluate the effectiveness of taurine supplementation on functional capacity, myocardial oxygen consumption, and electrical activity in patients with heart failure. In a double-blind and randomly designed study, 16 patients with heart failure were assigned to two groups: taurine (TG, n = 8) and placebo (PG, n = 8). TG received 500-mg taurine supplementation three times per day for two weeks. Significant decrease in the values of Q-T segments (p < 0.01) and significant increase in the values of P-R segments (p < 0.01) were detected following exercise post-supplementation in TG rather than in PG. Significantly higher values of taurine concentration, T wave, Q-T segment, physical capacities, and lower values of cardiovascular capacities were detected post-supplementation in TG as compared with PG (all p values <0.01). Taurine significantly enhanced the physical function and significantly reduced the cardiovascular function parameters following exercise. Our results also suggest that the short-term taurine supplementation is an effective strategy for improving some selected hemodynamic parameters in heart failure patients. Together, these findings support the view that taurine improves cardiac function and functional capacity in patients with heart failure. This idea warrants further study.

  16. Cellular taurine release triggered by stimulation of the Fas(CD95) receptor in Jurkat lymphocytes.

    PubMed

    Lang, F; Madlung, J; Uhlemann, A C; Risler, T; Gulbins, E

    1998-08-01

    One of the hallmarks of apoptosis is cell shrinkage which appears to be important for cell death. The mechanisms mediating cell volume decrease have, however, not been addressed. Mechanisms employed by swollen cells to decrease their cell volume include activation of ion transport pathways, such as ion channels and KCl cotransport, and release of cellular osmolytes, such as taurine, sorbitol, betaine and inositol. The present study has been performed to test for release of taurine. To this end Jurkat human T-lymphocytes were loaded with [3H]taurine and apoptotic cell death induced by triggering the Fas(CD95) receptor with monoclonal crosslinking antibody. Triggering the Fas(CD95) receptor led to a release of 60+/-5% of cellular taurine within 90 min. The release did not occur prior to 45 min. The release coincided with cell shrinkage as evidenced from forward scatter in FACS analysis and preceeded DNA fragmentation according to propidium iodide staining. The delay of taurine release was not influenced by exchange of medium and thus was not due to extracellular accumulation of a stimulator. The Fas(CD95)-induced taurine release, cell shrinkage and DNA fragmentation were blunted by lowering of ambient temperature to 23 degreesC. Following pretreatment of cells with Fas(CD95) antibody at 23 degreesC rewarming led to rapid taurine release, cell shrinkage and DNA fragmentation, indicating that the temperature-sensitive step is distal to the mechanisms accounting for the delay. Osmotic cell swelling led to an immediate release of taurine. In conclusion, Fas(CD95) triggering leads to delayed taurine release through a temperature-sensitive mechanism.

  17. Role of taurine in spinal cord injury.

    PubMed

    Gupta, R C; Seki, Y; Yosida, J

    2006-08-01

    Taurine is a sulfur amino acid. It is found endogenously in human and several others tissues. It is significantly in high concentration in mammals. Human body contains about 0.1% of body weight as taurine. It has a number of physiological and pharmacological actions. It is also used in the therapy of important organs dysfunctions. In spinal cord it has inhibitory effects; like antiepileptic and anti-nociceptive. Taurine also inhibits substance p induced biting and scratching behavior. In spinal cord injury elevated level of taurine has been observed. Higher level of taurine has been also recorded in SCI therapy using, known clinical agent methyl prednisolone (MP). The increased taurine concentration seems to be involved in protection and regeneration of tissues following injury. In SCI along with physical injury secondary activities also takes place which are complex in nature. Secondary activity includes vascular events and activation of neutrophils, resulting endothelial damage. Activated neutrophils; release a variety of inflammatory mediators such as myeloperoxidase (MPO), reactive oxygen species (ROS), and some others. It is believed that taurine exert its protective action through scavenging of ROS and down regulating several other inflammatory mediators like tumor necrosis factors (TNFalpha). The inside of mechanism reveals toxic substance HOCl is produced by MPO is converted to less toxic substances through scavenging action of taurine. Amino acid therapy has its own limitations and to over come such situation there is a need to develop small, simple lipophilic analogs of taurine. Use of taurine analogs has provided better results; for example, N- chloro taurine (NCT) which is a taurine derivative has exhibited therapeutic advances over taurine. Taurine and its analogs with sound experimental and clinical support may constitute a new class of therapeutic agents for SCI., and perhaps this review may provide enough material to think of this.

  18. Dietary fish oil stimulates hepatic low density lipoprotein transport in the rat.

    PubMed Central

    Ventura, M A; Woollett, L A; Spady, D K

    1989-01-01

    These studies were undertaken to examine the effect of fish oil, safflower oil, and hydrogenated coconut oil on the major processes that determine the concentration of low density lipoprotein (LDL) in plasma, i.e., the rate of LDL production and the rates of receptor-dependent and receptor-independent LDL uptake in the various organs of the body. When fed at the 20% level, fish oil reduced plasma LDL-cholesterol levels by 38% primarily by increasing LDL receptor activity in the liver. Dietary safflower oil also increased hepatic LDL receptor activity; however, since the rate of LDL production also increased, plasma LDL-cholesterol levels remained essentially unchanged. Hydrogenated coconut oil had no effect on LDL receptor activity but increased the rate of LDL-cholesterol production causing plasma LDL-cholesterol levels to increase 46%. Dietary fish oil had no effect on the receptor-dependent transport of asialofetuin by the liver, suggesting that the effect of fish oil on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physical properties of hepatic membranes. Finally, dietary fish oil increased hepatic cholesteryl ester levels and suppressed hepatic cholesterol synthesis rates, suggesting that the up-regulation of hepatic LDL receptor activity in these animals was not simply a response to diminished cholesterol availability in the liver. PMID:2760200

  19. Modeling O2 transport within engineered hepatic devices.

    PubMed

    McClelland, Randall E; MacDonald, Jeffrey M; Coger, Robin N

    2003-04-05

    Predicting and improving oxygen transport within bioartificial liver (BAL) devices continues to be an important engineering challenge since oxygen is one of the critical nutrients necessary for maintaining hepatocyte viability and function. Such a computational model would not only help predict outcomes but it would also allow system modifications to be analyzed prior to developing experimental protocols. This would help to facilitate future design improvements while reducing both experimental time and capital resource costs, and is the focus of the current study. Specifically, a computational model of O(2) transport through collagen and microporous collagen ECMs is analyzed for hollow fiber (HF), flat plate (FP), and spheroid BAL designs. By modifying the O(2) boundary conditions, hepatocyte O(2) consumption levels, O(2) permeability of the ECM, and ECM void fractions, O(2) transport predictions are determined for each system as a function of time and distance. Accuracy of the predictive model is confirmed by comparing computational vs. experimental results for the HF BAL system. The model's results indicate that O(2) transport within all three BAL designs can be improved significantly by incorporating the enhancement technique. This technique modifies a diffusion-dominant gel ECM into a porous matrix with diffusive and convective flows that mutually transport O(2) through the ECMs. Although tortuous pathways increase the porous ECM's overall effective length of O(2) travel, the decreased transport resistances of these pathways allow O(2) to permeate more effectively into the ECMs. Furthermore, because the HF design employs convective flow on both its inner and outer ECM surfaces, greater control of O(2) transport through its ECM is predicted, as compared with the single O(2) source inputs of the flat plate and spheroid systems. The importance of this control is evaluated by showing how modifying the O(2) concentration and/or transfer coefficients of the

  20. Uptake of taurine, GABA, 5-HT, and dopamine by blood platelets in progressive myoclonus epilepsy.

    PubMed

    Airaksinen, E M

    1979-10-01

    The uptakes of four neurotransmitters (taurine, GABA, 5-HT, and dopamine) by blood platelets from patients with degenerative-type progressive myoclonus epilepsy (PME) and from controls were studied using different incubation times and different concentrations. Only the uptakes of taurine differed significantly between patients and controls: patients' uptakes were 70% to 80% of control values at 10, 30, 60, and 120 min of incubation time. Km values were approximately the same, but Vmax values in PME patients were lower, showing quantitative but not qualitative differences in taurine uptake by platelets in PME. These results suggest that a defect or an inhibitory mechanism of some factor needed in the transport or binding of taurine (but not of GABA, 5-HT, and dopamine) is present in PME.

  1. Taurine Biosynthesis by Neurons and Astrocytes*

    PubMed Central

    Vitvitsky, Victor; Garg, Sanjay K.; Banerjee, Ruma

    2011-01-01

    The physiological roles of taurine, a product of cysteine degradation and one of the most abundant amino acids in the body, remain elusive. Taurine deficiency leads to heart dysfunction, brain development abnormalities, retinal degradation, and other pathologies. The taurine synthetic pathway is proposed to be incomplete in astrocytes and neurons, and metabolic cooperation between these cell types is reportedly needed to complete the pathway. In this study, we analyzed taurine synthesis capability as reported by incorporation of radioactivity from [35S]cysteine into taurine, in primary murine astrocytes and neurons, and in several transformed cell lines (human (SH-SY5Y) and murine (N1E-115) neuroblastoma, human astrocytoma (U-87MG and 1321 N1), and rat glioma (C6)). Extensive incorporation of radioactivity from [35S]cysteine into taurine was observed in rat glioma cells as well as in primary mouse astrocytes and neurons, establishing the presence of an intact taurine synthesis pathway in these cells. Interestingly, exposure of cells to cysteine or cysteamine resulted in elevated intracellular hypotaurine without a corresponding increase in taurine levels, suggesting that oxidation of hypotaurine limits taurine synthesis in cells. Consistent with its role as an organic osmolyte, taurine synthesis was stimulated under hypertonic conditions in neurons. PMID:21778230

  2. Taurine biosynthesis by neurons and astrocytes.

    PubMed

    Vitvitsky, Victor; Garg, Sanjay K; Banerjee, Ruma

    2011-09-16

    The physiological roles of taurine, a product of cysteine degradation and one of the most abundant amino acids in the body, remain elusive. Taurine deficiency leads to heart dysfunction, brain development abnormalities, retinal degradation, and other pathologies. The taurine synthetic pathway is proposed to be incomplete in astrocytes and neurons, and metabolic cooperation between these cell types is reportedly needed to complete the pathway. In this study, we analyzed taurine synthesis capability as reported by incorporation of radioactivity from [(35)S]cysteine into taurine, in primary murine astrocytes and neurons, and in several transformed cell lines (human (SH-SY5Y) and murine (N1E-115) neuroblastoma, human astrocytoma (U-87 MG and 1321 N1), and rat glioma (C6)). Extensive incorporation of radioactivity from [(35)S]cysteine into taurine was observed in rat glioma cells as well as in primary mouse astrocytes and neurons, establishing the presence of an intact taurine synthesis pathway in these cells. Interestingly, exposure of cells to cysteine or cysteamine resulted in elevated intracellular hypotaurine without a corresponding increase in taurine levels, suggesting that oxidation of hypotaurine limits taurine synthesis in cells. Consistent with its role as an organic osmolyte, taurine synthesis was stimulated under hypertonic conditions in neurons.

  3. [Taurine and its potential therapeutic application].

    PubMed

    Szymański, Konrad; Winiarska, Katarzyna

    2008-02-25

    Taurine (2-aminoethylsulphonic acid), a non-protein amino acid, is present in most animal tissues. Its highest concentrations are found in skeletal muscles, heart, brain, and retina. Although this compound can be synthesized from other sulfonic amino acids such as methionine and cysteine, the endogenous production is insufficient for the human organism, so taurine has to be delivered with food. Animal products such as fish, meat, and milk are good sources of taurine. Taurine exhibits antioxidative properties, regulates intracellular Ca2+ concentration, acts as a neuromediator and neuromodulator, is responsible for osmoregulation, is involved in cholic acid production, and modulates inflammatory reactions. The amino acid seems to be an important trophic factor in the retina, nervous system, and kidneys. The protective action of taurine on heart muscle and the antagonistic effects of this amino acid and angiotensin II arouse great interest. The role of taurine in glucose metabolism regulation is also extensively studied. However, the detailed mechanisms of taurine's action are still unknown. Lowered tissue taurine concentrations are characteristic of many pathological states, including diabetes. In many studies, also in clinical trials, it has been reported that supplementation with taurine reverses or at least attenuates pathological changes. Therefore, it seems likely that taurine might be used in the treatment of cardiomyopathy, myotony, hypercholesterolemia, or diabetes. However, future thorough studies are required.

  4. Substantia nigra osmoregulation: taurine and ATP involvement.

    PubMed

    Morales, Ingrid; Dopico, Jose G; Sabate, Magdalena; Gonzalez-Hernandez, Tomas; Rodriguez, Manuel

    2007-05-01

    An extracellular nonsynaptic taurine pool of glial origin was recently reported in the substantia nigra (SN). There is previous evidence showing taurine as an inhibitory neurotransmitter in the SN, but the physiological role of this nonsynaptic pool of taurine has not been explored. By using microdialysis methods, we studied the action of local osmolarity on the nonsynaptic taurine pool in the SN of the rat. Hypoosmolar pulses (285-80 mosM) administered in the SN by the microdialysis probe increased extrasynaptic taurine in a dose-dependent way, a response that was counteracted by compensating osmolarity with choline. The opposite effect (taurine decrease) was observed when osmolarity was increased. Under basal conditions, the blockade of either the AMPA-kainate glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dionine disodium or the purinergic receptors with pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid modified the taurine concentration, suggesting that both receptors modulate the extrasynaptic pool of taurine. In addition, these drugs decreased the taurine response to hypoosmolar pulses, suggesting roles for glutamatergic and purinergic receptors in the taurine response to osmolarity. The participation of purinergic receptors was also supported by the fact that ATP (which, under basal conditions, increased the extrasynaptic taurine in a dose-dependent way) administered in doses saturating purinergic receptors also decreased the taurine response to hypoosmolarity. Taken together, present data suggest osmoregulation as a role of the nonsynaptic taurine pool of the SN, a function that also involves glutamate and ATP and that could influence the nigral cell vulnerability in Parkinson's disease.

  5. Effect of taurine depletion on excitation-contraction coupling and Cl- conductance of rat skeletal muscle.

    PubMed

    De Luca, A; Pierno, S; Camerino, D C

    1996-01-25

    The pharmacological action of taurine on skeletal muscle is to stabilize sarcolemma by increasing macroscopic conductance to Cl- (GCl), whereas a proposed physiological role for the amino acid is to modulate excitation-contraction coupling mechanism via Ca2+ availability. To get insight in the physiological role of taurine in skeletal muscle, the effects of its depletion were evaluated on voltage threshold for mechanical activation and GCl with the two intracellular microelectrode method in 'point' voltage clamp mode and current clamp mode, respectively. The experiments were performed on extensor digitorum longus muscle fibers from rats depleted of taurine by a chronic 4 week treatment with guanidinoethane sulfonate, a known inhibitor of taurine transporter. The treatment significantly modified the mechanical threshold of striated fibers; i.e. at each pulse duration they needed significantly less depolarization to contract and the fitted rheobase voltage was more negative by 10 mV with respect to untreated muscle fibers. In parallel, the treatment with guanidinoethane sulfonate produced a significant 40% lowering of GCl. In vitro application of 60 mM of taurine to such depleted muscles almost completely restored the mechanical threshold and increased GCl even above the value of untreated control. However, in vitro application of 60 mM of either taurine or guanidinoethane sulfonate to untreated control muscles did not cause any change of the mechanical threshold but increased GCl by 40% and 21%, respectively. Furthermore, 100 microM of the S-(-) enantiomer of 2-(p-chlorophenoxy)propionic acid almost fully blocked GCl but did not produce any change in the mechanical threshold of normal muscle fibers. The present results show that the large amount of intracellular taurine plays a role in the excitation-contraction coupling mechanism of striated muscle fibers. This action is independent from any effect involving muscle Cl- channels, but it is likely mediated by the

  6. The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis.

    PubMed

    Cherrington, Nathan J; Estrada, Teresa E; Frisk, Harrison A; Canet, Mark J; Hardwick, Rhiannon N; Dvorak, Bohuslav; Lux, Katie; Halpern, Melissa D

    2013-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants and is characterized by an extensive hemorrhagic inflammatory necrosis of the distal ileum and proximal colon. We have previously shown that, during the development of experimental NEC, the liver plays an important role in regulating inflammation in the ileum, and accumulation of ileal bile acids (BA) along with dysregulation of ileal BA transporters contributes to ileal damage. Given these findings, we speculated that hepatic BA transporters would also be altered in experimental NEC. Using both rat and mouse models of NEC, levels of Cyp7a1, Cyp27a1, and the hepatic BA transporters Bsep, Ntcp, Oatp2, Oatp4, Mrp2, and Mrp3 were investigated. In addition, levels of hepatic BA transporters were also determined when the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-18, which are both elevated in NEC, are neutralized during disease development. Ntcp and Mrp2 were decreased in NEC, but elevated ileal BA levels were not responsible for these reductions. However, neutralization of TNF-α normalized Ntcp, whereas removal of IL-18 normalized Mrp2 levels. These data show that the hepatic transporters Ntcp and Mrp2 are downregulated, whereas Cyp27a1 is increased in rodent models of NEC. Furthermore, increased levels of TNF-α and IL-18 in experimental NEC may play a role in the regulation of Ntcp and Mrp2, respectively. These data suggest the gut-liver axis should be considered when therapeutic modalities for NEC are developed.

  7. Clinical CYP3A inhibitor alternatives to ketoconazole, clarithromycin and itraconazole, are not transported into the liver by hepatic organic anion transporting polypeptides and organic cation transporter 1.

    PubMed

    Higgins, J William; Ke, Alice B; Zamek-Gliszczynski, Maciej J

    2014-11-01

    Ketoconazole is no longer available for clinical determination of worst-case victim drug-drug interaction (DDI) potential for cytochrome P450 3A (CYP3A)-substrate drugs; clarithromycin and itraconazole are the proposed replacements. Ketoconazole DDIs are described by unbound systemic exposures due to absence of carrier-facilitated hepatic uptake, but this aspect of clarithromycin and itraconazole disposition has not been investigated. At present, transport of clarithromycin, itraconazole, and hydroxyitraconazole by hepatic organic anion transporting polypeptides (OATPs) and organic cation transporter 1 (OCT1) was examined in vitro and in vivo. As for ketoconazole, uptake of clarithromycin, itraconazole, and hydroxyitraconazole into OATP1B1, OATP1B3, OATP2B1, and OCT1 expressing human embryonic kidney 293 (HEK293) cells was not greater than in vector controls. Uptake into these HEK293 cells and human hepatocytes was not impaired by the prototypical OATP, OCT, and sodium/taurocholate cotransporting polypeptide inhibitors bromosulfophthalein, imipramine, and taurocholate, respectively. In contrast, uptake of the positive controls, atorvastatin for OATPs and metformin for OCT1, was significantly enhanced by relevant transporter expression, and uptake into both these HEK293 cells and human hepatocytes was significantly impaired by prototypical inhibitors. In Oatp1a/1b gene cluster knockout mice, which lack the major hepatic Oatps, and in Oct1/2 knockout mice, ketoconazole, clarithromycin, itraconazole, and hydroxyitraconazole oral exposure was not increased, and the liver-to-blood partition coefficient (Kp) was not decreased. By contrast relative to wild-type mice, in Oatp1a/1b- and Oct1/2-knockout mice, atorvastatin and metformin oral exposure was significantly increased, and liver Kp was significantly decreased. The present studies provide in vitro and in vivo evidence that, like ketoconazole, clarithromycin, itraconazole, and hydroxyitraconazole are not transported

  8. Hepatic and renal Bcrp transporter expression in mice treated with perfluorooctanoic acid

    PubMed Central

    Eldasher, Lobna M.; Wen, Xia; Little, Michael S.; Bircsak, Kristin M.; Yacovino, Lindsay L.; Aleksunes, Lauren M.

    2013-01-01

    The breast cancer resistance protein (Bcrp) is an efflux transporter that participates in the biliary and renal excretion of drugs and environmental chemicals. Recent evidence suggests that pharmacological activation of the peroxisome proliferator activated receptor alpha (PPARα) can up-regulate the hepatic expression of Bcrp. The current study investigated the regulation of hepatic and renal Bcrp mRNA and protein in mice treated with the PPARα agonist perfluorooctanoic acid (PFOA) and the ability of PFOA to alter human BCRP function in vitro. Bcrp mRNA and protein expression were quantified in the livers and kidneys of male C57BL/6 mice treated with vehicle or PFOA (1 or 3 mg/kg/day oral gavage) for 7 days. PFOA treatment increased liver weights as well as the hepatic mRNA and protein expression of the PPARα target gene, cytochrome P450 4a14. Compared to vehicle-treated control mice, PFOA increased hepatic Bcrp mRNA and protein between 1.5- and 3-fold. Immunofluorescent staining confirmed enhanced canalicular Bcrp staining in liver sections from PFOA-treated mice. The kidney expression of cytochrome P450 4a14 mRNA, but not Bcrp, was increased in mice treated with PFOA. Micromolar concentrations of PFOA decreased human BCRP ATPase activity and inhibited BCRP-mediated transport in inverted membrane vesicles. Together, these studies demonstrate that PFOA induces hepatic Bcrp expression in mice and may inhibit human BCRP transporter function at concentrations that exceed levels observed in humans. PMID:23435180

  9. Regulation of hepatic ABCC transporters by xenobiotics and in disease states

    PubMed Central

    Gu, Xinsheng; Manautou, Jose E.

    2015-01-01

    The subfamily of ABCC transporters consists of 13 members in mammals, including the multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and the cystic fibrosis transmembrane conductance regulator (CFTR). These proteins play roles in chemical detoxification, disposition, and normal cell physiology. ABCC transporters are expressed differentially in the liver and are regulated at the transcription and translation level. Their expression and function are also controlled by post-translational modification and membrane-trafficking events. These processes are tightly regulated. Information about alterations in the expression of hepatobiliary ABCC transporters could provide important insights into the pathogenesis of diseases and disposition of xenobiotics. In this review, we describe the regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporters, and cell-signaling molecules. PMID:20233023

  10. Insulin-like Effects of Taurine,

    DTIC Science & Technology

    1978-03-17

    A one-time injection of taurine in a dose of 200 mg/kg will increase insulin-like activity in rat plasma, doubles the glycogen content of the liver...and decreases glycemia. In in vitro experiments taurine increases glucose absorption by isolated diaphragms and raises insulin activity. On the basis...of increased adenylacyclase activity in incubated diaphragms upon introduction of taurine and insulin-like action of 3’, 5, -AMF and theophylline the

  11. Maternal taurine supplementation attenuates maternal fructose-induced metabolic and inflammatory dysregulation and partially reverses adverse metabolic programming in offspring.

    PubMed

    Li, M; Reynolds, C M; Sloboda, D M; Gray, C; Vickers, M H

    2015-03-01

    Excessive fructose consumption is associated with insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), and high fructose intake during pregnancy can lead to compromised fetal development in the rat. Evidence suggests that the amino acid taurine can ameliorate fructose-induced IR and NAFLD in nonpregnant animals. This study investigated the efficacy of taurine supplementation on maternal fructose-induced metabolic dysfunction and neonatal health. Time-mated Wistar rats were randomized to four groups during pregnancy and lactation: (a) control diet (CON), (b) CON supplemented with 1.5% taurine in drinking water (CT), (c) CON supplemented with fructose solution (F) and (d) F supplemented with taurine (FT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analyzed. Maternal hyperinsulinemia, increased homeostasis model assessment of IR indices and elevated proinflammatory cytokines were observed in F group and normalized in FT group. Maternal fructose-induced hepatic steatosis accompanied with increased liver weight was ameliorated with taurine supplementation. Maternal hepatic sterol regulatory element-binding protein-1c and fatty acid synthase expression was significantly increased in the F group compared to the CON, CT and FT groups. Neonatal hepatic phosphoenolpyruvate carboxykinase expression was increased in male F neonates compared to the CON, CT and FT groups and was increased in female F and FT neonates compared to CON and CT. Interleukin-1β expression was decreased in male CT and FT neonates compared to other male groups. Hepatic tumour necrosis factor receptor-1 was lower in the male FT group than the F group. These results demonstrate that maternal taurine supplementation can partially reverse fructose-induced maternal metabolic dysfunction and may ameliorate adverse developmental programming effects in offspring in a sex-specific manner. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Impact of taurine depletion on glucose control and insulin secretion in mice.

    PubMed

    Ito, Takashi; Yoshikawa, Natsumi; Ito, Hiromi; Schaffer, Stephen W

    2015-09-01

    Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. The potential protective effects of taurine on coronary heart disease2

    PubMed Central

    Wójcik, Oktawia P.; Koenig, Karen L.; Zeleniuch-Jacquotte, Anne; Costa, Max; Chen, Yu

    2009-01-01

    In humans, taurine (2-aminoethanesulfonic acid) is mainly obtained from diet. Despite the fact that the health effects of taurine are largely unknown, taurine has become a popular supplement and ingredient in energy drinks in recent years. Evidence from mechanistic and animal studies has shown that the main biological actions of taurine include its ability to conjugate bile acids, regulate blood pressure (BP), and act as a potent antioxidant and anti-inflammatory agent. These actions suggest that high levels of taurine may be protective against coronary heart disease (CHD). However, data from epidemiologic and intervention studies in humans are limited. We review what is known about taurine’s metabolism, its transportation in the body, its food sources, and evidence of its effect on cardiovascular health from in vitro, animal, and epidemiologic studies. We also discuss shortcomings of the human studies that need to be addressed in the future. The identification of taurine as a preventive factor for CHD may be of great public health importance. PMID:19592001

  14. Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance.

    PubMed

    Elshorbagy, Amany K; Valdivia-Garcia, Maria; Mattocks, Dwight A L; Plummer, Jason D; Orentreich, David S; Orentreich, Norman; Refsum, Helga; Perrone, Carmen E

    2013-04-01

    Methionine-restricted (MR) rats, which are lean and insulin sensitive, have low serum total cysteine (tCys) and taurine and decreased hepatic expression and activity indices of stearoyl-coenzyme A desaturase-1 (SCD1). These effects are partly or completely reversed by cysteine supplementation. We investigated whether reversal of MR phenotypes can be achieved by other sulfur compounds, namely taurine or N-acetylcysteine (NAC). MR and control-fed (CF) rats were supplemented with taurine (0.5%) or NAC (0.5%) for 12weeks. Adiposity, serum sulfur amino acids (SAA), Scd1 gene expression in liver and white adipose tissue, and SCD1 activity indices (calculated from serum fatty acid profile) were monitored. Taurine supplementation of MR rats did not restore weight gain or hepatic Scd1 expression or indices to CF levels, but further decreased adiposity. Taurine supplementation of CF rats did not affect adiposity, but lowered triglyceridemia. NAC supplementation in MR rats raised tCys and partly or completely reversed MR effects on weight, fat %, Scd1 expression in liver and white adipose tissue, and estimated SCD1 activity. In CF rats, NAC decreased body fat % and lowered SCD1-18 activity index (P<0.001). Serum triglycerides and leptin were over 40% lower in CF+NAC relative to CF rats (P≤0.003 for both). In all groups, change in tCys correlated with change in SCD1-16 index (partial r=0.60, P<0.001) independent of other SAA. The results rule out taurine as a mediator of increased adiposity produced by cysteine in MR, and show that NAC, similar to L-cysteine, blocks anti-obesity effects of MR. Our data show that dietary SAA can influence adiposity in part through mechanisms that converge on SCD1 function. This may have implications for understanding and preventing human obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Computer Modeling of Yttrium-90-Microsphere Transport in the Hepatic Arterial Tree to Improve Clinical Outcomes

    SciTech Connect

    Kennedy, Andrew S.; Kleinstreuer, Clement; Basciano, Christopher A.; Dezarn, William A.

    2010-02-01

    Purpose: Radioembolization (RE) via yttrium-90 ({sup 90}Y) microspheres is an effective and safe treatment for unresectable liver malignancies. However, no data are available regarding the impact of local blood flow dynamics on {sup 90}Y-microsphere transport and distribution in the human hepatic arterial system. Methods and Materials: A three-dimensional (3-D) computer model was developed to analyze and simulate blood-microsphere flow dynamics in the hepatic arterial system with tumor. Supplemental geometric and flow data sets from patients undergoing RE were also available to validate the accuracy of the computer simulation model. Specifically, vessel diameters, curvatures, and branching patterns, as well as blood flow velocities/pressures and microsphere characteristics (i.e., diameter and specific gravity), were measured. Three-dimensional computer-aided design software was used to create the vessel geometries. Initial trials, with 10,000 noninteracting microspheres released into the hepatic artery, used resin spheres 32-{mu}m in diameter with a density twice that of blood. Results: Simulations of blood flow subject to different branch-outlet pressures as well as blood-microsphere transport were successfully carried out, allowing testing of two types of microsphere release distributions in the inlet plane of the main hepatic artery. If the inlet distribution of microspheres was uniform (evenly spaced particles), a greater percentage would exit into the vessel branch feeding the tumor. Conversely, a parabolic inlet distribution of microspheres (more particles around the vessel center) showed a high percentage of microspheres exiting the branch vessel leading to the normal liver. Conclusions: Computer simulations of both blood flow patterns and microsphere dynamics have the potential to provide valuable insight on how to optimize {sup 90}Y-microsphere implantation into hepatic tumors while sparing normal tissue.

  16. N-acetyltaurine dissimilated via taurine by Delftia acidovorans NAT.

    PubMed

    Mayer, Jutta; Denger, Karin; Smits, Theo H M; Hollemeyer, Klaus; Groth, Ulrich; Cook, Alasdair M

    2006-07-01

    The naturally occurring sulfonate N-acetyltaurine was synthesized chemically and its identity was confirmed. Aerobic enrichment cultures for bacteria able to utilize N-acetyltaurine as sole source of fixed nitrogen or as sole source of carbon were successful. One representative isolate, strain NAT, which was identified as a strain of Delftia acidovorans, grew with N-acetyltaurine as carbon source and excreted stoichiometric amounts of sulfate and ammonium. Inducible enzyme activities were measured in crude extracts of this organism to elucidate the degradative pathway. Cleavage of N-acetyltaurine by a highly active amidase yielded acetate and taurine. The latter was oxidatively deaminated by taurine dehydrogenase to ammonium and sulfoacetaldehyde. This key intermediate of sulfonate catabolism was desulfonated by the known reaction of sulfoacetaldehyde acetyltransferase to sulfite and acetyl phosphate, which was further degraded to enter central metabolism. A degradative pathway including transport functions is proposed.

  17. Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy.

    PubMed

    Terrill, Jessica R; Duong, Marisa N; Turner, Rufus; Le Guiner, Caroline; Boyatzis, Amber; Kettle, Anthony J; Grounds, Miranda D; Arthur, Peter G

    2016-10-01

    Duchenne Muscular Dystrophy (DMD) is a fatal skeletal muscle wasting disease presenting with excessive myofibre necrosis and increased inflammation and oxidative stress. In the mdx mouse model of DMD, homeostasis of the amino acid taurine is altered, and taurine administration drastically decreases muscle necrosis, dystropathology, inflammation and protein thiol oxidation. Since the severe pathology of the Golden Retriever Muscular Dystrophy (GRMD) dog model more closely resembles the human DMD condition, we aimed to assess the generation of oxidants by inflammatory cells and taurine metabolism in this species. In muscles of 8 month GRMD dogs there was an increase in the content of neutrophils and macrophages, and an associated increase in elevated myeloperoxidase, a protein secreted by neutrophils that catalyses production of the highly reactive hypochlorous acid (HOCl). There was also increased chlorination of tyrosines, a marker of HOCl generation, increased thiol oxidation of many proteins and irreversible oxidative protein damage. Taurine, which functions as an antioxidant by trapping HOCl, was reduced in GRMD plasma; however taurine was increased in GRMD muscle tissue, potentially due to increased muscle taurine transport and synthesis. These data indicate a role for HOCl generated by neutrophils in the severe dystropathology of GRMD dogs, which may be exacerbated by decreased availability of taurine in the blood. These novel data support continued research into the precise roles of oxidative stress and taurine in DMD and emphasise the value of the GRMD dogs as a suitable pre-clinical model for testing taurine as a therapeutic intervention for DMD boys.

  18. Altered Regulation of Hepatic Efflux Transporters Disrupts Acetaminophen Disposition in Pediatric Nonalcoholic Steatohepatitis

    PubMed Central

    Canet, Mark J.; Merrell, Matthew D.; Hardwick, Rhiannon N.; Bataille, Amy M.; Campion, Sarah N.; Ferreira, Daniel W.; Xanthakos, Stavra A.; Manautou, Jose E.; Hesham A-Kader, H.; Erickson, Robert P.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, representing a spectrum of liver pathologies that include simple hepatic steatosis and the more advanced nonalcoholic steatohepatitis (NASH). The current study was conducted to determine whether pediatric NASH also results in altered disposition of acetaminophen (APAP) and its two primary metabolites, APAP-sulfate and APAP-glucuronide. Pediatric patients with hepatic steatosis (n = 9) or NASH (n = 3) and healthy patients (n = 12) were recruited in a small pilot study design. All patients received a single 1000-mg dose of APAP. Blood and urine samples were collected at 1, 2, and 4 hours postdose, and APAP and APAP metabolites were determined by high-performance liquid chromatography. Moreover, human liver tissues from patients diagnosed with various stages of NAFLD were acquired from the Liver Tissue Cell Distribution System to investigate the regulation of the membrane transporters, multidrug resistance–associated protein 2 and 3 (MRP2 and MRP3, respectively). Patients with the more severe disease (i.e., NASH) had increased serum and urinary levels of APAP-glucuronide along with decreased serum levels of APAP-sulfate. Moreover, an induction of hepatic MRP3 and altered canalicular localization of the biliary efflux transporter, MRP2, describes the likely mechanism for the observed increase in plasma retention of APAP-glucuronide, whereas altered regulation of sulfur activation genes may explain decreased sulfonation activity in NASH. APAP-glucuronide and APAP-sulfate disposition is altered in NASH and is likely due to hepatic membrane transporter dysregulation as well as altered intracellular sulfur activation. PMID:25788542

  19. Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis.

    PubMed

    Canet, Mark J; Merrell, Matthew D; Hardwick, Rhiannon N; Bataille, Amy M; Campion, Sarah N; Ferreira, Daniel W; Xanthakos, Stavra A; Manautou, Jose E; A-Kader, H Hesham; Erickson, Robert P; Cherrington, Nathan J

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, representing a spectrum of liver pathologies that include simple hepatic steatosis and the more advanced nonalcoholic steatohepatitis (NASH). The current study was conducted to determine whether pediatric NASH also results in altered disposition of acetaminophen (APAP) and its two primary metabolites, APAP-sulfate and APAP-glucuronide. Pediatric patients with hepatic steatosis (n = 9) or NASH (n = 3) and healthy patients (n = 12) were recruited in a small pilot study design. All patients received a single 1000-mg dose of APAP. Blood and urine samples were collected at 1, 2, and 4 hours postdose, and APAP and APAP metabolites were determined by high-performance liquid chromatography. Moreover, human liver tissues from patients diagnosed with various stages of NAFLD were acquired from the Liver Tissue Cell Distribution System to investigate the regulation of the membrane transporters, multidrug resistance-associated protein 2 and 3 (MRP2 and MRP3, respectively). Patients with the more severe disease (i.e., NASH) had increased serum and urinary levels of APAP-glucuronide along with decreased serum levels of APAP-sulfate. Moreover, an induction of hepatic MRP3 and altered canalicular localization of the biliary efflux transporter, MRP2, describes the likely mechanism for the observed increase in plasma retention of APAP-glucuronide, whereas altered regulation of sulfur activation genes may explain decreased sulfonation activity in NASH. APAP-glucuronide and APAP-sulfate disposition is altered in NASH and is likely due to hepatic membrane transporter dysregulation as well as altered intracellular sulfur activation. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Manganese exposure inhibits the clearance of extracellular GABA and influences taurine homeostasis in the striatum of developing rats

    PubMed Central

    Fordahl, Steve C.; Anderson, Joel G.; Cooney, Paula T.; Weaver, Tara L.; Colyer, Christa L.; Erikson, Keith M.

    2010-01-01

    Manganese (Mn) accumulation in the brain has been shown to alter the neurochemistry of the basal ganglia. Mn-induced alterations in dopamine biology are fairly well understood, but recently more evidence has emerged characterizing the role of γ-aminobutyric acid (GABA) in this dysfunction. The purpose of this study was to determine if the previously observed Mn-induced increase in extracellular GABA (GABAEC) was due to altered GABA transporter (GAT) function, and whether Mn perturbs other amino acid neurotransmitters, namely taurine and glycine (known modulators of GABA). Extracellular GABA, taurine, and glycine concentrations were collected from the striatum of control (CN) or Mn-exposed Sprague-Dawley rats using in vivo microdialysis, and the GAT inhibitor nipecotic acid (NA) was used to probe GAT function. Tissue and extracellular Mn levels were significantly increased, and the Fe:Mn ratio was decreased 36-fold in the extracellular space due to Mn exposure. NA led to a 2-fold increase in GABAEC of CNs, a response that was attenuated by Mn. Taurine responded inversely to GABA, and a novel 10-fold increase in taurine was observed after the removal of NA in CNs. Mn blunted this response and nearly abolished extracellular taurine throughout collection. Striatal taurine transporter (Slc6a6) mRNA levels were significantly increased with Mn exposure, and Mn significantly increased 3H-Taurine uptake after 3-minute exposure in primary rat astrocytes. These data suggest that Mn increases GABAEC by inhibiting the function of GAT, and that perturbed taurine homeostasis potentially impacts neural function by jeopardizing the osmoregulatory and neuromodulatory functions of taurine in the brain. PMID:20832424

  1. Manganese exposure inhibits the clearance of extracellular GABA and influences taurine homeostasis in the striatum of developing rats.

    PubMed

    Fordahl, Steve C; Anderson, Joel G; Cooney, Paula T; Weaver, Tara L; Colyer, Christa L; Erikson, Keith M

    2010-12-01

    Manganese (Mn) accumulation in the brain has been shown to alter the neurochemistry of the basal ganglia. Mn-induced alterations in dopamine biology are fairly well understood, but recently more evidence has emerged characterizing the role of γ-aminobutyric acid (GABA) in this dysfunction. The purpose of this study was to determine if the previously observed Mn-induced increase in extracellular GABA (GABA(EC)) was due to altered GABA transporter (GAT) function, and whether Mn perturbs other amino acid neurotransmitters, namely taurine and glycine (known modulators of GABA). Extracellular GABA, taurine, and glycine concentrations were collected from the striatum of control (CN) or Mn-exposed Sprague-Dawley rats using in vivo microdialysis, and the GAT inhibitor nipecotic acid (NA) was used to probe GAT function. Tissue and extracellular Mn levels were significantly increased, and the Fe:Mn ratio was decreased 36-fold in the extracellular space due to Mn-exposure. NA led to a 2-fold increase in GABA(EC) of CNs, a response that was attenuated by Mn. Taurine responded inversely to GABA, and a novel 10-fold increase in taurine was observed after the removal of NA in CNs. Mn blunted this response and nearly abolished extracellular taurine throughout collection. Striatal taurine transporter (Slc6a6) mRNA levels were significantly increased with Mn-exposure, and Mn significantly increased (3)H-Taurine uptake after 3-min exposure in primary rat astrocytes. These data suggest that Mn increases GABA(EC) by inhibiting the function of GAT, and that perturbed taurine homeostasis potentially impacts neural function by jeopardizing the osmoregulatory and neuromodulatory functions of taurine in the brain.

  2. Regulation of hepatic drug transporter activity and expression by organochlorine pesticides.

    PubMed

    Bucher, Simon; Le Vee, Marc; Jouan, Elodie; Fardel, Olivier

    2014-03-01

    Organochlorine (OC) pesticides constitute a major class of persistent and toxic organic pollutants, known to modulate drug-detoxifying enzymes. In the present study, OCs were demonstrated to also alter the activity and expression of human hepatic drug transporters. Activity of the sinusoidal influx transporter OCT1 (organic cation transporter 1) was thus inhibited by endosulfan, chlordane, heptachlor, lindane, and dieldrine, but not by dichlorodiphenyltrichloroethane isomers, whereas those of the canalicular efflux pumps MRP2 (multidrug resistance-associated protein 2) and BCRP (breast cancer resistance protein) were blocked by endosulfan, chlordane, heptachlor, and chlordecone; this latter OC additionally inhibited the multidrug resistance gene 1 (MDR1)/P-glycoprotein (P-gp) activity. OCs, except endosulfan, were next found to induce MDR1/P-gp and MRP2 mRNA expressions in hepatoma HepaRG cells; some of them also upregulated BCRP. By contrast, expression of sinusoidal transporters was not impaired (organic anion-transporting polypeptide (OATP) 1B1 and OATP2B1) or was downregulated (sodium taurocholate co-transporting polypeptide (NTCP) and OCT1). Such regulations of drug transporter activity and expression, depending on the respective nature of OCs and transporters, may contribute to the toxicity of OC pesticides.

  3. Hepatitis

    MedlinePlus

    ... low because of routine testing of donated blood. Sexual transmission and transmission among family members through close contact ... associated with drinking contaminated water. Hepatitis Viruses ... B Blood, needles, sexual 10% of older children develop chronic infection. 90% ...

  4. Novel protective role of curcumin and taurine combination against experimental hepatocarcinogenesis

    PubMed Central

    El-Houseini, Motawa Eisa; El-Agoza, Ibrahim Ali; Sakr, Mona Mohamed; El-Malky, Ghada Mohamed

    2017-01-01

    Hepatocarcinogenesis is a prerequisite to hepatocellular carcinoma (HCC), which is one of the most common cancers among humans. Therefore, it is important to search for agents that protect against hepatocarcinogenesis. The present study aimed to investigate the protective effects of a combination of taurine and curcumin against experimental hepatocarcinogenesis induced by diethyl nitrosamine (DENA) in a rat model. A total of 100 rats were divided into eight groups. Eight weeks following DENA injection and treatment with curcumin and taurine, the rats were sacrificed to obtain blood and hepatic tissue samples for the evaluation of various markers and histopathological observations. Serum levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), α-fetoprotein (AFP) and α-L-fucosidase (AFU) were determined. Rats injected with DENA for eight weeks showed a high percentage of malignant changes in hepatic tissues, as well as a significant increases in the serum levels of AFP and AFU and significant reductions in the serum levels of IL-2 and IFN-γ. Treatment with curcumin and taurine markedly reduced the extent of malignant changes in the rat liver tissues, with their liver tissues showing patterns similar to that of the normal control rats. In addition, this combination resulted in normal serum levels of IL-2, IFN-γ, AFP and AFU. The results of the present study suggested that a combination of curcumin and taurine may be a novel prophylactic agent against hepatocarcinogenesis in high-risk groups exposed to chemical hepatocarcinogens. PMID:28123463

  5. Prophylactic and therapeutic effects of taurine against aluminum-induced acute hepatotoxicity in mice.

    PubMed

    El-Sayed, Wael M; Al-Kahtani, Mohamed A; Abdel-Moneim, Ashraf M

    2011-08-30

    Aluminum is a well known neurotoxin and a possible candidate of hepatotoxins to humans. Using natural antioxidants against metal-induced hepatotoxicity is a modern approach. In the present study, Aluminum (AlCl(3)) intoxication (a single injection of 25mg Al(3+)/kg, i.p.) for 24h in mice resulted in elevations in serum alanine aminotransferase activity and serum tumor necrosis factor and hepatic malondialdehyde levels. Aluminum reduced the activities of glutathione peroxidase, glutathione S-transferase, quinone oxidoreductase, and catalase in liver. In addition, Al caused hepatic hemorrhage, cellular degeneration as well as necrosis of hepatocytes. Ultrastructure examination showed swelling of mitochondria, derangement of rough endoplasmic reticulum cisternae and pleomorphic nuclei with abnormal chromatin distribution. Taurine, a sulfur-containing amino acid was administered to mice daily for 5 days before (at 100mg/kg, i.p.) or 2h after (a single dose of 1g/kg, i.p.) aluminum administration. Treating mice with taurine at either dosing regimens, pre- or post-aluminum administration alleviated aluminum oxidative damaging effects. The rate of recovery was better when taurine was administered prior to Al. Taurine had anaphylactic and therapeutic activity against hepatotoxicity induced by aluminum in mice.

  6. Dietary taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in streptozotocin-induced Sprague-Dawley rats.

    PubMed

    Yu, Xiaoping; Xu, Zhaoxia; Mi, Mantian; Xu, Hongxia; Zhu, Jundong; Wei, Na; Chen, Ka; Zhang, Qianyong; Zeng, Kaihong; Wang, Jian; Chen, Fang; Tang, Yong

    2008-03-01

    The purpose of this study was to investigate whether taurine ameliorate the diabetic retinopathy, and to further explore the underlying mechanisms. The Sprague-Dawley rats were injected with streptozotocin to establish experimental diabetic model, then fed without or with 1.2% taurine for additional 4-12 weeks. After that, the protective effects of dietary taurine supplementation on diabetic retinopathy were estimated. Our results showed that chronic taurine supplement effectively improved diabetic retinopathy as changes of histopathology and ultrastructure. The supplementation could not lower plasma glucose concentration (P > 0.05), but caused an elevation in taurine content and a decline in levels of glutamate and gamma-aminobutyric acid (GABA) in diabetic retina (P < 0.05). Moreover, chronic taurine supplementation increased glutamate transporter (GLAST) expression (P < 0.05), decreased intermediate filament glial fibrillary acidic protein (GFAP) and N-methyl-D: -aspartate receptor subunit 1 (NR1) expression in diabetic retina (P < 0.05). These results demonstrated that chronic taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in rats.

  7. Taurine release in the rat vas deferens is modulated by Ca2+ and is independent of contractions.

    PubMed

    Diniz, C; da Cruz Fresco, P; Gonçalves, J

    1999-07-09

    Electrical field stimulation induces taurine release in rat vas deferens. In the present study, it was investigated if this release is secondary to contraction. The influence of Ca2+ and of the stimulation conditions was also studied. Contractions evoked by electrical field stimulation (5 Hz/270 pulses, transverse or longitudinal) were recorded and released taurine was quantified by high performance liquid chromatography with fluorimetric detection. Ca2+ removal abolished contractions, but not the overflow of taurine. Overflow elicited by longitudinal electrical field stimulation was higher than that elicited by transverse electrical field stimulation. Increasing the current strength also increased taurine overflow. In Ca2+-free medium, taurine overflow was decreased by caffeine (5 mM) or ryanodine (10 microM) but increased by dantrolene (50 microM). The results indicate that taurine release evoked by electrical field stimulation is (i) independent of contraction, (ii) modulated by Ca2+, (iii) potential dependent, and may be due to a decrease in taurine affinity for the plasma membrane and/or to an increase of Na+-dependent outward transport.

  8. Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide

    PubMed Central

    Mao, Fengfeng; Jing, Zhiyi; Li, Yunfei; Liu, Yang; Peng, Bo; Yan, Huan; Qi, Yonghe; Sun, Yinyan; Guo, Ju-Tao; Sui, Jianhua; Wang, Fengchao; Li, Wenhui

    2015-01-01

    Hepatitis D virus (HDV) is the smallest virus known to infect human. About 15 million people worldwide are infected by HDV among those 240 million infected by its helper hepatitis B virus (HBV). Viral hepatitis D is considered as one of the most severe forms of human viral hepatitis. No specific antivirals are currently available to treat HDV infection and antivirals against HBV do not ameliorate hepatitis D. Liver sodium taurocholate co-transporting polypeptide (NTCP) was recently identified as a common entry receptor for HDV and HBV in cell cultures. Here we show HDV can infect mice expressing human NTCP (hNTCP-Tg). Antibodies against critical regions of HBV envelope proteins blocked HDV infection in the hNTCP-Tg mice. The infection was acute yet HDV genome replication occurred efficiently, evident by the presence of antigenome RNA and edited RNA species specifying large delta antigen in the livers of infected mice. The resolution of HDV infection appears not dependent on adaptive immune response, but might be facilitated by innate immunity. Liver RNA-seq analyses of HDV infected hNTCP-Tg and type I interferon receptor 1 (IFNα/βR1) null hNTCP-Tg mice indicated that in addition to induction of type I IFN response, HDV infection was also associated with up-regulation of novel cellular genes that may modulate HDV infection. Our work has thus proved the concept that NTCP is a functional receptor for HDV infection in vivo and established a convenient small animal model for investigation of HDV pathogenesis and evaluation of antiviral therapeutics against the early steps of infection for this important human pathogen. PMID:25902143

  9. Modulatory effects of taurine on jejunal contractility

    PubMed Central

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism. PMID:25387674

  10. Modulatory effects of taurine on jejunal contractility.

    PubMed

    Yao, Q Y; Chen, D P; Ye, D M; Diao, Y P; Lin, Y

    2014-12-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca(2+) dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  11. Prevention of epileptic seizures by taurine.

    PubMed

    El Idrissi, Abdeslem; Messing, Jeffrey; Scalia, Jason; Trenkner, Ekkhart

    2003-01-01

    Parenteral injection of kainic acid (KA), a glutamate receptor agonist, causes severe and stereotyped behavioral convulsions in mice and is used as a rodent model for human temporal lobe epilepsy. The goal of this study is to examine the potential anti-convulsive effects of the neuro-active amino acid taurine, in the mouse model of KA-induced limbic seizures. We found that taurine (43 mg/Kg, s.c.) had a significant antiepileptic effect when injected 10 min prior to KA. Acute injection of taurine increased the onset latency and reduced the occurrence of tonic seizures. Taurine also reduced the duration of tonic-clonic convulsions and mortality rate following KA-induced seizures. Furthermore, taurine significantly reduced neuronal cell death in the CA3 region of the hippocampus, the most susceptible region to KA in the limbic system. On the other hand, supplementation of taurine in drinking water (0.05%) for 4 continuous weeks failed to decrease the number or latency of partial or tonic-clonic seizures. To the contrary, we found that taurine-fed mice showed increased susceptibility to KA-induced seizures, as demonstrated by a decreased latency for clonic seizures, an increased incidence and duration of tonic-clonic seizures, increased neuronal death in the CA3 region of the hippocampus and a higher post-seizure mortality of the animals. We suggest that the reduced susceptibility to KA-induced seizures in taurine-injected mice is due to an increase in GABA receptor function in the brain which increases the inhibitory drive within the limbic system. This is supported by our in vitro data obtained in primary neuronal cultures showing that taurine acts as a low affinity agonist for GABA(A) receptors, protects neurons against kainate excitotoxic insults and modulates calcium homeostasis. Therefore, taurine is potentially capable of treating seizure-associated brain damage.

  12. Antidepressant effect of taurine in diabetic rats.

    PubMed

    Caletti, Greice; Olguins, Danielly B; Pedrollo, Elis F; Barros, Helena M T; Gomez, Rosane

    2012-10-01

    Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

  13. Perfluorocarbon facilitated O(2) transport in a hepatic hollow fiber bioreactor.

    PubMed

    Chen, Guo; Palmer, Andre F

    2009-01-01

    A mathematical model describing O(2) transport in a hepatic hollow fiber (HF) bioreactor supplemented with perfluorocarbons (PFCs) in the circulating cell culture media was developed to explore the potential of PFCs in properly oxygenating a bioartificial liver assist device (BLAD). The 2-dimensional model is based on the geometry of a commercial HF bioreactor operated under steady-state conditions. The O(2) transport model considers fluid motion of a homogeneous mixture of cell culture media and PFCs, and mass transport of dissolved O(2) in a single HF. Each HF consists of three distinct regions: (1) the lumen (conducts the homogeneous mixture of cell culture media and PFCs), (2) the membrane (physically separates the lumen from the extracapillary space (ECS), and (3) the ECS (hepatic cells reside in this compartment). In a single HF, dissolved O(2) is predominantly transported in the lumen via convection in the axial direction and via diffusion in the radial direction through the membrane and ECS. The resulting transport equations are solved using the finite element method. The calculated O(2) transfer flux showed that supplementation of the cell culture media with PFCs can significantly enhance O(2) transport to the ECS of the HF when compared with a control with no PFC supplementation. Moreover, the O(2) distribution and subsequent analysis of ECS zonation demonstrate that limited in vivo-like O(2) gradients can be recapitulated with proper selection of the operational settings of the HF bioreactor. Taken together, this model can also be used to optimize the operating conditions for future BLAD development that aim to fully recapitulate the liver's varied functions. 2009 American Institute of Chemical Engineers Biotechnol.

  14. Knockout of the murine cysteine dioxygenase gene results in severe impairment in ability to synthesize taurine and an increased catabolism of cysteine to hydrogen sulfide

    PubMed Central

    Ueki, Iori; Roman, Heather B.; Valli, Alessandro; Fieselmann, Krista; Lam, Jimmy; Peters, Rachel; Hirschberger, Lawrence L.

    2011-01-01

    Cysteine homeostasis is dependent on the regulation of cysteine dioxygenase (CDO) in response to changes in sulfur amino acid intake. CDO oxidizes cysteine to cysteinesulfinate, which is further metabolized to either taurine or to pyruvate plus sulfate. To gain insight into the physiological function of CDO and the consequence of a loss of CDO activity, mice carrying a null CDO allele (CDO+/− mice) were crossed to generate CDO−/−, CDO+/−, and CDO+/+ mice. CDO−/− mice exhibited postnatal mortality, growth deficit, and connective tissue pathology. CDO−/− mice had extremely low taurine levels and somewhat elevated cysteine levels, consistent with the lack of flux through CDO-dependent catabolic pathways. However, plasma sulfate levels were slightly higher in CDO−/− mice than in CDO+/− or CDO+/+ mice, and tissue levels of acid-labile sulfide were elevated, indicating an increase in cysteine catabolism by cysteine desulfhydration pathways. Null mice had lower hepatic cytochrome c oxidase levels, suggesting impaired electron transport capacity. Supplementation of mice with taurine improved survival of male pups but otherwise had little effect on the phenotype of the CDO−/− mice. H2S has been identified as an important gaseous signaling molecule as well as a toxicant, and pathology may be due to dysregulation of H2S production. Control of cysteine levels by regulation of CDO may be necessary to maintain low H2S/sulfane sulfur levels and facilitate the use of H2S as a signaling molecule. PMID:21693692

  15. Dietary taurine supplementation ameliorates the lethal effect of phenanthrene but not the bioaccumulation in a marine teleost, red sea bream, Pagrus major.

    PubMed

    Hano, Takeshi; Ito, Mana; Ito, Katsutoshi; Kono, Kumiko; Ohkubo, Nobuyuki

    2017-03-01

    The present study was performed to evaluate the effect of dietary taurine on the hepatic metabolic profiles of red sea bream (Pagrus major) and on phenanthrene (a polyaromatic hydrocarbon) toxicity and bioaccumulation. The fish were fed a diet supplemented with 0% (TAU0%), 0.5% (TAU0.5%), or 5% (TAU5%) taurine for 40-55d and subjected to phenanthrene acute toxicity and bioaccumulation tests. Taurine deficiency in feed severely affected the hepatic metabolic profiles of fish, which indicated a complementary physiological response to taurine deficiency. For the acute toxicity test, fish were fed the test diets for 55d and were then exposed to 0-893µg/L phenanthrene for 96h. Tolerance to phenanthrene was significantly improved by 0.5% of taurine inclusion in feed relative to TAU0%, but not by 5.0% inclusion. Reduced glutathione in the liver, which acts as an oxygen-free radical scavenger, was associated with a reduction in the toxicity of phenanthrene. For the bioaccumulation test, fish were fed the test diets for 40d and were thereafter chronically exposed to 20µg/L phenanthrene for 13d followed by depuration for 3d. The activity of hepatic biomarker, ethoxyresorufin-O-deethylase, was increased by phenanthrene exposure in the taurine inclusion groups. However, phenanthrene concentrations in the liver and muscle of fish fed TAU5.0% tended to be higher than those of fish fed TAU0% and TAU0.5% during the exposure period. These results indicate that 0.5% of taurine inclusion in feed plays an important role in the alleviation of phenanthrene toxicity but not bioaccumulation. Furthermore, larger amount of taurine inclusion (TAU5%) did not show marked beneficial effects against phenanthrene exposure. This study provides insight about a major concern of environmental contaminants into aquatic environment and can be effectively used for improvement of aquaculture. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion.

    PubMed

    Hadj-Saïd, Wahiba; Froger, Nicolas; Ivkovic, Ivana; Jiménez-López, Manuel; Dubus, Élisabeth; Dégardin-Chicaud, Julie; Simonutti, Manuel; Quénol, César; Neveux, Nathalie; Villegas-Pérez, María Paz; Agudo-Barriuso, Marta; Vidal-Sanz, Manuel; Sahel, Jose-Alain; Picaud, Serge; García-Ayuso, Diego

    2016-09-01

    Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S- and L- cones) in an animal model of induced taurine depletion. We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their retinal distribution studied using isodensity maps. The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed. This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin+cones, L-opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.

  17. Potential benefits of taurine in the prevention of skeletal muscle impairment induced by disuse in the hindlimb-unloaded rat.

    PubMed

    Pierno, Sabata; Liantonio, Antonella; Camerino, Giulia M; De Bellis, Michela; Cannone, Maria; Gramegna, Gianluca; Scaramuzzi, Antonia; Simonetti, Simonetta; Nicchia, Grazia Paola; Basco, Davide; Svelto, Maria; Desaphy, Jean-François; Camerino, Diana Conte

    2012-07-01

    Hindlimb unloading (HU) in rats induces severe atrophy and a slow-to-fast phenotype transition in postural slow-twitch muscles, as occurs in human disuse conditions, such as spaceflight or bed rest. In rats, a reduction of soleus muscle weight and a decrease of cross-sectional area (CSA) were observed as signs of atrophy. An increased expression of the fast-isoform of myosin heavy chain (MHC) showed the phenotype transition. In parallel the resting cytosolic calcium concentration (restCa) was decreased and the resting chloride conductance (gCl), which regulates muscle excitability, was increased toward the values of the fast-twitch muscles. Here, we investigated the possible role of taurine, which is known to modulate calcium homeostasis and gCl, in the restoration of muscle impairment due to 14-days-HU. We found elevated taurine content and higher expression of the taurine transporter TauT in the soleus muscle as compared to the fast-twitch extensor digitorum longus (EDL) muscle of control rats. Taurine level was reduced in the HU soleus muscle, although, TauT expression was not modified. Taurine oral supplementation (5 g/kg) fully prevented this loss, and preserved resting gCl and restCa together with the slow MHC phenotype. Taurine supplementation did not prevent the HU-induced drop of muscle weight or fiber CSA, but it restored the expression of MURF-1, an atrophy-related gene, suggesting a possible early protective effect of taurine. In conclusion, taurine prevented the HU-induced phenotypic transition of soleus muscle and might attenuate the atrophic process. These findings argue for the beneficial use of taurine in the treatment of disuse-induced muscle dysfunction.

  18. The pharmacokinetics and hepatic disposition of repaglinide in pigs: mechanistic modeling of metabolism and transport.

    PubMed

    Sjögren, Erik; Bredberg, Ulf; Lennernäs, Hans

    2012-04-02

    The predictive power of using in vitro systems in combination with physiologically based pharmacokinetic (PBPK) modeling to elucidate the relative importance of metabolism and carrier-mediated transport for the pharmacokinetics was evaluated using repaglinide as a model compound and pig as the test system. Repaglinide was chosen as model drug as previous studies in humans have shown that repaglinide is subject to both carrier-mediated influx to the liver cells and extensive hepatic metabolism. A multiple sampling site model in pig was chosen since it provides detailed in vivo information about the liver disposition. The underlying assumption was that both metabolism and carrier-mediated transport are also important for the hepatic disposition of repaglinide in pigs. Microsomes and primary hepatocytes were used for in vitro evaluation of enzyme kinetics and cellular disposition, respectively. In vitro data were generated both with and without metabolism inhibitors (ketoconazole, bezafibrate and trimethoprim) and transport inhibitors (diclofenac and quinine) providing input into a semi-PBPK model. In vivo data were also generated with and without the same enzyme and transporter inhibitors, alone and in combination. The pigs were given repaglinide as intravenous infusions with and without inhibitors in a sequential manner, i.e., a control phase and a test phase. Parameters describing the passive and carrier-mediated flux as well as metabolism were estimated in the control phase. The result from test phase was used to gain further knowledge of the findings from the control phase. The in vivo pig model enabled simultaneous sampling from plasma (pre- and postliver and peripheral) as well as from bile and urine. A semi-PBPK model consisting of 11 compartments (6 tissues + 5 sampling sites) was constructed for the mechanistic elucidation of the liver disposition, in vitro based in vivo predictions, sensitivity analyses and estimations of individual pharmacokinetic

  19. Sulfoacetate generated by Rhodopseudomonas palustris from taurine.

    PubMed

    Denger, Karin; Weinitschke, Sonja; Hollemeyer, Klaus; Cook, Alasdair M

    2004-10-01

    Genes thought to encode (a) the regulator of taurine catabolism under carbon-limiting or nitrogen-limiting conditions and (b) taurine dehydrogenase were found in the genome of Rhodopseudomonas palustris. The organism utilized taurine quantitatively as a sole source of nitrogen (but not of carbon) for aerobic and photoheterotrophic growth. No sulfate was released, and the C-sulfonate bond was recovered stoichiometrically as sulfoacetate, which was identified by mass spectrometry. An inducible sulfoacetaldehyde dehydrogenase was detected. R. palustris thus contains a pathway to generate a natural product that was previously believed to be formed solely from sulfoquinovose.

  20. Attenuation of oxidative damage to DNA by taurine and taurine analogs.

    PubMed

    Messina, S A; Dawson, R

    2000-01-01

    Taurine has been suggested to have cytoprotective actions via a number of different mechanisms. The role of taurine in protecting DNA from oxidative damage has received only limited attention. The aim of the present studies was to test the hypothesis that taurine might act to attenuate oxidative damage to DNA caused by free radicals generated by iron-stimulated catecholamine oxidation in the presence of H2O2. Calf thymus DNA (100 microg/tube) was exposed to a reaction mixture containing: ferric chloride (60 microM), H2O2 (2.8 mM) and L-dopa (100 microM). Taurine and taurine analogs were added simultaneously to determine their effects to prevent oxidative damage to DNA. The reaction was carried out for 1 hour at 37 degrees C and terminated by rapid freezing in an ethanol/dry ice bath. The DNA was precipitated with ethanol and subsequently hydrolyzed with formic acid under vacuum. The hydroxylated bases were separated by HPLC and detected electrochemically. All experiments were replicated a minimum of 5 times. Taurine (20 mM) was found to reduce (p<0.05) damage to DNA as indexed by reductions in the formation of 5-OH-uracil (49% decrease), 8-OH adenine (37% decrease), and 8-OH guanine (21% decrease). Taurine had minimal effects to reduce the formation of 5-OH cytosine (<7% decrease). Taurine (20 mM) also increased total DNA recovery after damage 36-40% and increased total undamaged guanine approximately 32%. 5-OH Uracil formation could be reduced (p<0.05) by 1 mM taurine and 8-OH-adenine formation was reduced (p<0.05) by 5 mM taurine. Studies were conducted with various amino acid analogs and total base adduct formation was reduced by 20 mM beta-alanine (30% decrease), lysine (58% decrease) and glutathione (88% decrease). When tested at 20 mM, both hypotaurine and homotaurine provided greater protection against DNA damage than taurine, whereas isethionic acid provided a similar level of protection as taurine. Using identical conditions as the assays for base

  1. Taurine Boosts Cellular Uptake of Small D-Peptides for Enzyme-Instructed Intracellular Molecular Self-Assembly.

    PubMed

    Zhou, Jie; Du, Xuewen; Li, Jie; Yamagata, Natsuko; Xu, Bing

    2015-08-19

    Due to their biostability, D-peptides are emerging as an important molecular platform for biomedical applications. Being proteolytically resistant, D-peptides lack interactions with endogenous transporters and hardly enter cells. Here we show that taurine, a natural amino acid, drastically boosts the cellular uptake of small D-peptides in mammalian cells by >10-fold, from 118 μM (without conjugating taurine) to >1.6 mM (after conjugating taurine). The uptake of a large amount of the ester conjugate of taurine and D-peptide allows intracellular esterase to trigger intracellular self-assembly of the D-peptide derivative, further enhancing their cellular accumulation. The study on the mechanism of the uptake reveals that the conjugates enter cells via both dynamin-dependent endocytosis and macropinocytosis, but likely not relying on taurine transporters. Differing fundamentally from the positively charged cell-penetrating peptides, the biocompatibility, stability, and simplicity of the enzyme-cleavable taurine motif promise new ways to promote the uptake of bioactive molecules for countering the action of efflux pump and contributing to intracellular molecular self-assembly.

  2. A case of taurine-containing drink induced anaphylaxis.

    PubMed

    Lee, Seung-Eun; Lee, Suh-Young; Jo, Eun-Jung; Kim, Mi-Young; Yang, Min-Suk; Chang, Yoon-Seok; Kim, Sae-Hoon

    2013-01-01

    Taurine is one of most abundant free amino acids in mammalian tissue. It has been used for various health functional foods as a main ingredient in food industry. A 33-year-old female patient repeatedly experienced generalized itching, urticaria, dyspnea and dizziness after drinking taurine-containing drinks. The patient showed positive response to oral challenge tests with taurine-containing drinks. The patient also showed positive response with synthetic taurine but not with natural taurine. Skin prick test and basophil activation test with the synthetic taurine were negative. To our knowledge, there has been no report of taurine-induced hypersensitivity reactions. We herein report the first case of taurine-containing drink induced anaphylaxis, especially by synthetic taurine.

  3. Long-lasting enhancement of corticostriatal transmission by taurine: role of dopamine and acetylcholine.

    PubMed

    Chepkova, A N; Sergeeva, O A; Haas, H L

    2005-06-01

    1. Taurine applied to mouse brain slices evokes a long-lasting enhancement (LLE) of corticostriatal synaptic transmission, LLE(TAU). 2. The occurrence of LLE(TAU) was significantly decreased in the presence of the specific antagonists at either D1 (SCH23390) or D2 (raclopride) dopamine (DA) receptors. 3. LLE(TAU) was prevented by scopolamine, a muscarinic antagonist, and significantly suppressed by the nicotinic antagonist mecamylamine. 4. Thus, dopaminergic and cholinergic mechanisms, in concert with the taurine transporter and glycine receptors, contribute critically to the induction of corticostriatal LLE(TAU).

  4. The ubiquitin-proteasome system and autophagy are defective in the taurine-deficient heart.

    PubMed

    Jong, Chian Ju; Ito, Takashi; Schaffer, Stephen W

    2015-12-01

    Taurine depletion leads to impaired mitochondrial function, as characterized by reduced ATP production and elevated superoxide generation. These defects can fundamentally alter cardiomyocyte function and if left unchanged can result in cell death. To protect against these stresses, cardiomyocytes possess quality control processes, such as the ubiquitin-proteasome system (UPS) and autophagy, which can rejuvenate cells through the degradation of damaged proteins and organelles. Hence, the present study tested the hypothesis that reactive oxygen species generated by damaged mitochondria initiates UPS and autophagy in the taurine-deficient heart. Using transgenic mice lacking the taurine transporter (TauTKO) as a model of taurine deficiency, it was shown that the levels of ubiquitinated protein were elevated, an effect associated with a decrease in ATP-dependent 26S β5 proteasome activity. Treating the TauTKO mouse with the mitochondria-specific antioxidant, mitoTEMPO, largely abolished the increase in ubiquitinated protein content. The TauTKO heart was also associated with impaired autophagy, characterized by an increase in the initiator, Beclin-1, and autophagosome content, but a defect in the generation of active autophagolysosomes. Although mitoTEMPO treatment only restores the oxidative balance within the mitochondria, it appeared to completely disrupt the crosstalk between the damaged mitochondria and the quality control processes. Thus, mitochondrial oxidative stress is the main trigger initiating the quality control systems in the taurine-deficient heart. We conclude that the activation of the UPS and autophagy is another fundamental function of mitochondria.

  5. Reaction of (/sup 3/H)-taurine maleimide with platelet surface thiols

    SciTech Connect

    Karl, D.W.; Mills, D.C.B.

    1986-05-01

    Taurine Maleimide (2-maleimidoethanesulfonate, TM) was synthesized from (2-/sup 3/H)-taurine and methoxycarbonylmaleimide (MCM). The yield of a 1 ..mu..mol synthesis approached 100% (based on taurine) when MCM was used in 4-fold excess. The product (TM*) was purified by ion exchange chromatography. TM* reacted irreversibly with thiol groups on the surface of washed human platelets, leading to incorporation of radioactivity into platelet pellets. Incorporation was blocked by cysteine, mercuribenzenesulfonate (MBS), dithiobisnitrobenzoate, and N-ethylmaleimide, but not by taurine or by inhibitors of anion transport. Reaction of TM* with platelets showed the dependence on time and concentration characteristics of a bimolecular reaction. The number of reactive sites ranged from 1 to 5 x 10/sup 5//platelet, and the apparent rate constant from 1 to 3 x 10/sup 3//(M x min). TM was less effective than MBS as an inhibitor of platelet aggregation induced by several agents. TM had no effect on the uptake of serotonin, taurine, or phosphate by the platelets, processes which are sensitive to MBS. These differences, considered with the similarity in size and charge of TM and MBS, suggest that classes of thiols defined as exofacial by their accessibility to MBS can differ substantially in their reactivity with other impermeant reagents.

  6. Tissue Taurine Depletion Alters Metabolic Response to Exercise and Reduces Running Capacity in Mice

    PubMed Central

    Yoshikawa, Natsumi; Schaffer, Stephen W.

    2014-01-01

    Taurine is a sulfur-containing amino acid found in very high concentration in skeletal muscle. Taurine deficient mice engineered by knocking out the taurine transporter gene exhibit skeletal muscle wasting, structural defects, and exercise intolerance. In the present study, we investigated the mechanism underlying the development of metabolic abnormalities and exercise intolerance in muscle of the TauTKO phenotype. Running speed and endurance time of TauTKO mice were lower than those of control mice. Blood lactate level was elevated by >3-fold during treadmill running in TauTKO mice but remained largely unaltered by exercise in WT mice. Blood glucose was cleared faster during treadmill running in TauTKO mice than WT mice. AMP-activated kinase (AMPK) β-2 subunit was reduced in TauTKO muscle concomitant with a reduction in α1 and α2 subunits of AMPK. The level of PPARα and its targets, Gpx3, Cpt2, and Echs1, were also decreased in TauTKO muscle. Collectively, taurine depletion impairs metabolic adaptation to exercise in skeletal muscle, a phenomenon associated with a downregulation of AMPK and diminished NADH utilization by the mitochondrial respiratory chain. These findings suggest a crucial role of taurine in regulating energy metabolism in skeletal muscle of exercising TauTKO mice, changes that contribute to impaired exercise endurance. PMID:25478210

  7. Tissue taurine depletion alters metabolic response to exercise and reduces running capacity in mice.

    PubMed

    Ito, Takashi; Yoshikawa, Natsumi; Schaffer, Stephen W; Azuma, Junichi

    2014-01-01

    Taurine is a sulfur-containing amino acid found in very high concentration in skeletal muscle. Taurine deficient mice engineered by knocking out the taurine transporter gene exhibit skeletal muscle wasting, structural defects, and exercise intolerance. In the present study, we investigated the mechanism underlying the development of metabolic abnormalities and exercise intolerance in muscle of the TauTKO phenotype. Running speed and endurance time of TauTKO mice were lower than those of control mice. Blood lactate level was elevated by >3-fold during treadmill running in TauTKO mice but remained largely unaltered by exercise in WT mice. Blood glucose was cleared faster during treadmill running in TauTKO mice than WT mice. AMP-activated kinase (AMPK) β-2 subunit was reduced in TauTKO muscle concomitant with a reduction in α1 and α2 subunits of AMPK. The level of PPARα and its targets, Gpx3, Cpt2, and Echs1, were also decreased in TauTKO muscle. Collectively, taurine depletion impairs metabolic adaptation to exercise in skeletal muscle, a phenomenon associated with a downregulation of AMPK and diminished NADH utilization by the mitochondrial respiratory chain. These findings suggest a crucial role of taurine in regulating energy metabolism in skeletal muscle of exercising TauTKO mice, changes that contribute to impaired exercise endurance.

  8. Taurine suppresses osteoblastic differentiation of aortic valve interstitial cells induced by beta-glycerophosphate disodium, dexamethasone and ascorbic acid via the ERK pathway.

    PubMed

    Feng, Xiang; Li, Jian-ming; Liao, Xiao-bo; Hu, Ye-rong; Shang, Bao-peng; Zhang, Zhi-yuan; Yuan, Ling-qing; Xie, Hui; Sheng, Zhi-feng; Tang, Hao; Zhang, Wei; Gu, Lu; Zhou, Xin-min

    2012-10-01

    Aortic valve calcification (AVC) is an active process characterized by osteoblastic differentiation of the aortic valve interstitial cells (AVICs). Taurine is a free β-amino acid and plays important physiological roles including protective effect of cardiovascular events. To evaluate the possible role of taurine in AVC, we isolated human AVICs from patients with type A dissection without leaflet disease. We demonstrated that the cultured AVICs express SM α-actin, vimentin and taurine transporter (TAUT), but not CD31, SM-myosin or desmin. We also established the osteoblastic differentiation model of the AVICs induced by pro-calcific medium (PCM) containing β-glycerophosphate disodium, dexamethasone and ascorbic acid in vitro. The results showed that taurine attenuated the PCM-induced osteoblastic differentiation of AVICs by decreasing the alkaline phosphate (ALP) activity/expression and the expression of the core binding factor α1 (Cbfα1) in a dose-dependent manner (reaching the maximum protective effect at 10 mM), and taurine (10 mM) inhibited the mineralization level of AVICs in the form of calcium content significantly. Furthermore, taurine activated the extracellular signal-regulated protein kinase (ERK) pathway via TAUT, and the inhibitor of ERK (PD98059) abolished the effect of taurine on both ALP activity/expression and Cbfα1 expression. These results suggested that taurine could inhibit osteoblastic differentiation of AVIC via the ERK pathway.

  9. Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression.

    PubMed

    Donepudi, Ajay C; Cheng, Qiuqiong; Lu, Zhenqiang James; Cherrington, Nathan J; Slitt, Angela L

    2016-04-01

    Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor- and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression

    PubMed Central

    Donepudi, Ajay C.; Cheng, Qiuqiong; Lu, Zhenqiang James; Cherrington, Nathan J.

    2016-01-01

    Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor– and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport. PMID:26847773

  11. Effects of taurine administration in rat skeletal muscles on exercise.

    PubMed

    Yatabe, Yoshihisa; Miyakawa, Shumpei; Miyazaki, Teruo; Matsuzaki, Yasushi; Ochiai, Naoyuki

    2003-01-01

    To investigate the effects of taurine administration on exercise, we studied taurine concentrations in rat skeletal muscles after endurance running and the duration of running time to exhaustion, with and without taurine administration. For study 1 we divided 40 male SD rats into two groups: endurance exercise group ( n = 20) and sedentary control group ( n = 20). Each was further divided into two groups; one received distilled water ( n = 10) and the other taurine solution in water 0.5 g/kg/day orally ( n = 10) for 2 weeks. The exercise group performed treadmill running (60 min) once only after their nursing period. For study 2, we divided 10 male SD rats into two groups; one ( n = 5) received taurine 0.5 g/kg/day, and the other ( n = 5) received no taurine for 2 weeks; the two groups then performed treadmill running to exhaustion. In study 1, taurine administration increased taurine concentrations in leg skeletal muscles, whereas the concentrations were significantly lower in the exercised groups without taurine administration. Taurine administration reduced the decrease in taurine concentration in skeletal muscles on exercise. In study 2, the duration of running time to exhaustion was significantly increased by taurine administration. We concluded that peroral administration of taurine maintains the taurine concentration in skeletal muscle on exercise and up-regulates physical endurance.

  12. Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells.

    PubMed

    Villumsen, Kasper Rømer; Duelund, Lars; Lambert, Ian Henry

    2010-11-01

    In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-β-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to 60±5% of the control value. Electron spin resonance data indicate a concomitant disruption of cholesterol-rich micro-domains. Active taurine uptake, cellular taurine content, and cell volume are reduced by 50, 20 and 20% compared to control values, respectively, whereas the passive taurine release is increased 4.5-fold under isotonic conditions following cholesterol depletion. However, taurine release under isotonic conditions is insensitive to DIDS and inhibitors of the volume-regulated anion channel. Uptake and release of meAIB are similarly affected following cholesterol depletion. Kinetic analysis reveals that cholesterol depletion increases TauT's affinity toward taurine but reduces its maximal transport capacity. Cholesterol depletion has no impact on TauT regulation by protein kinases A and C. Phospholipase A2 activity, which is required for the activation of volume-sensitive organic anion channel (VSOAC), is increased under isotonic and hypotonic conditions following cholesterol depletion, whereas taurine release under hypotonic conditions is reduced following cholesterol depletion. Hence, acute cholesterol depletion of Ehrlich Lettré cells leads to reduced TauT and VSOAC activities and at the same time increases the release of organic osmolytes via a leak pathway different from the volume-sensitive pathways for amino acids and anions.

  13. Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance

    PubMed Central

    Dietrich, Christoph G; Götze, Oliver; Geier, Andreas

    2016-01-01

    Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests. PMID:26755861

  14. Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors.

    PubMed

    Emami Riedmaier, A; Burk, O; van Eijck, B A C; Schaeffeler, E; Klein, K; Fehr, S; Biskup, S; Müller, S; Winter, S; Zanger, U M; Schwab, M; Nies, A T

    2016-08-01

    Human organic anion transporter 7 (OAT7, SLC22A9) is a hepatic transport protein poorly characterized so far. We therefore sought to identify novel OAT7 substrates and factors contributing to variable hepatic OAT7 expression. Using OAT7-expressing cells, pravastatin was identified as a substrate. Hepatic SLC22A9/OAT7 mRNA and protein expression varied 28-fold and 15-fold, respectively, in 126 Caucasian liver samples. Twenty-four variants in SLC22A9 were genotyped, including three rare missense variants (rs377211288, rs61742518, rs146027075), which occurred only heterozygously. No variant significantly affected hepatic SLC22A9/OAT7 expression. The three missense variants, however, showed functional consequences when expressed in vitro. Hepatic nuclear factor 4-alpha (HNF4α) emerged as a major transcriptional regulator of SLC22A9 by a series of in silico and in vitro analyses. In conclusion, pravastatin is the first identified OAT7 drug substrate. Substantial inter-individual variability in hepatic OAT7 expression, majorly driven by HNF4α, may contribute to pravastatin drug disposition and might affect response.The Pharmacogenomics Journal advance online publication, 4 August 2015; doi:10.1038/tpj.2015.55.

  15. Caffeine and taurine enhance endurance performance.

    PubMed

    Imagawa, T F; Hirano, I; Utsuki, K; Horie, M; Naka, A; Matsumoto, K; Imagawa, S

    2009-07-01

    Caffeine enhances endurance performance; however, its effect on accumulated lactate remains unclear. Conversely, taurine, which also enhances endurance performance, decreases accumulated lactate. In this study, the effect of combination of caffeine and taurine on endurance performance was assessed. Mice ran on a treadmill, and the accumulated lactate was measured. In addition, muscle fibers from the gastrocnemius muscle of the mice were stained with ATPase and analyzed. The use of caffeine and taurine over a 2 week period enhanced endurance performance. Moreover, taurine significantly decreased the accumulated concentration of lactate over long running distances. However, the diameter of the cross-sections and ratios of Types I, IIA, and IIB muscle fibers were not affected.

  16. Dietary inclusion level and time effects of taurine on broiler performance, meat quality, oxidative status and muscle taurine content.

    PubMed

    Huang, C X; Wang, B; Min, Z; Yuan, J

    2014-01-01

    Two experiments were conducted to investigate the effect of taurine on growth performance, meat quality, oxidative status and muscle taurine content in broilers. In Experiment 1, 50 one-day-old male Cobb chicks were given a diet supplemented with 0, 0.125, 0.50, 2.00 or 8.00 g/kg taurine from 1 to 42 d of age. In Experiment 2, 80 22-d-old male Cobb chicks were given a diet supplemented with 4.00 g/kg taurine for 0, 1, 2 or 3 weeks. Taurine contents of thigh and breast muscle increased linearly with increasing dietary taurine. Taurine supplementation for 1, 2 and 3 weeks significantly increased the taurine content of breast muscle. The taurine contents of liver and thigh meat were significantly increased by taurine supplementation for 3 weeks. The taurine contents of thigh and breast meat from broilers given a diet supplemented with 4 g/kg taurine for 3 weeks increased to 1.89 times the concentrations of the control group. There were no detrimental effects on growth performance, breast or thigh muscle yield, pH value or drip-water loss, and taurine supplementation did not affect the serum carbonyl content. Serum malondialdehyde concentration was significantly decreased by taurine supplementation for 1, 2 or 3 weeks.

  17. Effect of taurine supplementation on growth and development in preterm or low birth weight infants.

    PubMed

    Verner, A; Craig, S; McGuire, W

    2007-10-17

    Taurine is the most abundant free amino acid in breast milk. Evidence exists that taurine has important roles in intestinal fat absorption, hepatic function, and auditory and visual development in preterm or low birth weight infants. Observational data suggest that relative taurine deficiency during the neonatal period is associated with adverse long-term neurodevelopmental outcomes in preterm infants. Current standard practice is to supplement formula milk and parenteral nutrition solutions with taurine. To assess the effect of providing supplemental taurine for enterally or parenterally fed preterm or low birth weight infants on growth and development. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - June 2007), EMBASE (1980 - June 2007), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared taurine supplementation versus no supplementation in preterm or low birth weight newborn infants. Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors, and synthesis of data using relative risk, risk difference and weighted mean difference. Nine small trials were identified. In total, 189 infants participated. Most participants were greater than 30 weeks gestational age at birth and were clinically stable. In eight of the studies, taurine was given enterally with formula milk. Only one small trial assessed parenteral taurine supplementation. Taurine supplementation increased intestinal fat absorption [weighted mean difference 4.0 (95% confidence interval 1.4, 6.6) percent of intake]. However, meta-analyses did not reveal any statistically significant effects on growth parameters assessed during the neonatal period or until three to four

  18. HPLC Determination of Taurine in Sports Drinks

    NASA Astrophysics Data System (ADS)

    Orth, Dale L.

    2001-06-01

    The amino acid taurine (2-aminoethanesulfonic acid) is present as a nutritional supplement in many sports drinks. An experiment, suitable for a junior-senior level instrumental analysis course, is described to measure the amount of taurine in these sports drinks. A pre-column derivatization with Sanger's reagent, 2,4-dinitrofluorobenzene, is followed by an HPLC separation utilizing a gradient elution, and detection at 360 nm.

  19. Taurine zinc solid dispersions enhance bile-incubated L02 cell viability and improve liver function by inhibiting ERK2 and JNK phosphorylation during cholestasis.

    PubMed

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lai, Xiaofang; Xu, Donghui

    2016-07-29

    Dietary intakes of taurine and zinc are associated with decreased risk of liver disease. In this study, solid dispersions (SDs) of a taurine zinc complex on hepatic injury were examined in vitro using the immortalized human hepatocyte cell line L02 and in a rat model of bile duct ligation. Sham-operated and bile duct ligated Sprague-Dawley rats were treated with the vehicle alone or taurine zinc (40, 80, 160mg/kg) for 17days. Bile duct ligation significantly increased blood lipid levels, and promoted hepatocyte apoptosis, inflammation and compensatory biliary proliferation. In vitro, incubation with bile significantly reduced L02 cell viability; this effect was significantly attenuated by pretreatment with SP600125 (a JNK inhibitor) and enhanced when co-incubated with taurine zinc SDs. In vivo, administration of taurine zinc SDs decreased serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner and attenuated the increases in serum total bilirubin, total cholesterol and low density lipoprotein cholesterol levels after bile duct ligation. Additionally, taurine zinc SDs downregulated the expression of interleukin-1β and inhibited the phosphorylation of Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase2 (ERK2) in the liver after bile duct ligation. Moreover, taurine zinc SDs had more potent blood lipid regulatory and anti-apoptotic effects than the physical mixture of taurine and zinc acetate. Therefore, we speculate that taurine zinc SDs protect liver function at least in part via a mechanism linked to reduce phosphorylation of JNK and ERK2, which suppresses inflammation, apoptosis and cholangiocyte proliferation during cholestasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Effect of chlorpromazine on hepatic transport of indocyanine green in rats.

    PubMed

    Tsao, S C; Sawada, Y; Iga, T; Hanano, M

    1983-03-15

    The effect of chlorpromazine hydrochloride (CPZ) on the hepatic transport of indocyanine green (ICG) was studied in the rat, in an attempt to elucidate the mechanisms of hepatotoxicity of CPZ in vivo, by comparing the pharmacokinetic parameters of ICG after bolus and chronic administration of CPZ. Delays were shown in both plasma disappearance and biliary excretion of ICG in the CPZ-treated rats (10 and 15 mg/kg intraportal bolus administration). Significant decreases were observed in the pharmacokinetic parameters, V2 and total body clearance (CLtot) in CPZ 10 mg/kg treated rats and k34, V2 and CLtot in CPZ 15 mg/kg treated rats, while a significant increase was observed in k21 in both CPZ-treated groups; V1 was not altered. The apparent liver-to-plasma concentration ratio (Kp,app) of ICG at 50 min after i.v. administration was decreased significantly in CPZ 15 mg/kg treated rats when compared to control rats, suggesting an alteration in the distribution of ICG to the liver by CPZ. Bile flow rates decreased immediately after bolus intraportal administration of CPZ in both CPZ-treated groups, and they then returned progressively to the basal levels. The output of bile acids was also inhibited by CPZ in a time-dependent and reversible manner and the bile acid independent fraction of bile flow was decreased significantly in both CPZ-treated groups. Chronic treatment with CPZ (10 or 20 mg/kg, i.p., per day for 3 weeks) did not alter either the pharmacokinetic parameters or the bile secretion profile of ICG, although there were significant decreases in body and liver weights in CPZ-treated groups. This may have been due to the rapid metabolism and excretion of CPZ in the rat when compared to humans. It is proposed that the acute toxic effect of CPZ on hepatic transport of ICG in the rat may be due mainly to the time-dependent and reversible cholestasis induced by CPZ, and that chronic treatment with CPZ may not alter the hepatic transport of ICG in the rat.

  1. Interaction of dietary cholesterol and triglycerides in the regulation of hepatic low density lipoprotein transport in the hamster.

    PubMed Central

    Spady, D K; Dietschy, J M

    1988-01-01

    These studies report the effects of dietary cholesterol and triglyceride on rates of receptor-dependent and receptor-independent LDL transport in the liver of the hamster. In animals fed diets enriched with 0.1, 0.25, or 1% cholesterol for 1 mo, receptor-dependent LDL transport in the liver was suppressed by 43, 63, and 77%, respectively, and there were reciprocal changes in plasma LDL-cholesterol concentrations. In addition, dietary triglycerides modified the effect of dietary cholesterol on hepatic LDL transport and plasma LDL concentrations so that at each level of cholesterol intake, polyunsaturated triglycerides diminished and saturated triglycerides accentuated the effect of dietary cholesterol. When animals were raised from weaning on diets containing small amounts of cholesterol, the decline in receptor-dependent LDL transport was nearly abolished by the addition of polyunsaturated or monounsaturated triglycerides, but was markedly augmented by the addition of saturated lipids. When animals raised on diets containing cholesterol and saturated triglycerides were returned to the low cholesterol, low triglyceride control diet, hepatic receptor-dependent LDL transport and plasma LDL-cholesterol concentrations returned essentially to normal within 2 wk. Neither receptor-independent LDL transport nor the receptor-dependent uptake of asialofetuin was significantly altered by dietary cholesterol or triglyceride suggesting that the effect of these lipids on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physiochemical properties of hepatic membranes. These studies demonstrate the important role of saturated triglycerides in augmenting the effect of cholesterol in suppressing hepatic LDL receptor activity and elevating LDL-cholesterol levels. PMID:2448340

  2. Gene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters

    PubMed Central

    Yang, Lun; Price, Elvin T.; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

    2013-01-01

    Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications. PMID:23637747

  3. [Taurine. Effect on exotrophia and metabolism in mammals and fish].

    PubMed

    Kuz'mina, V V; Gavrovskaia, L K; Ryzhova, O V

    2010-01-01

    Data have been presented on the taurine content in various mammalian and fish tissues as well as on pathways of its formation, turnover, and numerous functions. Based on comparison of the character of the taurine effects on various animal functions as well as of the fact of the presence of taurine in the more ancient by origin potential objects of the mammalian and fish nutrition, it is suggested that the taurine polyfunctionality has appeared at different stages of the biota.

  4. Interactions of taurine and dopamine in the striatum.

    PubMed

    Kontro, P

    1987-01-01

    Both spontaneous and K+-stimulated taurine release from rat striatal slices were affected by dopamine and apomorphine, suggesting that dopaminergic systems are able to modulate taurine release. K+-stimulated dopamine release was potentiated by taurine, which effect may not involve dopamine autoreceptors. Taurine was able to inhibit spiperone binding to striatal membranes in a uncompetitive manner and thus interfere with the function of dopaminergic receptors.

  5. Taurine reduction in anaerobic respiration of Bilophila wadsworthia RZATAU.

    PubMed

    Laue, H; Denger, K; Cook, A M

    1997-05-01

    Organosulfonates are important natural and man-made compounds, but until recently (T. J. Lie, T. Pitta, E. R. Leadbetter, W. Godchaux III, and J. R. Leadbetter. Arch. Microbiol. 166:204-210, 1996), they were not believed to be dissimilated under anoxic conditions. We also chose to test whether alkane- and arenesulfonates could serve as electron sinks in respiratory metabolism. We generated 60 anoxic enrichment cultures in mineral salts medium which included several potential electron donors and a single organic sulfonate as an electron sink, and we used material from anaerobic digestors in communal sewage works as inocula. None of the four aromatic sulfonates, the three unsubstituted alkanesulfonates, or the N-sulfonate tested gave positive enrichment cultures requiring both the electron donor and electron sink for growth. Nine cultures utilizing the natural products taurine, cysteate, or isethionate were considered positive for growth, and all formed sulfide. Two clearly different pure cultures were examined. Putative Desulfovibrio sp. strain RZACYSA, with lactate as the electron donor, utilized sulfate, aminomethanesulfonate, taurine, isethionate, and cysteate, converting the latter to ammonia, acetate, and sulfide. Strain RZATAU was identified by 16S rDNA analysis as Bilophila wadsworthia. In the presence of, e.g., formate as the electron donor, it utilized, e.g., cysteate and isethionate and converted taurine quantitatively to cell material and products identified as ammonia, acetate, and sulfide. Sulfite and thiosulfate, but not sulfate, were utilized as electron sinks, as was nitrate, when lactate was provided as the electron donor and carbon source. A growth requirement for 1,4-naphthoquinone indicates a menaquinone electron carrier, and the presence of cytochrome c supports the presence of an electron transport chain. Pyruvate-dependent disappearance of taurine from cell extracts, as well as formation of alanine and release of ammonia and acetate, was

  6. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  7. Effects of graded taurine levels on juvenile cobia

    USDA-ARS?s Scientific Manuscript database

    Taurine, which has multiple important physiological roles in teleost fish and mammals, is an amino acid not found in alternative protein sources not derived from animals. Although taurine is found in fish-meal-based feeds, its high water solubility leads to lower taurine levels in reduction-process-...

  8. Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation.

    PubMed

    Kessler, E C; Gross, J J; Bruckmaier, R M; Albrecht, C

    2014-09-01

    The transition from the nonlactating to the lactating state represents a critical period for dairy cow lipid metabolism because body reserves have to be mobilized to meet the increasing energy requirements for the initiation of milk production. The purpose of this study was to provide a comprehensive overview on cholesterol homeostasis in transition dairy cows by assessing in parallel plasma, milk, and hepatic tissue for key factors of cholesterol metabolism, transport, and regulation. Blood samples and liver biopsies were taken from 50 multiparous Holstein dairy cows in wk 3 antepartum (a.p.), wk 1 postpartum (p.p.), wk 4 p.p., and wk 14 p.p. Milk sampling was performed in wk 1, 4, and 14 p.p. Blood and milk lipid concentrations [triglycerides (TG), cholesterol, and lipoproteins], enzyme activities (phospholipid transfer protein and lecithin:cholesterol acyltransferase) were analyzed using enzymatic assays. Hepatic gene expression patterns of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGC) synthase 1 (HMGCS1) and HMGC reductase (HMGCR), sterol regulatory element-binding factor (SREBF)-1 and -2, microsomal triglyceride transfer protein (MTTP), ATP-binding cassette transporter (ABC) A1 and ABCG1, liver X receptor (LXR) α and peroxisome proliferator activated receptor (PPAR) α and γ were measured using quantitative RT-PCR. Plasma TG, cholesterol, and lipoprotein concentrations decreased from wk 3 a.p. to a minimum in wk 1 p.p., and then gradually increased until wk 14 p.p. Compared with wk 4 p.p., phospholipid transfer protein activity was increased in wk 1 p.p., whereas lecithin:cholesterol acyltransferase activity was lowest at this period. Total cholesterol concentration and mass, and cholesterol concentration in the milk fat fraction decreased from wk 1 p.p. to wk 4 p.p. Both total and milk fat cholesterol concentration were decreased in wk 4 p.p. compared with wk 1 and 14 p.p. The mRNA abundance of genes involved in cholesterol synthesis (SREBF-2, HMGCS1, and

  9. Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis.

    PubMed

    Zhang, Ying; Zhao, Xin; Chang, Yanzhong; Zhang, Yuanyuan; Chu, Xi; Zhang, Xuan; Liu, Zhenyi; Guo, Hui; Wang, Na; Gao, Yonggang; Zhang, Jianping; Chu, Li

    2016-06-15

    Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n=8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined by molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The mitochondrial permeability transition and taurine.

    PubMed

    Palmi, M; Youmbi, G T; Sgaragli, G; Meini, A; Benocci, A; Fusi, F; Frosini, M; Della Corte, L; Davey, G; Tipton, K F

    2000-01-01

    Perturbed cellular calcium homeostasis has been implicated in both apoptosis and necrosis, but the role of altered mitochondrial calcium handling in the cell death process is unclear. Recently we found that taurine, a naturally occurring amino acid potentiates Ca2+ sequestration by rat liver mitochondria. These data, which accounted for the taurine antagonism on Ca2+ release induced by the neurotoxins 1-methyl-4-phenylpyridinium plus 6-hydroxy dopamine previously reported, prompted us to investigate the effects of taurine on the permeability transition (PT) induced experimentally by high Ca2+ plus phosphate concentrations. The parameters used to measure the PT were, mitochondrial swelling, cytochrome c release and membrane potential changes. The results showed that, whereas taurine failed to reverse changes of these parameters, cyclosporin A completely reversed them. Even though these results exclude a role in PT regulation under such gross insult conditions, they cannot exclude an important role for taurine in controlling pore-opening under milder more physiological PT-inducing conditions.

  11. Niemann-Pick C1-Like 1 (NPC1L1) Protein in Intestinal and Hepatic Cholesterol Transport

    PubMed Central

    Jia, Lin; Betters, Jenna L.; Yu, Liqing

    2014-01-01

    Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases. PMID:20809793

  12. Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats.

    PubMed

    Flora, Swaran J S; Chouhan, Swapnila; Kannan, Gurusamy M; Mittal, Megha; Swarnkar, Harimohan

    2008-01-01

    Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood delta-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co

  13. Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats

    PubMed Central

    Chouhan, Swapnila; Kannan, Gurusamy M; Mittal, Megha; Swarnkar, Harimohan

    2008-01-01

    Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co-administration of

  14. Taurine allosterically modulates flunitrazepam binding to synaptic membranes.

    PubMed

    Quinn, M R; Miller, C L

    1992-09-01

    Taurine is hypothesized to exert its inhibitory neuromodulatory effects, in part, by interaction with the GABAA receptor. Although taurine displaces GABA agonist binding to synaptic membranes, its allosteric effects on the benzodiazepine recognition site of the GABAA receptor complex is unsettled. We determined the effects of taurine on [3H]flunitrazepam (Flu) binding to well-washed, frozen-thawed synaptic membranes prepared from rat cortex. Comparative binding studies were conducted at 37 degrees C and on ice (0-4 degrees C). At 37 degrees C taurine increased Flu binding in a concentration dependent way by interaction with a bicuculline sensitive site, similar to GABA. Taurine increased Flu binding by causing a decrease in KD. The maximal effectiveness of taurine on Flu binding could not be increased further by addition of GABA. In contrast, the maximal stimulation of Flu binding by GABA was decreased by addition of taurine to the level attained by taurine alone. These mixed agonist/antagonist effects of taurine are pharmacologically specific and qualify taurine as a partial GABA agonist in this type of allosteric interaction. However, taurine causes opposite effects on Flu binding when measured at 0-4 degrees C: taurine interacts with a bicuculline insensitive site to inhibit Flu binding by increasing the KD. Taurine inhibition of Flu binding is not overcome by increasing concentrations of GABA. Although the mechanism of taurine inhibition of Flu binding at 0-4 degrees C is unclear, it may be an indirect effect of taurine interaction with membrane phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Mechanisms of hepatic transport of cyclosporin A: an explanation for its cholestatic action?

    PubMed Central

    Fricker, G.; Fahr, A.

    1997-01-01

    The hepatic transport of the immunosuppressive Cyclosporin A (CyA) was studied using liposomal phospholipid membranes, freshly isolated rat hepatocytes and bile canalicular plasma membrane vesicles from rat liver. The Na(+)-dependent, saturable uptake of the bile acid 3H-taurocholate into isolated rat liver cells was apparently competitively inhibited by CyA. However, the uptake of CyA into the cells was neither saturable, nor temperature-dependent nor Na(+)-dependent, nor could it be inhibited by bile salts or CyA-derivatives, indicating passive diffusion. In steady state depolarization fluorescence studies, CyA caused a concentration-dependent decrease of anisotropy, indicating a membrane fluidizing effect. Ion flux experiments demonstrated that CyA dramatically increases the permeability of Na+ and Ca2+ across phospholipid membranes in a dose- and time-dependent manner, suggesting a iontophoretic activity that might have a direct impact on cellular ion homeostasis and regulation of bile acid uptake. Photoaffinity labeling with a [3H]-labeled photolabile CyA-derivative resulted in the predominant incorporation of radioactivity into a membrane polypeptide with an apparent molecular weight of 160,000 and a minor labeling of polypeptides with molecular weights of 85,000-90,000. In contrast, use of a photolabile bile acid resulted in the labeling of a membrane polypeptide with an apparent molecular weight of 110,000, representing the bile canalicular bile acid carrier. The photoaffinity labeling as well as CyA transport by canalicular membrane vesicles were inhibited by CyA and the p-glycoprotein substrates daunomycin and PSC-833, but not by taurocholate, indicating that CyA is excreted by p-glycoprotein. CyA uptake by bile canalicular membrane vesicles was ATP-dependent and could not be inhibited by taurocholate. CyA caused a decrease in the maximum amount of bile salt accumulated by the vesicles with time. However, initial rates of [3H]-taurocholate uptake within

  16. Taurine Inhibits K+-Cl− Cotransporter KCC2 to Regulate Embryonic Cl− Homeostasis via With-no-lysine (WNK) Protein Kinase Signaling Pathway*

    PubMed Central

    Inoue, Koichi; Furukawa, Tomonori; Kumada, Tatsuro; Yamada, Junko; Wang, Tianying; Inoue, Rieko; Fukuda, Atsuo

    2012-01-01

    GABA inhibits mature neurons and conversely excites immature neurons due to lower K+-Cl− cotransporter 2 (KCC2) expression. We observed that ectopically expressed KCC2 in embryonic cerebral cortices was not active; however, KCC2 functioned in newborns. In vitro studies revealed that taurine increased KCC2 inactivation in a phosphorylation-dependent manner. When Thr-906 and Thr-1007 residues in KCC2 were substituted with Ala (KCC2T906A/T1007A), KCC2 activity was facilitated, and the inhibitory effect of taurine was not observed. Exogenous taurine activated the with-no-lysine protein kinase 1 (WNK1) and downstream STE20/SPS1-related proline/alanine-rich kinase (SPAK)/oxidative stress response 1 (OSR1), and overexpression of active WNK1 resulted in KCC2 inhibition in the absence of taurine. Phosphorylation of SPAK was consistently higher in embryonic brains compared with that of neonatal brains and down-regulated by a taurine transporter inhibitor in vivo. Furthermore, cerebral radial migration was perturbed by a taurine-insensitive form of KCC2, KCC2T906A/T1007A, which may be regulated by WNK-SPAK/OSR1 signaling. Thus, taurine and WNK-SPAK/OSR1 signaling may contribute to embryonic neuronal Cl− homeostasis, which is required for normal brain development. PMID:22544747

  17. Effect of taurine supplementation on the alterations in amino Acid content in skeletal muscle with exercise in rat.

    PubMed

    Ishikura, Keisuke; Miyazaki, Teruo; Ra, Song-Gyu; Endo, Shoji; Nakamura, Yusuke; Matsuzaka, Takashi; Miyakawa, Shumpei; Ohmori, Hajime

    2011-01-01

    Taurine included abundantly in skeletal muscle, particularly in the slow-twitch fibers, enhances exercise performance. However, the exact mechanisms for this effect have been unclear. The present study investigated the influence of taurine supplementation on amino acids profile in skeletal muscles as one of mechanisms in the enhancement of exercise performance induced by taurine. In the rats that received taurine solution, amino acids concentrations were comprehensively quantified in two portions with different fiber compositions in the fast-twitch fiber dominant (FFD) gastrocnemius muscle after 2 weeks, and in the gastrocnemius and additional other FFD muscles, liver, and plasma with exhausted exercise after 3 weeks. In the FFD muscles after 2 weeks, a common phenomenon that decreased concentrations of threonine (-16%), serine (-15~-16%), and glycine (-6~-16%) were observed, and they are categorized in the pyruvate precursors for hepatic gluconeogenesis rather than biosynthesis, polar, and side-chain structures. The decreases in the three amino acids were significantly emphasized after an additional week of taurine supplementation in the FFD muscles (p values in three amino acids in these tissues were less than 0.001-0.05), but not in the liver and plasma, accompanied with significantly increase of running time to exhaustion (p <0.05). In contrast, the three amino acids (threonine and serine; p < 0.05, glycine; p < 0.01) and alanine (p < 0.01) in the liver were significantly decreased and increased, respectively, following the exhaustive exercise. In conclusion, the taurine-induced reductions of these amino acids in skeletal muscle might be one of the mechanisms which underpin the enhancement of exercise performance by taurine. Key pointsTaurine ingestion significantly decreased certain amino acids in skeletal muscles accompanied with enhanced exercise performance.The decreased amino acids in common were threonine, serine, and glycine, but not alanine; pyruvate

  18. Effect of Taurine Supplementation on the Alterations in Amino Acid Content in Skeletal Muscle with Exercise in Rat

    PubMed Central

    Ishikura, Keisuke; Miyazaki, Teruo; Ra, Song-Gyu; Endo, Shoji; Nakamura, Yusuke; Matsuzaka, Takashi; Miyakawa, Shumpei; Ohmori, Hajime

    2011-01-01

    Taurine included abundantly in skeletal muscle, particularly in the slow-twitch fibers, enhances exercise performance. However, the exact mechanisms for this effect have been unclear. The present study investigated the influence of taurine supplementation on amino acids profile in skeletal muscles as one of mechanisms in the enhancement of exercise performance induced by taurine. In the rats that received taurine solution, amino acids concentrations were comprehensively quantified in two portions with different fiber compositions in the fast-twitch fiber dominant (FFD) gastrocnemius muscle after 2 weeks, and in the gastrocnemius and additional other FFD muscles, liver, and plasma with exhausted exercise after 3 weeks. In the FFD muscles after 2 weeks, a common phenomenon that decreased concentrations of threonine (-16%), serine (-15~-16%), and glycine (-6~-16%) were observed, and they are categorized in the pyruvate precursors for hepatic gluconeogenesis rather than biosynthesis, polar, and side-chain structures. The decreases in the three amino acids were significantly emphasized after an additional week of taurine supplementation in the FFD muscles (p values in three amino acids in these tissues were less than 0.001-0.05), but not in the liver and plasma, accompanied with significantly increase of running time to exhaustion (p <0.05). In contrast, the three amino acids (threonine and serine; p < 0.05, glycine; p < 0.01) and alanine (p < 0.01) in the liver were significantly decreased and increased, respectively, following the exhaustive exercise. In conclusion, the taurine-induced reductions of these amino acids in skeletal muscle might be one of the mechanisms which underpin the enhancement of exercise performance by taurine. Key points Taurine ingestion significantly decreased certain amino acids in skeletal muscles accompanied with enhanced exercise performance. The decreased amino acids in common were threonine, serine, and glycine, but not alanine; pyruvate

  19. Raman spectra of deuteriated taurine single crystals

    NASA Astrophysics Data System (ADS)

    Souza, J. M. de; Lima, R. J. C.; Freire, P. T. C.; Sasaki, J. M.; Melo, F. E. A.; Filho, J. Mendes; Jones, Derry W.

    2005-05-01

    The polarized Raman spectra of partially deuteriated taurine [(ND 3+) 0.65(NH 3+) 0.35(CH 2) 2SO 3-] crystals from x( zz) x and x( zy) x scattering geometries of the A g and B g irreducible representations of the factor group C 2h are reported. The temperature-dependent Raman spectra of partially deuteriated taurine do not reveal any evidence of the structural phase transition undergone by normal taurine at about 250 K, but an anomaly observed in the 180 cm -1 band at ˜120 K implies a different dynamic for this band (which is involved in a pressure-induced phase transition) in the deuteriated crystal.

  20. Effects of taurine on reperfusion injury.

    PubMed

    Akdemir, Ovunc; Hede, Yan; Zhang, Feng; Lineaweaver, William C; Arslan, Zikri; Songur, Ecmel

    2011-07-01

    Taurine is an organic acid, which has a very important function in the human body. Recently, the antioxidant property of taurine has been much emphasised. In this study, the gracilis muscle flap model was used to investigate the effect of taurine in ischaemia/reperfusion injury in rats. Totally 32 Sprague-Dawley rats were divided into two groups: control group (n = 16) and the treatment group with taurine (n = 16). After elevation of the gracilis muscle flap, 4 h of ischaemia was performed in both groups. Thirty min before the reperfusion, taurine (200 mg kg(-1)) was injected intravenously. After 24 h of reperfusion, the amount of malondialdehyde (MDA), tissue water content and flap viability were evaluated. After 72 h of reperfusion, histological findings were evaluated. Amount of MDA and tissue water content were significantly lower (p < 0.005), and the flap viability was significantly higher (p < 0.005) in the treatment group 24 h after reperfusion. On comparing the outcomes of histological analysis between control and treatment groups, the amounts of collagen, fibroblast and angiogenesis in treatment group were significantly higher than those in the control group. However, the amount of polymorphonuclear leucocyte and tissue necrosis in the treatment group were significantly lower than in the control group. Our results showed that taurine played an important role in the process of ischaemia/reperfusion injury and presented certain protective effects with the improvement in flap survival after ischaemia/reperfusion injury.

  1. Host defense--a role for the amino acid taurine?

    PubMed

    Stapleton, P P; O'Flaherty, L; Redmond, H P; Bouchier-Hayes, D J

    1998-01-01

    Taurine (2-aminoethane sulphonic acid), a ubiquitous beta-amino acid is conditionally essential in man. It is not utilized in protein synthesis but found free or in some simple peptides. Derived from methionine and cysteine metabolism, taurine is known to play a pivotal role in numerous physiological functions. Some of the roles with which taurine has been associated include osmoregulation, antioxidation, detoxification and stimulation of glycolysis and glycogenesis. Intracellular taurine is maintained at high concentrations in a variety of cell types and alteration of cell taurine levels is difficult. The role of taurine within the cell appears to be determined by the cell type. Recent research has determined a regulatory role for taurinechloramine, the product formed by the reaction between taurine and neutrophil derived hypochlorous acid on macrophage function. Plasma taurine levels are also high, although decreases are observed in response to surgical injury and numerous pathological conditions including cancer and sepsis. Supplementary taurine replenishes decreased plasma taurine. Although commonly used as a dietary supplement in the Far East, the potential advantages of dietary taurine supplementation have not as yet been fully recognized in the Western World; this is an area which could prove to be beneficial in the clinical arena.

  2. Protective Effects of S-Adenosylmethionine and Its Combinations With Taurine and/or Betaine Against Lipopolysaccharide or Polyinosinic-polycytidylic Acid-induced Acute Hepatotoxicity

    PubMed Central

    Lee, Seo Yeon; Ko, Kwang Suk

    2016-01-01

    Background Several mechanisms for the pathogenesis of many liver diseases are related with oxidative stress, endotoxins, and infections by many microorganisms. These can lead to chronic hepatitis, cirrhosis, and even liver cancer. The aim of this study was to evaluate the effects of S-adenosylmethionine (SAMe) and its combinations with taurine and/or betaine against hepatotoxicites induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (polyI:C). Methods RAW 264.7 macrophage cells and seven-week-old male C57BL/6 mice were pretreated with SAMe (SAM or AdoMet), taurine, and/or betaine. In order to mimic hepatic injury like endotoxemia or viral infection, cells and mice were treated with LPS or polyI:C. Concentrations of glutathione (GSH), mRNA expressions of GSH synthesizing enzymes, and inflammatory markers were measured by biochemical assays and quantitative real-time PCR. Results In RAW 264.7 cells and mice, pretreatment of SAMe alone or SAMe with taurine and/or betaine attenuated the decrease in GSH levels and mRNA expressions of GSH synthesizing enzymes. In addition, pretreatment of SAMe with taurine and/or betaine prevented the excessive increase in inflammatory mediators produced by LPS or polyI:C treatment. Conclusions Treatment with SAMe in combination with taurine and betaine, would have anti-oxidant functions in addition to anti-inflammatory action against bacterial and/or viral inflammation. PMID:27722141

  3. Relationship between circulating and dietary taurine concentrations in dogs with dilated cardiomyopathy.

    PubMed

    Freeman, L M; Rush, J E; Brown, D J; Roudebush, P

    2001-01-01

    A retrospective study was conducted to determine dietary taurine concentrations in dogs with dilated cardiomyopathy (DCM) and to compare the clinical outcome of taurine-deficient and non-taurine-deficient dogs. Taurine concentrations were low in blood samples from 20 of 37 dogs with DCM. Median dietary taurine concentration was not significantly different between taurine-deficient and nondeficient dogs. There was no correlation between dietary and circulating taurine concentrations. The outcome of taurine-deficient dogs supplemented with taurine was not different from the outcome of nondeficient dogs. The role oftaurine and its relationship to dietary intake in canine DCM remain unclear.

  4. Islet cryopreservation: improved recovery following taurine pretreatment.

    PubMed

    Hardikar, A A; Risbud, M V; Remacle, C; Reusens, B; Hoet, J J; Bhonde, R R

    2001-01-01

    Simple and efficient freezing methods with maximal postthawing recovery form the basis of ideal cryopreservation. Taurine (2-amino ethanesulfonic acid), an end-product of sulphur amino acid metabolism, is one of the most abundant free amino acids in the body. The membrane stabilizing, free radical scavenging, and osmoregulatory roles of taurine have been well documented. We studied the effect of physiological and supra-physiological concentrations (0.3 and 3.0 mM) of taurine on islet cryopreservation. Islet viability on cryopreservation was significantly improved in both the taurine-treated groups (91.9 +/- 2.3% in 0.3 mM and 94.6 +/- 1.58% in 3.0 mM group, p < 0.05) compared with the controls (85.7 +/- 3.4%). Loss of peripheral islet cells was highly reduced in the taurine group, as examined under phase contrast and quantified by islet morphometric analysis (p < 0.05) using a digital image analysis system. Taurine-treated islets showed significant reduction in lipid peroxidation (0.905 and 0.848 nM MDA/microg protein for 0.3 and 3.0 mM taurine, respectively, p < 0.05) compared with control (1.307 nM MDA/microg protein) islets. In all, 500 islet equivalents (IE) of treated or control group islets were transplanted to BALB/c mice rendered diabetic with STZ. All animals showed a normal glucose clearance following a glucose load. Graft functionality was confirmed by normoglycemia (fasting plasma glucose: fpg < 150 mg/dl) after transplantation and reappearing hyperglycemia (fpg > 200 mg/dl) following removal of the graft. Suboptimal islet transplantation using 250 IE suggests that the grafted islet mass was inadequate for diabetes reversal. In addition, no significant differences were observed in the islet insulin content between the three groups following cryopreservation of the islets at -196 degrees C. Our studies indicate that taurine pretreatment and its continued presence during islet cryopreservation improves the postthawing viable recovery of islets.

  5. Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression.

    PubMed

    Clarke, John D; Hardwick, Rhiannon N; Lake, April D; Canet, Mark J; Cherrington, Nathan J

    2014-03-01

    Simvastatin (SIM)-induced myopathy is a dose-dependent adverse drug reaction (ADR) that has been reported to occur in 18.2% of patients receiving a 40- to 80-mg dose. The pharmacokinetics of SIM hydroxy acid (SIMA), the bioactive form of SIM, and the occurrence of SIM-induced myopathy are linked to the function of the organic anion transporting polypeptide (Oatp) hepatic uptake transporters. Genetic polymorphisms in SLCO1B1, the gene for human hepatic OATP1B1, cause decreased elimination of SIMA and increased risk of developing myopathy. Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease, and is known to alter drug transporter expression and drug disposition. The purpose of this study was to assess the metabolism and disposition of SIM in a diet-induced rodent model of NASH. Rats were fed a methionine- and choline-deficient diet for 8 weeks to induce NASH and SIM was administered intravenously. Diet-induced NASH caused increased plasma retention and decreased biliary excretion of SIMA due to decreased protein expression of multiple hepatic Oatps. SIM exhibited increased volume of distribution in NASH as evidenced by increased muscle, decreased plasma, and no change in biliary concentrations. Although Cyp3a and Cyp2c11 proteins were decreased in NASH, no alterations in SIM metabolism were observed. These data, in conjunction with our previous data showing that human NASH causes a coordinated downregulation of hepatic uptake transporters, suggest that NASH-mediated transporter regulation may play a role in altered SIMA disposition and the occurrence of myopathy.

  6. Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts.

    PubMed

    Ramila, K C; Jong, Chian Ju; Pastukh, Viktor; Ito, Takashi; Azuma, Junichi; Schaffer, Stephen W

    2015-02-01

    Taurine is a beta-amino acid found in very high concentration in the heart. Depletion of these intracellular stores results in the development of cardiomyopathy, thought to be mediated by abnormal sarcoplasmic reticular (SR) Ca(2+) transport. There is also evidence that taurine directly alters the Ca(2+) sensitivity of myofibrillar proteins. Major regulators of SR Ca(2+) ATPase (SERCA2a) are the phosphorylation status of a regulatory protein, phospholamban, and SERCA2a expression, which are diminished in the failing heart. The failing heart also exhibits reductions in myofibrillar Ca(2+) sensitivity, a property regulated by the phosphorylation of the muscle protein, troponin I. Therefore, we tested the hypothesis that taurine deficiency leads to alterations in SR Ca(2+) ATPase activity related to reduced phospholamban phosphorylation and expression of SERCA2a. We found that a sequence of events, which included elevated protein phosphatase 1 activity, reduced autophosphorylation of CaMKII, and reduced phospholamban phosphorylation, supports the reduction in SR Ca(2+) ATPase activity. However, the reduction in SR Ca(2+) ATPase activity was not caused by reduced SERCA2a expression. Taurine transporter knockout (TauTKO) hearts also exhibited a rightward shift in the Ca(2+) dependence of the myofibrillar Ca(2+) ATPase, a property that is associated with an elevation in phosphorylated troponin I. The findings support the observation that taurine deficient hearts develop systolic and diastolic defects related to reduced SR Ca(2+) ATPase activity, a change mediated in part by reduced phospholamban phosphorylation. Copyright © 2015 the American Physiological Society.

  7. The effect of taurine on chronic heart failure: actions of taurine against catecholamine and angiotensin II.

    PubMed

    Ito, Takashi; Schaffer, Stephen; Azuma, Junichi

    2014-01-01

    Taurine, a ubiquitous endogenous sulfur-containing amino acid, possesses numerous pharmacological and physiological actions, including antioxidant activity, modulation of calcium homeostasis and antiapoptotic effects. There is mounting evidence supporting the utility of taurine as a pharmacological agent against heart disease, including chronic heart failure (CHF). In the past decade, angiotensin II blockade and β-adrenergic inhibition have served as the mainstay in the treatment of CHF. Both groups of pharmaceutical agents decrease mortality and improve the quality of life, a testament to the critical role of the sympathetic nervous system and the renin--angiotensin system in the development of CHF. Taurine has also attracted attention because it has beneficial actions in CHF, in part by its demonstrated inhibition of the harmful actions of the neurohumoral factors. In this review, we summarize the beneficial actions of taurine in CHF, focusing on its antagonism of the catecholamines and angiotensin II.

  8. Dietary combination of fish oil and taurine decreases fat accumulation and ameliorates blood glucose levels in type 2 diabetic/obese KK-A(y) mice.

    PubMed

    Mikami, Nana; Hosokawa, Masashi; Miyashita, Kazuo

    2012-06-01

    n-3 Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and taurine are functional compounds abundantly present in seafoods. In this study, we examined the combined effects of EPA- and DHA-rich fish oil and taurine on white adipose tissue (WAT) weight and blood glucose levels in diabetic/obese KK-A(y) mice. After a 4-wk administration of experimental diets (soybean oil or fish oil, supplemented with 0%, 2%, or 4% taurine), the increase in WAT weight of the mice fed the "fish oil + 4% taurine" diet was significantly suppressed compared to the "soybean oil + 4% taurine" and "fish oil only" diets. Serum triglycerides, free fatty acids, and total cholesterol levels decreased by fish oil administration. In addition, fish oil and taurine increased the activity of acyl-CoA oxidase, which is the rate-limiting enzyme of peroxisomal β-oxidation, increased in the liver of KK-A(y) mice. The activity of fatty acid synthase decreased by fish oil diets. Furthermore, blood glucose and insulin levels were significantly lower in the mice fed fish oil than in the soybean oil-fed mice. In fish oil + 4% taurine group, hyperglycemia and hyperinsulinemia were effectively improved in KK-A(y) mice compared to the fish oil only groups. In particular, the combination of fish oil and taurine enhanced the glucose transporter 4 (GLUT4) distribution in the plasma membrane of muscle tissue. These results suggest that EPA- and DHA-rich fish oil, especially in combination with taurine, exhibits preventive effects on WAT weight gain and hyperglycemia in diabetic/obese KK-A(y) mice. © 2012 Institute of Food Technologists®

  9. The protective effects of taurine on acute ammonia toxicity in grass carp Ctenopharynodon idellus.

    PubMed

    Xing, Xiaodan; Li, Ming; Yuan, Lixia; Song, Meize; Ren, Qianyan; Shi, Ge; Meng, Fanxing; Wang, Rixin

    2016-09-01

    The four experimental groups were carried out to test the response of grass carp Ctenopharyngodon idella to ammonia toxicity and taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected taurine. Fish in group 2 had the highest ammonia content in the liver and brain, and alanine, arginine, glutamine, glutamate and glycine contents in liver. Brain alanine and glutamate of fish in group 2 were significantly higher than those of fish in group 1. Malondialdehyde content of fish in group 2 was the highest, but superoxide dismutase and glutathione activities were the lowest. Although fish in group 2 had the lowest red cell count and hemoglobin, the highest alkaline phosphatase, complement C3, C4 and total immunoglobulin contents appeared in this group. In addition, superoxide dismutase and glutathione activities, red cell count and hemoglobin of fish in group 3 were significantly higher than those of fish in group 2, but malondialdehyde content is the opposite. This study indicates that ammonia exerts its toxic effects by interfering with amino acid transport, inducing reactive oxygen species generation and malondialdehyde accumulation, leading to blood deterioration and over-activation of immune response. The exogenous taurine could mitigate the adverse effect of high ammonia level on fish physiological disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Acute ammonia toxicity in crucian carp Carassius auratus and effects of taurine on hyperammonemia.

    PubMed

    Ren, Qianyan; Li, Ming; Yuan, Lixia; Song, Meize; Xing, Xiaodan; Shi, Ge; Meng, Fanxing; Wang, Rixin

    2016-12-01

    The four experimental groups were carried out to test the response of crucian carp Carassius auratus to ammonia toxicity and taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected with taurine. Fish in group 2 had the highest ammonia and glutamine contents, and the lowest glutamate content in liver and brain. Serum superoxide dismutase (SOD), glutathione (GSH) activities, red cell count (RBC), white cell count (WBC), lysozyme (LYZ) activity, complement C3 content of fish in group 2 reflected the lowest, but malondialdehyde content was the highest. Importantly, serum SOD and GSH activites, RBC, WBC, and LYZ activity, C3, C4 and total immunoglobulin contents of fish in group 3 were significantly higher than those of fish in group 2. This study indicates that ammonia exerts its toxic effects by interfering with amino acid transport, inducing ROS generation, leading to malondialdehyde accumulation and immunosuppression of crucian carp. The exogenous taurine could mitigate the adverse effect of high ammonia level on fish physiological disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Sulfoacetate released during the assimilation of taurine-nitrogen by Neptuniibacter caesariensis: purification of sulfoacetaldehyde dehydrogenase.

    PubMed

    Krejcík, Zdenĕk; Denger, Karin; Weinitschke, Sonja; Hollemeyer, Klaus; Paces, Václav; Cook, Alasdair M; Smits, Theo H M

    2008-08-01

    Taurine (2-aminoethanesulfonate) is a widespread natural product whose nitrogen moiety was recently shown to be assimilated by bacteria, usually with excretion of an organosulfonate via undefined novel pathways; other data involve transcriptional regulator TauR in taurine metabolism. A screen of genome sequences for TauR with the BLAST algorithm allowed the hypothesis that the marine gammaproteobacterium Neptuniibacter caesariensis MED92 would inducibly assimilate taurine-nitrogen and excrete sulfoacetate. The pathway involved an ABC transporter (TauABC), taurine:pyruvate aminotransferase (Tpa), a novel sulfoacetaldehyde dehydrogenase (SafD) and exporter(s) of sulfoacetate (SafE) (DUF81). Ten candidate genes in two clusters involved three sets of paralogues (for TauR, Tpa and SafE). Inducible Tpa and SafD were detected in cell extracts. SafD was purified 600-fold to homogeneity in two steps. The monomer had a molecular mass of 50 kDa (SDS-PAGE); data from gel filtration chromatography indicated a tetrameric native protein. SafD was specific for sulfoacetaldehyde with a K (m)-value of 0.12 mM. The N-terminal amino acid sequence of SafD confirmed the identity of the safD gene. The eight pathway genes were transcribed inducibly, which indicated expression of the whole hypothetical pathway. We presume that this pathway is one source of sulfoacetate in nature, where this compound is dissimilated by many bacteria.

  12. Review: Taurine: A “very essential” amino acid

    PubMed Central

    Shen, Wen

    2012-01-01

    Taurine is an organic osmolyte involved in cell volume regulation, and provides a substrate for the formation of bile salts. It plays a role in the modulation of intracellular free calcium concentration, and although it is one of the few amino acids not incorporated into proteins, taurine is one of the most abundant amino acids in the brain, retina, muscle tissue, and organs throughout the body. Taurine serves a wide variety of functions in the central nervous system, from development to cytoprotection, and taurine deficiency is associated with cardiomyopathy, renal dysfunction, developmental abnormalities, and severe damage to retinal neurons. All ocular tissues contain taurine, and quantitative analysis of ocular tissue extracts of the rat eye revealed that taurine was the most abundant amino acid in the retina, vitreous, lens, cornea, iris, and ciliary body. In the retina, taurine is critical for photoreceptor development and acts as a cytoprotectant against stress-related neuronal damage and other pathological conditions. Despite its many functional properties, however, the cellular and biochemical mechanisms mediating the actions of taurine are not fully known. Nevertheless, considering its broad distribution, its many cytoprotective attributes, and its functional significance in cell development, nutrition, and survival, taurine is undoubtedly one of the most essential substances in the body. Interestingly, taurine satisfies many of the criteria considered essential for inclusion in the inventory of neurotransmitters, but evidence of a taurine-specific receptor has yet to be identified in the vertebrate nervous system. In this report, we present a broad overview of the functional properties of taurine, some of the consequences of taurine deficiency, and the results of studies in animal models suggesting that taurine may play a therapeutic role in the management of epilepsy and diabetes. PMID:23170060

  13. Role of taurine on acid secretion in the rat stomach.

    PubMed

    Huang, Kai-Han; Chang, Chia-Chieh; Ho, Jau-Der; Lu, Ruey-Hwa; Tsai, Li Hsueh

    2011-02-05

    Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphate) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p < 0.001) of taurine concentrations with cAMP was observed. Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

  14. Role of taurine on acid secretion in the rat stomach

    PubMed Central

    2011-01-01

    Background Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. Methods The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. Results We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphat) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p < 0.001) of taurine concentrations with cAMP was observed. Conclusions Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach. PMID:21294907

  15. Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

    PubMed Central

    Nizamutdinov, Damir; DeMorrow, Sharon; McMillin, Matthew; Kain, Jessica; Mukherjee, Sanjib; Zeitouni, Suzanne; Frampton, Gabriel; Bricker, Paul Clint S.; Hurst, Jacob; Shapiro, Lee A.

    2017-01-01

    Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action. PMID:28106051

  16. The effects of systemically administered taurine and N-pivaloyltaurine on striatal extracellular dopamine and taurine in freely moving rats.

    PubMed

    Salimäki, J; Scriba, G; Piepponen, T P; Rautolahti, N; Ahtee, L

    2003-08-01

    The second most abundant cerebral amino acid, taurine, is widely consumed in the so-called "energy drinks". Therefore, its possible actions on the brain are of great interest. In the present experiments taurine was given intraperitoneally to rats in order to study if it can be administered systemically in large enough amounts to alter cerebral dopaminergic transmission or to induce hypothermia. In addition, the effects of subcutaneously administered lipophilic taurine analogue, N-pivaloyltaurine, were studied. The extracellular striatal taurine and dopamine concentrations were estimated using in vivo microdialysis in awake and freely moving rats, and the rectal temperatures were measured. Taurine at the total dose of 45 mmol/kg i.p. led to a maximally 8-fold increased striatal extracellular taurine concentration, induced a long-lasting hypothermia, and significantly reduced the striatal extracellular dopamine concentration. The latter effect was strengthened by co-treatment with reuptake inhibitor nomifensine. N-pivaloyltaurine (15 mmol/kg in total, s.c.) only slightly elevated the striatal extracellular taurine concentration, failed to alter the rectal temperature, and in contrast to taurine somewhat elevated the striatal extracellular dopamine concentration suggesting a different mechanism or locus of action from that of taurine. Finally, our experiments using brain microdialysis confirmed the earlier findings that taurine is slowly eliminated from the brain. The results clearly indicate that systemically given taurine enters the brain in concentrations that induce pharmacological effects.

  17. Convection and hemoglobin-based oxygen carrier enhanced oxygen transport in a hepatic hollow fiber bioreactor.

    PubMed

    Sullivan, Jesse P; Harris, David R; Palmer, Andre F

    2008-01-01

    Hepatic hollow fiber bioreactors are a promising class of bioartificial liver assist device (BLAD). The development of this type of device is currently hindered by limited oxygen transport to cultured hepatocytes, due to low solubility of oxygen in aqueous media. In order to increase the oxygen spectrum to cultured hepatocytes housed within a hollow fiber bioreactor, several different engineering strategies were explored in this study. These included: supplementing the circulating media stream of the hollow fiber bioreactor with a hemoglobin-based oxygen carrier (bovine red blood cells) with defined oxygen binding and release kinetics and operating the bioreactor with media flow through the hollow fiber membrane into the extracapillary space (ECS). We hypothesize that these two strategies can be used to improve hepatocyte oxygenation and possibly attain an in vivo-like pO(2) spectrum, similar to that observed in vivo in the liver sinusoid. This work is significant, since provision of an in vivo-like pO(2) spectrum should create a fully functional BLAD that could potentially bridge thousands of liver failure patients towards native liver regeneration of damaged tissue or, if necessary, orthotopic liver transplantation.

  18. Reduced serotonin reuptake transporter (SERT) function causes insulin resistance and hepatic steatosis independent of food intake.

    PubMed

    Chen, Xiaoning; Margolis, Kara J; Gershon, Michael D; Schwartz, Gary J; Sze, Ji Y

    2012-01-01

    Serotonin reuptake transporter (SERT) is a key regulator of serotonin neurotransmission and a major target of antidepressants. Antidepressants, such as selectively serotonin reuptake inhibitors (SSRIs), that block SERT function are known to affect food intake and body weight. Here, we provide genetic evidence that food intake and metabolism are regulated by separable mechanisms of SERT function. SERT-deficient mice ate less during both normal diet and high fat diet feeding. The reduced food intake was accompanied with markedly elevated plasma leptin levels. Despite reduced food intake, SERT-deficient mice exhibited glucose intolerance and insulin resistance, and progressively developed obesity and hepatic steatosis. Several lines of evidence indicate that the metabolic deficits of SERT-deficient mice are attributable to reduced insulin-sensitivity in peripheral tissues. First, SERT-deficient mice exhibited beta-cell hyperplasia and islet-mass expansion. Second, biochemical analyses revealed constitutively elevated JNK activity and diminished insulin-induced AKT activation in the liver of SERT-deficient mice. SERT-deficient mice exhibited hyper-JNK activity and hyperinsulinemia prior to the development of obesity. Third, enhancing AKT signaling by PTEN deficiency corrected glucose tolerance in SERT-deficient mice. These findings have potential implications for designing selective SERT drugs for weight control and the treatment of metabolic syndromes.

  19. Organic anion-transporting polypeptides contribute to the hepatic uptake of berberine.

    PubMed

    Chen, Chen; Wu, Zhi-Tao; Ma, Lei-Lei; Ni, Xuan; Lin, Yun-Fei; Wang, Le; Chen, Ke-Ping; Huang, Cheng-gang; Pan, Guoyu

    2015-01-01

    1. The purpose of this study was to investigate the mechanism of hepatic uptake of berberine. Berberine accumulation in hepatocytes was found to be highly dependent on active uptake, which could not be explained by liver organic cation transporter (OCT) alone. 2. Our studies indicated that berberine uptake was significantly suppressed by rifampicin, cyclosporine A and glycyrrhizic acid, which act as specific inhibitors of different Oatp isoforms (Oatp1a1, Oatp1a4 and Oatp1b2) in rat hepatocytes. The combination of OCT and OATP inhibitors further reduced berberine accumulation in both rat and human hepatocytes. The uptake of berberine could be increased in human HEK293-OATP1B3 but not in OATP1B1-transfected HEK 293 cells. 3. Rifampicin could reduce the berberine liver extraction ratio (ER) and double its concentration in the effluent in isolated rat livers. Further in vivo study indicated that berberine plasma exposure could be significantly increased by co-administration of the OATP inhibitor rifampicin or the substrate rosuvastatin. 4. In conclusion, this study demonstrated that both OCT and OATP contribute to the accumulation of berberine in the liver. OATPs may have important roles in berberine liver disposition and potential clinically relevant drug--drug interactions.

  20. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive...

  1. OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin

    PubMed Central

    Chen, Ligong; Shu, Yan; Liang, Xiaomin; Chen, Eugene C.; Yee, Sook Wah; Zur, Arik A.; Li, Shuanglian; Xu, Lu; Keshari, Kayvan R.; Lin, Michael J.; Chien, Huan-Chieh; Zhang, Youcai; Morrissey, Kari M.; Liu, Jason; Ostrem, Jonathan; Younger, Noah S.; Kurhanewicz, John; Shokat, Kevan M.; Ashrafi, Kaveh; Giacomini, Kathleen M.

    2014-01-01

    Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug. However, its endogenous role is poorly understood. Here we show that similar to metformin treatment, loss of Oct1 caused an increase in the ratio of AMP to ATP, activated the energy sensor AMP-activated kinase (AMPK), and substantially reduced triglyceride (TG) levels in livers from healthy and leptin-deficient mice. Conversely, livers of human OCT1 transgenic mice fed high-fat diets were enlarged with high TG levels. Metabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1. Thiamine deficiency enhanced the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase. Metformin and the biguanide analog, phenformin, competitively inhibited OCT1-mediated thiamine uptake. Acute administration of metformin to wild-type mice reduced intestinal accumulation of thiamine. These findings suggest that OCT1 plays a role in hepatic steatosis through modulation of energy status. The studies implicate OCT1 as well as metformin in thiamine disposition, suggesting an intriguing and parallel mechanism for metformin and its major hepatic transporter in metabolic function. PMID:24961373

  2. Role of taurine in the pathogenesis of obesity.

    PubMed

    Murakami, Shigeru

    2015-07-01

    Taurine is a sulfur-containing amino acid that is present in mammalian tissues in millimolar concentrations. Taurine is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. The prevalence of obesity and being overweight continues to rise worldwide at an alarming rate. Obesity is associated with a higher risk of metabolic and cardiovascular diseases, cancer, and other clinical conditions. Ingestion of taurine has been shown to alleviate metabolic diseases such as hyperlipidemia, diabetes, hypertension, and obesity in animal models. A global epidemiological survey showed that 24-h urinary taurine excretion, as a marker of dietary taurine intake, was inversely associated with BMI, blood pressure, and plasma cholesterol in humans. In addition, taurine chloramine, an endogenous product derived from activated neutrophils, has been reported to suppress obesity-induced oxidative stress and inflammation in adipocytes. Synthetic activity and concentration of taurine in adipose tissues and plasma have been shown to decrease in humans and animals during the development of obesity, suggesting a relationship between taurine deficiency and obesity. In this review, I summarize the effects of taurine on the progression of obesity in animal models and humans. Furthermore, I discuss possible mechanisms underlying the antiobesity effects of taurine. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Taurine attenuates cold ischemia-reoxygenation injury in rat liver.

    PubMed

    Wettstein, M; Häussinger, D

    2000-06-15

    Taurine, betaine, and inositol were recently identified as osmolytes in liver cells interfering with cell volume regulation and cell function. In this study, the effect of osmolytes on cold ischemia-reoxygenation injury was investigated in rat liver. Isolated rat livers were flushed for 15 min with Krebs-Henseleit buffer (KHB), then stored for 16 hr in KHB at 4 degrees C, and thereafter reperfused with oxygenated KHB for 180 min. When taurine, betaine, and inositol (2 mmol/L, each) were added to the preperfusion and storage buffer, lactate dehydrogenase, aspartate amino transferase, and glutathione S-transferase leakage into the effluent perfusate during the reoxygenation period were less than half compared to controls without osmolytes and bile flow was higher. The effect of taurine (2 mmol/L) was similar to a mixture of all three osmolytes, indicating that taurine is the most important constituent. When livers were stored for 24 hr in University of Wisconsin solution, osmolyte addition to the storage solution also decreased lactate dehydrogenase and aspartate aminotransferase leakage during reoxygenation. Increasing liver taurine content by a 7-day taurine supplementation of drinking water attenuated reoxygenation injury in cold and warm ischemia in rat livers, whereas taurine depletion by beta-alanine feeding had the opposite effect. The data show that taurine protects livers from ischemia-reoxygenation. Taurine addition to perfusion and storage solutions in low millimolar concentrations or taurine supplementation of the donor may be useful to protect transplanted organs.

  4. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    PubMed Central

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  5. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    PubMed

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

  6. No beneficial effects of taurine application on oxygen free radical production after hemorrhagic shock in rats.

    PubMed

    Niessen, F; Isselhard, W; Minor, T

    1998-01-01

    Oxygen free radical generation contributes to the reinfusion damage after hemorrhagic shock. Taurine has been proposed to have radical scavenging properties under certain experimental conditions. Therefore the present study was undertaken to investigate if taurine would be able to attenuate adverse effects of shock/resuscitation in male rats (fasted over night). Under pentobarbital anesthesia, hemorrhagic shock (HS) was induced for 1 h by bleeding of the animal [mean arterial blood pressure (MAP) = 40 mm Hg] followed by shed blood reinfusion and another 1 h period of resuscitation. Rats were divided into two groups: Treated rats (n = 6) were injected with taurine (40 mg/kg body mass) prior to withdrawal of shed blood; untreated rats (n = 9) received respective volumes of a normal saline solution. In untreated animals, free radical induced lipid peroxidation was documented by an increase of malondialdehyde (MDA) in the systemic circulation (nmol/ml; HPLC measurement) from 1.06 +/- 0.08 during normotension (NT) to 1.35+/- 0.18** 1 h after resuscitation (RS). Accordingly, plasma levels of alanine aminotransferase (ALT) (11 +/- 2; 35 +/- 12; 94 +/- 44 U/l, NT; HS; RS) and ammonia (120 +/- 39; 532 +/- 161; 224 +/- 101 micrograms/dl) changed significantly during the experimental protocol. Hepatic ATPase-content as an indicator of energetic status of the liver fell from 4.8 +/- 0.83 to 0.56 +/- 0.27 after HS and recovered to only 2.7 +/- 1.6 mumol/g after RS. Leukocyte infiltration of the liver was followed by tissue levels of myeloperoxidase (MPO) which did not change during HS, but rose during RS (37.9 +/- 18.5; 38.6 +/- 16.4; 77.5 +/- 24; arbitrary units), documenting an inflammatory reaction after HS. Taurine treated rats showed levels of MDA not different from untreated rats after RS; also no differences were observed concerning enzyme concentrations and ammonia levels. The liver tissue levels of ATP and MPO revealed no differences between the two groups during the

  7. Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice.

    PubMed

    Cui, Xuezhi; Navneet, Soumya; Wang, Jing; Roon, Penny; Chen, Wei; Xian, Ming; Smith, Sylvia B

    2017-04-01

    Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/-]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/-]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also. Retinas isolated from wild-type (WT), Mthfr+/-, and Cbs+/- mice (12 and 22 weeks) were analyzed for methylene tetrahydrofolate reductase (MTHFR), cystathionine-β-synthase (CBS), and cystathionase (CTH) RNA/protein levels. Retinas were evaluated for levels of reduced:oxidized GSH (GSH:GSSG), Slc7a11 (xCT), taurine, taurine transporter (TAUT), and H2S. Aside from decreased CBS RNA/protein levels in Cbs+/- retinas, there were minimal alterations in remethylation/transsulfuration pathways in the two mutant mice strains. Glutathione and taurine levels in Mthfr+/- and Cbs+/- retinas were similar to WT, which may be due to robust levels of xCT and TAUT in mutant retinas. Interestingly, levels of H2S were markedly increased in retinas of Mthfr+/- and Cbs+/- mice compared with WT. Ganglion cell loss and vasculopathy observed in Mthfr+/- and Cbs+/- mouse retinas may be milder than expected, not because of compensatory increases of enzymes in remethylation/transsulfuration pathways, but because downstream transsulfuration pathway products GSH, taurine, and H2S are maintained at robust levels. Elevation of H2S is particularly intriguing owing to neuroprotective properties reported for this gasotransmitter.

  8. Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice

    PubMed Central

    Cui, Xuezhi; Navneet, Soumya; Wang, Jing; Roon, Penny; Chen, Wei; Xian, Ming; Smith, Sylvia B.

    2017-01-01

    Purpose Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/−]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/−]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also. Methods Retinas isolated from wild-type (WT), Mthfr+/−, and Cbs+/− mice (12 and 22 weeks) were analyzed for methylene tetrahydrofolate reductase (MTHFR), cystathionine-β-synthase (CBS), and cystathionase (CTH) RNA/protein levels. Retinas were evaluated for levels of reduced:oxidized GSH (GSH:GSSG), Slc7a11 (xCT), taurine, taurine transporter (TAUT), and H2S. Results Aside from decreased CBS RNA/protein levels in Cbs+/− retinas, there were minimal alterations in remethylation/transsulfuration pathways in the two mutant mice strains. Glutathione and taurine levels in Mthfr+/− and Cbs+/− retinas were similar to WT, which may be due to robust levels of xCT and TAUT in mutant retinas. Interestingly, levels of H2S were markedly increased in retinas of Mthfr+/− and Cbs+/− mice compared with WT. Conclusions Ganglion cell loss and vasculopathy observed in Mthfr+/− and Cbs+/− mouse retinas may be milder than expected, not because of compensatory increases of enzymes in remethylation/transsulfuration pathways, but because downstream transsulfuration pathway products GSH, taurine, and H2S are maintained at robust levels. Elevation of H2S is particularly intriguing owing to neuroprotective properties reported for this gasotransmitter. PMID:28384716

  9. Beta-alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro.

    PubMed

    Mori, Masahiro; Gähwiler, Beat H; Gerber, Urs

    2002-02-15

    Electrophysiological and pharmacological properties of glycine receptors were characterized in hippocampal organotypic slice cultures. In the presence of ionotropic glutamate and GABA(B) receptor antagonists, pressure-application of glycine onto CA3 pyramidal cells induced a current associated with increased chloride conductance, which was inhibited by strychnine. Similar chloride currents could also be induced with beta-alanine or taurine. Whole-cell glycine responses were significantly greater in CA3 pyramidal cells than in CA1 pyramidal cells and dentate granule cells, while responses to GABA were similar among these three cell types. Although these results demonstrate the presence of functional glycine receptors in the hippocampus, no evidence for their activation during synaptic stimulation was found. Gabazine, a selective GABA(A) receptor antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells. Glycine receptor activation is not dependent on transporter-controlled levels of extracellular glycine, as no chloride current was observed in response to sarcosine, an inhibitor of glycine transporters. In contrast, application of guanidinoethanesulfonic acid, an uptake inhibitor of beta-alanine and taurine, induced strychnine-sensitive chloride current in the presence of gabazine. These data indicate that modulation of transporters for the endogenous amino acids, beta-alanine and taurine, can regulate tonic activation of glycine receptors, which may function in maintenance of inhibitory tone in the hippocampus.

  10. Diet and biosynthesis as sources of taurine in the mouse.

    PubMed

    Huxtable, R J; Lippincott, S E

    1982-05-01

    The quantitative importance of diet versus biosynthesis as sources of taurine has been established in mice receiving dietary levels of 0.062% [3H]taurine and 0.74% [35S]methionine as sole sulfur-containing amino acids. After 15 days on diets radiolabeled with these levels of taurine and methionine, 16% of total-body taurine had been derived from diet and 24% from biosynthesis. By 30 days, these contributions had risen to 29% and 33%, respectively, and by 61 days to 46%. The half-life of turnover of taurine in the mouse was 18.6 days. These findings indicate that, like the rat and guinea pig, but unlike the cat and human, the mouse exhibits considerable biosynthetic capacity for taurine.

  11. Taurine regulation of voltage-gated channels in retinal neurons.

    PubMed

    Rowan, Matthew J M; Bulley, Simon; Purpura, Lauren A; Ripps, Harris; Shen, Wen

    2013-01-01

    Taurine activates not only Cl(-)-permeable ionotropic receptors but also receptors that mediate metabotropic responses. The metabotropic property of taurine was revealed in electrophysiological recordings obtained after fully blocking Cl(-)-permeable receptors with an inhibitory "cocktail" consisting of picrotoxin, SR95531, and strychnine. We found that taurine's metabotropic effects regulate voltage-gated channels in retinal neurons. After applying the inhibitory cocktail, taurine enhanced delayed outward rectifier K(+) channels preferentially in Off-bipolar cells, and the effect was completely blocked by the specific PKC inhibitor, GF109203X. Additionally, taurine also acted through a metabotropic pathway to suppress both L- and N-type Ca(2+) channels in retinal neurons, which were insensitive to the potent GABA(B) receptor inhibitor, CGP55845. This study reinforces our previous finding that taurine in physiological concentrations produces a multiplicity of metabotropic effects that precisely govern the integration of signals being transmitted from the retina to the brain.

  12. 33S NMR cryogenic probe for taurine detection

    NASA Astrophysics Data System (ADS)

    Hobo, Fumio; Takahashi, Masato; Maeda, Hideaki

    2009-03-01

    With the goal of a S33 nuclear magnetic resonance (NMR) probe applicable to in vivo NMR on taurine-biological samples, we have developed the S33 NMR cryogenic probe, which is applicable to taurine solutions. The NMR sensitivity gain relative to a conventional broadband probe is as large as 3.5. This work suggests that improvements in the preamplifier could allow NMR measurements on 100 μM taurine solutions, which is the level of sensitivity necessary for biological samples.

  13. [Taurine and carnosine in tissues of Pacific mollusks].

    PubMed

    Aiushin, N B; Petrova, I Iu; Epshteĭn, L M

    1997-01-01

    The containing of taurine and carnosine (low-molecular biologically active substances) was studied in tissues of molluscs (Gastropodae, Brahiopodae and Cephalopodae) by 38 species. The highest concentration of taurine found in the octopus and 5 species of shells (Gastropodae). The containing of carnosine in mollusks is highly lower than in bovine muscles. Organoleptic quality of lyophilized water-spirit extracts by soft tissues of molluscs allow to use it as a taurine-enriching food addition.

  14. Taurine and ethanol interactions: behavioral effects in mice

    PubMed Central

    Ginsburg, Brett C.; Lamb, Richard J.

    2011-01-01

    Taurine is an abundant amino acid in the brain that shares pharmacological effects and similar potency with ethanol. Recently, taurine-containing beverages have been reported to enhance the euphoric effects of ethanol, though the extent of this effect and the role of taurine remain speculative. The present study was designed to explore interactions between taurine and ethanol on several behaviors including locomotion, ataxia, and loss of righting. Two strains of mice, C57BL/6J and DBA/2J mice, were used to examine potential strain differences. In the first experiment, effects of various doses of taurine (0.3–3.0 g/kg), ethanol (1.0–4.2 g/kg), or taurine in combination with ethanol were assessed in a within-subjects design. Although taurine did not appear to alter effects of ethanol on any measure in either strain, the development of tolerance to locomotor effects and sensitization to ataxic effects of ethanol in DBA/2J mice complicated interpretation of these results. In a second experiment, drug-naïve mice were assigned to one of four treatment groups: saline + saline, saline + ethanol (1.78 g/kg), taurine (1.78 g/kg) + saline, or ethanol + taurine. In this experiment, taurine pretreatment significantly attenuated the locomotor-stimulating effect of ethanol in both strains (but to a greater extent in C57BL/6J mice) and appeared to reduce the ataxic effects of ethanol in C57BL/6J mice. In conclusion, the interaction between taurine and ethanol is subtle. Further, results are inconsistent with the notion that taurine plays a major role in the locomotor, ataxic, or loss of righting effects of ethanol. PMID:17961547

  15. The potential protective role of taurine against experimental allergic inflammation.

    PubMed

    Nam, Sun-Young; Kim, Hyung-Min; Jeong, Hyun-Ja

    2017-09-01

    Taurine has been widely evaluated as a potential therapeutic agent in chronic inflammatory disorders and various infections. However, the potential role of taurine in regulating allergic inflammatory responses is currently unknown. The present study was designed to evaluate the in vitro effects of taurine on the levels of thymic stromal lymphopoietin (TSLP) and other pro-inflammatory cytokines and activation of caspase-1 and nuclear factor (NF)-κB as well as the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-triggered human mast cell line, HMC-1 cells. Furthermore, we assessed the therapeutic effects of taurine on ovalbumin (OVA)-induced allergic rhinitis (AR) animal models. Here, the obtained results showed that taurine dose-dependently inhibited the production and mRNA expression of TSLP and pro-inflammatory cytokines in HMC-1 cells exposed to PMACI. Taurine attenuated the phosphorylation of JNK and p38 in activated HMC-1 cells. Moreover, taurine brought a significant inhibition of the activities of NF-κB and caspase-1. In an OVA-induced AR animal model, the increased levels of nose rubbing, histamine, immunoglobulin E, TSLP, and interleukin IL-1β were dramatically reduced by the administration of taurine. In summary, taurine could serve as potential novel remedy of allergic inflammatory disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Ethanol enhances taurine-activated glycine receptor function

    PubMed Central

    Welsh, Brian T.; Kirson, Dean; Allen, Hunter M.; Mihic, S. John

    2010-01-01

    Background Emerging evidence suggests that taurine acts as a partial agonist at glycine receptors (GlyR) in vitro and in vivo. Ethanol acts as an allosteric modulator at the GlyR producing a leftward shift of the glycine concentration-response curve, with no enhancing effects observed at saturating glycine concentrations. However, to date no electrophysiological studies have been performed on ethanol modulation of taurine-activated GlyR. Methods Wildtype α1 GlyR, or those bearing a serine-267 to isoleucine replacement (S267I), were homomerically expressed in Xenopus oocytes and voltage-clamped at 70 mV. Ethanol was co-applied with varying concentrations of glycine or taurine and the enhancing effects of ethanol compared. Results Ethanol potentiated glycine- and taurine-activated GlyR responses in a concentration-dependent manner. It shifted taurine and glycine concentration-response curves to the left, having no effects at saturating agonist concentrations. Chelation of zinc by tricine decreased ethanol enhancement of taurine-gated GlyR function. The S267I mutation prevented ethanol enhancement of taurine-mediated responses as previously also reported for glycine. Conclusion Ethanol modulates taurine activation of GlyR function by a mechanism similar to that of the full agonist glycine. The lack of effect of ethanol at saturating taurine concentrations provides mechanistic information on alcohol actions at the GlyR. PMID:20586750

  17. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex.

    PubMed

    Furukawa, Tomonori; Yamada, Junko; Akita, Tenpei; Matsushima, Yoshitaka; Yanagawa, Yuchio; Fukuda, Atsuo

    2014-01-01

    γ-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67(GFP/GFP)) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose-response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAAR blockade in GAD67(GFP/GFP) mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the developing neocortex.

  18. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex

    PubMed Central

    Furukawa, Tomonori; Yamada, Junko; Akita, Tenpei; Matsushima, Yoshitaka; Yanagawa, Yuchio; Fukuda, Atsuo

    2014-01-01

    γ-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67GFP/GFP) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose–response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAAR blockade in GAD67GFP/GFP mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the developing neocortex. PMID:24734001

  19. Nrf2- and PPARα-Mediated Regulation of Hepatic Mrp Transporters after Exposure to Perfluorooctanoic Acid and Perfluorodecanoic Acid

    PubMed Central

    Maher, Jonathan M.; Aleksunes, Lauren M.; Dieter, Matthew Z.; Tanaka, Yuji; Peters, Jeffrey M.; Manautou, Jose E.; Klaassen, Curtis D.

    2008-01-01

    Perfluorooctanoic acid and perfluorodecanoic acid (PFDA) are commonly used as emulsifiers and surfactants in fluoropolymer manufacturing and are known peroxisome proliferator–activated receptor alpha (PPARα) agonists. PPARα activation induces β- and ω-oxidation enzymes such as Cyp4a14 and acyl-CoA oxidase, which are a likely cause of subsequent oxidative stress and peroxisome proliferation. Conversely, NF-E2-related factor-2 (Nrf2) is a transcription factor that protects against oxidative stress and inflammation by regulating several detoxification and xenobiotic transporter genes. Because PFDA markedly induces hepatic metabolism and oxidative stress, we hypothesized that PFDA exposure would increase expression of hepatic efflux multidrug resistance–associated protein (Mrp) transporters. A single PFDA dose (80 mg/kg) administered to mice increased hepatic Mrp3 (fourfold) and Mrp4 (31-fold) mRNA expression. Upregulation of Mrp3 and Mrp4 correlated with elevated serum-conjugated bilirubin and bile acids, respectively. To determine the mechanism of Mrp3 and Mrp4 induction, PFDA was administered to Nrf2-null mice, PPARα-null mice, and mice pretreated with gadolinium chloride, a Kupffer cell–depleting chemical capable of inhibiting the inflammatory cytokine response. In both PPARα- and Nrf2-null mice, maximal induction of Mrp3 and Mrp4 mRNA after PFDA administration was attenuated. Gadolinium chloride pretreatment reduced serum and hepatic tumor necrosis factor-α levels after PFDA treatment, as well as Mrp4 mRNA expression by 30%, suggesting that Kupffer cell–derived mediators may contribute to Mrp induction. Thus, after PFDA administration, the liver mounts a compensatory hepatoprotective response via PPARα and Nrf2, markedly increasing Mrp3 and Mrp4 expression, with corresponding increases in serum of known Mrp3 and Mrp4 substrates. PMID:18757529

  20. Amino acid residues involved in the substrate specificity of TauT/SLC6A6 for taurine and γ-aminobutyric acid.

    PubMed

    Yahara, Tohru; Tachikawa, Masanori; Akanuma, Shin-ichi; Kubo, Yoshiyuki; Hosoya, Ken-ichi

    2014-01-01

    Taurine transporter (TauT/SLC6A6) is an "honorary" γ-aminobutyric acid (GABA) transporter because of its low affinity for GABA. The sequence analysis of TauT implied the role of Gly57, Phe58, Leu306 and Glu406 in the substrate recognition of TauT, and amino acid-substitutions were performed. Immunocytochemistry supported no marked effect of mutations on the expression of TauT. TauT-expressing oocytes showed a reduction in [(3)H]taurine uptake by G57E, F58I, L306Q and E406C, and change in [(3)H]GABA uptake by G57E and E406C, suggesting their significant roles in the function of TauT. G57E lost the activity of [(3)H]taurine and [(3)H]GABA uptake, suggesting that Gly57 is involved in the determination of substrate pocket volume and in the interaction with substrates. E406C exhibited a decrease and an increase in the affinity for taurine and GABA, respectively, suggesting the involvement of Glu406 in the substrate specificity of TauT. The inhibition study supported the role of Glu406 in the substrate specificity since [(3)H]taurine and [(3)H]GABA uptake by E406C was less sensitive to taurine and β-alanine, and more sensitive to GABA and nipecotic acid than was the case with wild type of TauT. F58I had an increased affinity for GABA, suggesting the involvement of Phe58 in the substrate accessibility. The kinetic parameters showed the decreased and increased affinities of L306Q for taurine and GABA, respectively, supporting that substrate recognition of TauT is conformationally regulated by the branched-side chain of Leu306. In conclusion, the present results suggest that these residues play important roles in the transport function and substrate specificity of TauT.

  1. Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy.

    PubMed

    Terrill, Jessica R; Pinniger, Gavin J; Graves, Jamie A; Grounds, Miranda D; Arthur, Peter G

    2016-06-01

    Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis. Cysteine precursor antioxidants such as N-acetyl cysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine. We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress. Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug. These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l-2-oxothiazolidine-4-carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex

  2. Stress- (and diet-) related regulation of hepatic nuclear receptors and its relevance for ABC-transporter functions.

    PubMed

    Stienstra, Rinke; Lichtenauer-Kaligis, Elgin; Müller, Michael

    2004-05-01

    Nuclear receptors (NRs) play an important role in maintaining cellular homeostasis. With clearly established roles in fatty acid metabolism and inflammation, peroxisome proliferator activated receptors (PPARs) and other nuclear receptors are essential in liver functioning. However, much less is known about the regulation of NRs themselves during inflammatory processes in the liver. Interestingly PPARs and other NRs are negative acute phase proteins because they become rapidly downregulated during the acute phase response. However, PPARs have important roles in modulating inflammatory responses. One of the mechanisms by which dietary or inflammatory stress is relieved involves the hepatic adenosine triphosphate-binding cassette (ABC) transporter proteins, which import and export a wide variety of substrates. These ABC transporters are under close control of several NRs. Because NRs play important roles in fatty acid metabolism and inflammation as well as in the regulation of bile production, they are reviewed here with respect to their role in dietary and stress-related responses of the liver and their impact on the regulation and function of hepatic ABC transporters.

  3. Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug–Drug Interactions

    PubMed Central

    2012-01-01

    The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug–drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors. PMID:22541068

  4. Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.

    PubMed

    Karlgren, Maria; Vildhede, Anna; Norinder, Ulf; Wisniewski, Jacek R; Kimoto, Emi; Lai, Yurong; Haglund, Ulf; Artursson, Per

    2012-05-24

    The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.

  5. Taurine inhibition of metal-stimulated catecholamine oxidation.

    PubMed

    Dawson, R; Baker, D; Eppler, B; Tang, E; Shih, D; Hern, H; Hu, M

    2000-01-01

    Taurine is an abundant amino acid found in mammalian tissues and it has been suggested to have cytoprotective functions. The aim of the present study was to determine if taurine had the potential to reduce oxidative stress associated with metal-stimulated catecholamine oxidation. Taurine and structural analogs of taurine were tested for their ability to inhibit metal-stimulated quinone formation from dopamine or L-dopa. Oxidative damage to proteins and lipids were also assessed in vitro and the effects of taurine were determined. Taurine (20 mM) was found to decrease significantly ferric iron (50-500 microM)- and manganese (10 microM)-stimulated L-dopa or dopamine oxidation. Taurine had no effect on zinc-induced dopamine oxidation and slightly potentiated copper- and NaIO(4)-stimulated quinone formation. Ferric iron-stimulated lipid peroxidation was not affected by taurine (1-20 mM). Protein carbonyl formation induced by ferric iron (500 microM) and L-dopa (500 microM) was significantly reduced by 10 mM taurine. The cytotoxicity of L-dopa (250 microM) and ferric chloride (75 microM) to LLC-PK(1) cells was attenuated by 10 mM taurine or hypotaurine. Homotaurine alone stimulated L-dopa oxidation and potentiated the cytotoxic effects of ferric iron. Homotaurine was found to be cytotoxic when combined with L-dopa or L-dopa/iron. In contrast, hypotaurine inhibited quinone formation and protected LLC-PK(1) cells. These studies suggest that taurine may exhibit cytoprotective effects against the oxidation products of catecholamines by acting as a scavenger for free radicals and cytotoxic quinones.

  6. Inhibitory effect of taurine on veratridine-evoked D-[3H]aspartate release from murine corticostriatal slices: involvement of chloride channels and mitochondria.

    PubMed

    Molchanova, Svetlana M; Oja, Simo S; Saransaari, Pirjo

    2007-01-26

    We have previously shown that the inhibitory neuromodulator taurine attenuates the release of preloaded D-[3H]aspartate from murine corticostriatal slices evoked by ischemic conditions or by application of the sodium channel agonist veratridine. The release of D-[3H]aspartate (a non-metabolized analog of glutamate) was used as an index of glutamate release. The aim of the present study was to reveal the molecular mechanisms responsible for this inhibitory effect of taurine. It was shown that 10 mM taurine suppresses D-[3H]aspartate release evoked by 0.1 mM veratridine, but does not affect the high-K+ -(50 mM) or ouabain- (0.1 mM) evoked release. Taurine had no effect in Ca2+ -free medium when the synaptic exocytosis of D-[3H]aspartate was inhibited. Nor did it suppress the release from slices preloaded with the competitive glutamate uptake blocker DL-threo-beta-hydroxyaspartate (THBA), which inhibits D-[3H]aspartate release mediated by the reverse action of glutamate transporters. Omission of Cl- from the incubation medium reduced the effect of taurine, signifying the involvement of a Cl- channel. The glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline did not block the taurine effect, although picrotoxin, a less specific blocker of agonist-gated chloride channels, completely prevented the effect of taurine on veratridine-induced D-[3H]aspartate release. The respiratory chain blocker rotenone or mitochondrial protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in combination with the mitochondrial ATPase inhibitor oligomycin, which inhibits the mitochondrial Ca2+ uniporter, also reduced the effect of taurine. The results obtained in the present study show that taurine acts specifically on the release of preloaded D-[3H]aspartate evoked by veratridine, but not on that evoked by other depolarizing agents, and affects the release mediated both by synaptic exocytosis and the reverse action of glutamate transporter. Taurine

  7. Meta-analysis of expression of hepatic organic anion-transporting polypeptide (OATP) transporters in cellular systems relative to human liver tissue.

    PubMed

    Badée, Justine; Achour, Brahim; Rostami-Hodjegan, Amin; Galetin, Aleksandra

    2015-04-01

    Organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 transporters play an important role in hepatic drug disposition. Recently, an increasing number of studies have reported proteomic expression data for OATP transporters. However, systematic analysis and understanding of the actual differences in OATP expression between liver tissue and commonly used cellular systems is lacking. In the current study, meta-analysis was performed to assess the protein expression of OATP transporters reported in hepatocytes relative to liver tissue and to identify any potential correlations in transporter expression levels in the same individual. OATP1B1 was identified as the most abundant uptake transporter at 5.9 ± 8.3, 5.8 ± 3.3, and 4.2 ± 1.7 fmol/μg protein in liver tissue, sandwich-cultured human hepatocytes (SCHH), and cryopreserved suspended hepatocytes, respectively. The rank order in average expression in liver tissue and cellular systems was OATP1B1 > OATP1B3 ≈ OATP2B1. Abundance levels of the OATP transporters investigated were not significantly different between liver and cellular systems, with the exception of OATP2B1 expression in SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3, and OATP2B1 liver expression data in the same individuals (n = 86) identified weak (OATP1B1-OATP2B1) to moderately (OATP1B3-OATP2B1) significant correlations. A significant weak correlation was noted between OATP1B1 abundance and age of human donors, whereas expression of the OATPs investigated was independent of sex. Implications of the current analysis on the in vitro-in vivo extrapolation of transporter-mediated drug disposition using physiologically based pharmacokinetic models are discussed. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Activation of the aryl hydrocarbon receptor induces hepatic steatosis via the upregulation of fatty acid transport.

    PubMed

    Kawano, Yuki; Nishiumi, Shin; Tanaka, Shinwa; Nobutani, Kentaro; Miki, Akira; Yano, Yoshihiko; Seo, Yasushi; Kutsumi, Hiromu; Ashida, Hitoshi; Azuma, Takeshi; Yoshida, Masaru

    2010-12-15

    The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix/Per-ARNT-Sim domain transcription factor, which is activated by various xenobiotic ligands. AHR is known to be abundant in liver tissue and to be associated with hepatic steatosis. However, it has not yet been elucidated how the activation of AHR promotes hepatic steatosis. The aim of this study is to clarify the role of AHR in hepatic steatosis. The intraperitoneal injection of 3-methylcholanthrene (3MC), a potent AHR ligand, into C57BL/6J mice significantly increased the levels of triglycerides and six long-chain monounsaturated fatty acids in the livers of mice, resulting in hepatic microvesicular steatosis. 3MC significantly enhanced the expression level of fatty acid translocase (FAT), a factor regulating the uptake of long-chain fatty acids into hepatocytes, in the liver. In an in vitro experiment using human hepatoma HepG2 cells, 3MC increased the expression level of FAT, and the downregulation of AHR by AHR siRNA led to the suppression of 3MC-induced FAT expression. In addition, the mRNA level of peroxisome proliferator-activated receptor (PPAR) α, an upstream factor of FAT, was increased in the livers of 3MC-treated mice. Taking together, AHR activation induces hepatic microvesicular steatosis by increasing the expression level of FAT.

  9. Modulation of human GABArho1 receptors by taurine.

    PubMed

    Ochoa-de la Paz, L D; Martínez-Dávila, I A; Miledi, R; Martínez-Torres, A

    2008-07-01

    A study was made of the effects of taurine on GABArho1 receptors expressed in Xenopus oocytes. The EC(50) and reversal potentials for GABA, taurine and glycine currents were 2.3+/-0.4 microM (-25+/-0.9 mV), 5+/-0.8mM (-27+/-0.4 mV) and 7+/-0.5mM (-22+/-0.6 mV), respectively. Co-application of GABA and taurine, revealed a taurine concentration-dependent biphasic-modulation of the receptor: at 0.3-30 microM taurine potentiated the GABA-currents, whereas at 0.3-30 mM the GABA-currents were reduced. In contrast glycine potentiated the GABA-currents at all concentrations tested. TPMPA, a GABA(C) specific receptor antagonist, also blocked effectively and reversibly the taurine and glycine currents. Finally, lanthanum and zinc modulated the currents generated by the three amino acids. Taurine is abundant in the retina and our observations suggest that taurine may play an important role modulating the retinal GABAergic transmission.

  10. TAURINE REGULATION OF VOLTAGE-GATED CHANNELS IN RETINAL NEURONS

    PubMed Central

    Rowan, Matthew JM; Bulley, Simon; Purpura, Lauren; Ripps, Harris; Shen, Wen

    2017-01-01

    Taurine activates not only Cl−-permeable ionotropic receptors, but also receptors that mediate metabotropic responses. The metabotropic property of taurine was revealed in electrophysiological recordings obtained after fully blocking Cl−-permeable receptors with an inhibitory “cocktail” consisting of picrotoxin, SR95531, and strychnine. We found that taurine’s metabotropic effects regulate voltage-gated channels in retinal neurons. After applying the inhibitory cocktail, taurine enhanced delayed outward rectifier K+ channels preferentially in Off-bipolar cells, and the effect was completely blocked by the specific PKC inhibitor, GF109203X. Additionally, taurine also acted through a metabotropic pathway to suppress both L- and N-type Ca2+ channels in retinal neurons, which were insensitive to the potent GABAB receptor inhibitor, CGP55845. This study reinforces our previous finding that taurine in physiological concentrations produces a multiplicity of metabotropic effects that precisely govern the integration of signals being transmitted from the retina to the brain. PMID:23392926

  11. Taurine in the osmoregulation of the Brattleboro rat

    SciTech Connect

    Nieminen, M.J.; Tuomisto, L.; Solatunturi, E.; Eriksson, L.; Paasonen, M.K.

    1988-01-01

    The function of taurine in mammalian osmoregulation was studied in the Brattleboro rat with hereditary hypothalamic diabetes insipidus (DI). DI rats are chronically dehydrated because of their inability to synthesize vasopressin. One day of water deprivation did not affect the water balance in rats with normal vasopressin synthesis, whereas DI rats were markedly dehydrated and lost considerably body weight. Taurine content and /sup 3/H-taurine accumulation by platelets were significantly higher in DI rats, with a further increase after one day of water deprivation. In DI rats, water deprivation also evoked a clear taurine increase in skeletal muscle and in the brain. These findings indicate that taurine has an osmoregulatory function in mammals.

  12. Lentiviral hepatitis B pseudotype entry requires sodium taurocholate co-transporting polypeptide and additional hepatocyte-specific factors.

    PubMed

    Meredith, L W; Hu, K; Cheng, X; Howard, C R; Baumert, T F; Balfe, P; van de Graaf, K F; Protzer, U; McKeating, J A

    2016-01-01

    Hepatitis B virus (HBV) is one of the world's major unconquered infections, resulting in progressive liver disease, and current treatments rarely cure infection. A limitation to discovering new therapies is our limited knowledge of HBV entry and dissemination pathways that hinders the development of in vitro culture systems. To address this gap in our understanding we optimized the genesis of infectious lentiviral pseudoparticles (HBVpps). The recent discovery that the bile salt transporter sodium taurocholate co-transporting polypeptide (NTCP) acts as a receptor for HBV enabled us to assess the receptor dependency of HBVpp infection. HBVpps preferentially infect hepatoma cells expressing NTCP, whereas other non-liver cells engineered to express NTCP do not support infection, suggesting that additional hepatocyte-specific factors are required for HBVpp internalization. These results highlight the value of the HBVpp system to dissect the pathways of HBV entry and dissemination.

  13. Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects.

    PubMed

    Kim, Chaekyun; Cha, Young-Nam

    2014-01-01

    Taurine is one of the most abundant non-essential amino acid in mammals and has many physiological functions in the nervous, cardiovascular, renal, endocrine, and immune systems. Upon inflammation, taurine undergoes halogenation in phagocytes and is converted to taurine chloramine (TauCl) and taurine bromamine. In the activated neutrophils, TauCl is produced by reaction with hypochlorite (HOCl) generated by the halide-dependent myeloperoxidase system. TauCl is released from activated neutrophils following their apoptosis and inhibits the production of inflammatory mediators such as, superoxide anion, nitric oxide, tumor necrosis factor-α, interleukins, and prostaglandins in inflammatory cells at inflammatory tissues. Furthermore, TauCl increases the expressions of antioxidant proteins, such as heme oxygenase 1, peroxiredoxin, thioredoxin, glutathione peroxidase, and catalase in macrophages. Thus, a central role of TauCl produced by activated neutrophils is to trigger the resolution of inflammation and protect macrophages and surrounding tissues from being damaged by cytotoxic reactive oxygen metabolites overproduced during inflammation. This is achieved by attenuating further production of proinflammatory cytokines and reactive oxygen metabolites and also by increasing the levels of antioxidant proteins that are able to scavenge and diminish the production of cytotoxic oxygen metabolites. These findings suggest that TauCl released from activated neutrophils may be involved in the recovery processes of cells affected by inflammatory oxidative stresses and thus TauCl could be used as a potential physiological agent to control pathogenic symptoms of chronic inflammatory diseases.

  14. Effect of fishmeal replacement by soy protein concentrate with taurine supplementation on growth performance, hematological and biochemical status, and liver histology of totoaba juveniles (Totoaba macdonaldi).

    PubMed

    López, Lus M; Flores-Ibarra, Maricela; Bañuelos-Vargas, Isaura; Galaviz, Mario A; True, Conal D

    2015-08-01

    The effect of dietary inclusion of soy protein concentrate (SPC) and simultaneous supplementation with taurine on the growth, hematology, blood biochemistry, and liver histology of totoaba (Totoaba macdonaldi) juveniles was assessed. Four isoproteic and isolipidic diets were formulated containing either 30 or 60% of SPC (diets S30 and S60), supplemented or not with 1% of taurine (diets S30T and S60T). A fishmeal-based diet formulated for totoaba nutritional requirements, without SPC and taurine supplementation, was used as a reference diet. Triplicate groups of 32 totoaba juveniles (average body weight 7.5 ± 0.6 g) were fed these diets for 45 days. Results showed that growth performance in fish fed S30, S30T, and S60T was similar to fish fed the reference diet. Red blood cells and hematocrit in fish fed with supplemented taurine in both levels of SPC (S30T and S60T) were similar to the fish fed the RD; the addition of taurine improved the state of hydration of totoaba. Plasmatic hemoglobin in fish fed the lower SPC level was similar to fish fed the RD. The mean corpuscular hemoglobin concentration in fish fed S30T was similar to fish fed the RD, taurine supplementation prevented the development of hypochromic anemia in this group of fish. Plasmatic albumin in fish fed S30 was similar to fish fed the RD. Plasmatic total protein and globulin concentration increased and AL:GLB (albumin:globulin ratio) decreased in fish fed the SPC-based diets despite taurine supplementation. The protein profile showed that taurine supplementation did not prevent a possible inflammatory process (increased globulins, decreased AL:GLB) in juvenile totoaba fed both levels of SPC. Glucose concentration was similar in fish fed S30, S30T, and S60T. The histological hepatic index was highest in fish fed S60. These results suggest that with an appropriate nutritional level, taurine may play an important modulatory role in the hematology and blood biochemistry status in totoaba fed SPC

  15. Taurine activates GABAergic networks in the neocortex of immature mice

    PubMed Central

    Sava, Bogdan A.; Chen, Rongqing; Sun, Haiyan; Luhmann, Heiko J.; Kilb, Werner

    2014-01-01

    Although it has been suggested that taurine is the main endogenous neurotransmitter acting on glycine receptors, the implications of glycine receptor-mediated taurine actions on immature neocortical networks have not been addressed yet. To investigate the influence of taurine on the excitability of neuronal networks in the immature neocortex, we performed whole-cell patch-clamp recordings from visually identified pyramidal neurons and interneurons in coronal slices from C57Bl/6 and GAD67-green fluorescent protein (GFP) transgenic mice (postnatal days 2–4). In 46% of the pyramidal neurons bath-application of taurine at concentrations ≥ 300 μM significantly enhanced the frequency of postsynaptic currents (PSCs) by 744.3 ± 93.8% (n = 120 cells). This taurine-induced increase of PSC frequency was abolished by 0.2 μM tetrodotoxin (TTX), 1 μM strychnine or 3 μM gabazine, but was unaffected by the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (±) R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), suggesting that taurine specifically activates GABAergic network activity projecting to pyramidal neurons. Cell-attached recordings revealed that taurine enhanced the frequency of action potentials (APs) in pyramidal neurons, indicating an excitatory action of the GABAergic PSCs. In order to identify the presynaptic targets of taurine we demonstrate that bath application of taurine induced in GAD67-GFP labeled interneurons an inward current that is mainly mediated by glycine receptors and can generate APs in these cells. We conclude from these results that taurine can enhance network excitability in the immature neocortex by selectively activating GABAergic interneurons via interactions with glycine receptors. PMID:24550782

  16. Exogenous folate ameliorates ethanol-induced brain hyperhomocysteinemia and exogenous ethanol reduces taurine levels in chick embryos.

    PubMed

    Barnett, Robert K; Booms, Stephanie L; Gura, Tracy; Gushrowski, Mara; Miller, Robert R

    2009-07-01

    The effects of exogenous ethanol and/or folic acid on endogenous homocysteine (HoCys) and SAM (S-adenosylmethionine)/SAH (S-adenosylhomocysteine) levels in chick brains were studied at 11 days of development. Embryonic EtOH (3.0 mmol/kg egg) exposure caused a 1.6-fold increase in brain HoCys levels and a 9-fold decrease in brain SAM/SAH levels as compared to controls (ptaurine levels, were studied at 18 days of development. A single dosage of EtOH (3.0 mmol/kg egg; E(0)) and two daily dosages of EtOH (E(0-1)) failed to influence brain and hepatic 10-FTHF DH activities when compared to controls. However, three daily dosages of EtOH (E(0-2)) caused approximately a two-fold increase in brain 10-FTHF DH activities and a three-fold increase in hepatic 10-FTHF DH activities as compared to controls (ptaurine levels in both brain and hepatic tissues (phepatic taurine levels as compared to controls (p

  17. Predicting carrier-mediated hepatic disposition of rosuvastatin in man by scaling from individual transfected cell-lines in vitro using absolute transporter protein quantification and PBPK modeling.

    PubMed

    Bosgra, Sieto; van de Steeg, Evita; Vlaming, Maria L; Verhoeckx, Kitty C; Huisman, Maarten T; Verwei, Miriam; Wortelboer, Heleen M

    2014-12-18

    In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter abundance between cell-lines and tissue is by using absolute protein quantification. In the present study, the performance of this strategy to predict human hepatic uptake transport was investigated and compared with traditional scaling from primary human hepatocytes. Rosuvastatin was used as a model compound. The uptake activity was measured in HEK293 cell-lines stably overexpressing OATP1B1(∗)1a, OATP1B3 or OATP2B1, the major transporters involved in human hepatic uptake of rosuvastatin, or expressing OATP1B1(∗)15, associated with reduced hepatic uptake of rosuvastatin. The abundance of these transporter proteins in the outer membranes of HEK293-cells, in human primary hepatocytes and in human liver tissue was determined by LC-MS/MS. The measured activity, corrected for protein abundance and scaled to the whole liver, gave a very accurate prediction of the hepatic intrinsic clearance observed in vivo. Embedded in a PBPK model describing the hepatic disposition and enterohepatic circulation, the collective in vitro data resulted in a good explanation of the observed oral and intravenous pharmacokinetic profiles of rosuvastatin. The model allowed simulation of the effect of polymorphic variants of OATP1B1 on rosuvastatin pharmacokinetics. These results encourage a larger scale validation. This approach may facilitate prediction of drug-drug interactions, scaling of transporter processes across subpopulations (children, diseased patients), and may be extended to tissues for which primary cells may be more difficult to obtain. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Triclosan Disrupts Thyroxine: Contribution of Hepatic Transport to the Mode of Action

    EPA Science Inventory

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) (TCS) decreases serum thyroxine (T4) in rats. In previous work, TCS upregulated Phase I and II hepatic metabolism after 4-day exposures in rats. A major data gap in our characterization of the mode of action (MOA) of TCS-induced ...

  19. Triclosan Disrupts Thyroxine: Contribution of Hepatic Transport to the Mode of Action

    EPA Science Inventory

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) (TCS) decreases serum thyroxine (T4) in rats. In previous work, TCS upregulated Phase I and II hepatic metabolism after 4-day exposures in rats. A major data gap in our characterization of the mode of action (MOA) of TCS-induced ...

  20. Inhibition of cholinergic response by taurine in frog isolated skeletal muscle.

    PubMed

    Lehmann, A; Hamberger, A

    1984-01-01

    Carbamylcholine-stimulated contractions of isolated frog gastrocnemius muscle were inhibited in a non-competitive fashion by 5-25 mM taurine. Taurine had no effect on the resting length of the muscle. Caffeine-induced contractures were unaffected by taurine which indicates that the sarcoplasmic reticulum is not an important site of action for taurine. A possible functional role for taurine in skeletal muscle is discussed.

  1. Effects of osmotic and light stimulation on 3H-taurine efflux from isolated rod outer segments and synthesis of tauret in the frog retina.

    PubMed

    Petrosian, A M; Haroutounian, J E; Fugelli, K; Kanli, H

    2000-01-01

    After injection of 3H-taurine into eyeballs of frogs and maintenance for 3 h in darkness by a gentle shaking, an almost homogenous fraction of rod outer segments (ROS) was prepared. About a 22% decrease in tonicity caused by reducing NaCl in isotonic 225 mOsm normal solution caused a rapid increase in the rate coefficient of efflux of 3H-taurine from the ROS fraction. The peak level of increased efflux rate coefficient was 7-times higher than the basal isotonic level. This indicates that taurine could contribute essentially to the volume regulation, either via selective channels or a carrier transporter-mediated pathways. For further clarifying if taurine fluxes in the ROS are sensitive to the light, other experiments were performed. Neither light stimulation of dark-adapted ROSs fractions or dark stimulation of weakly illuminated ROSs revealed any detectable changes in the efflux rate coefficient of 3H-taurine. These results indicate that light-induced taurine efflux, if present in the ROS, must be small, compared with hypoosmotic induced efflux. Thus the question of light-induced release of taurine from ROS still remains to be clarified. In the second part of this study, using TLC (thin layer chromatography) in combination with 3H-taurine measurements we have tried to clarify whether frogs (Rana ridibunda) eye structures can synthesize tauret (retinylidenetaurine). In isolated retinal preparations almost no any noticeable radioactivity was detected compared with background level. The capability of the eye structures to synthesize tauret from 3H-taurine was revealed in the second whole eye injection experiment. About 0.3% of the total 3H-taurine pool taken up was converted into 3H-tauret in the dark-adapted frog retina. In the retina of frogs adapted to light compared with those which were dark adapted tauret quantities were remarkable lower--on average about half. These results are in agreement with our recent data obtained by HPLC, which indicate tauret levels

  2. Hepatic excretory function in sepsis: implications from biophotonic analysis of transcellular xenobiotic transport in a rodent model

    PubMed Central

    2013-01-01

    Introduction Hepatobiliary elimination of endo- and xenobiotics is affected by different variables including hepatic perfusion, hepatocellular energy state and functional integrity of transporter proteins, all of which are altered during sepsis. A particular impairment of hepatocellular transport at the canalicular pole resulting in an accumulation of potentially hepatotoxic compounds would have major implications for critical care pharmacology and diagnostics. Methods Hepatic transcellular transport, that is, uptake and hepatobiliary excretion, was studied in a rodent model of severe polymicrobial sepsis by two different biophotonic techniques to obtain insights into the handling of potentially toxic endo- and xenobiotics in sepsis. Direct and indirect in vivo imaging of the liver was performed by intravital multifluorescence microscopy and non-invasive whole-body near-infrared (NIRF) imaging after administration of two different, primarily hepatobiliary excreted xenobiotics, the organic anionic dyes indocyanine green (ICG) and DY635. Subsequent quantitative data analysis enabled assessment of hepatic uptake and fate of these model substrates under conditions of sepsis. Results Fifteen hours after sepsis induction, animals displayed clinical and laboratory signs of multiple organ dysfunction, including moderate liver injury, cholestasis and an impairment of sinusoidal perfusion. With respect to hepatocellular transport of both dyes, excretion into bile was significantly delayed for both dyes and resulted in net accumulation of potentially cytotoxic xenobiotics in the liver parenchyma (for example, specific dye fluorescence in liver at 30 minutes in sham versus sepsis: ICG: 75% versus 89%; DY635 20% versus 40% of maximum fluorescence; P < 0.05). Transcutaneous assessment of ICG fluorescence by whole body NIRF imaging revealed a significant increase of ICG fluorescence from the 30th minute on in the bowel region of the abdomen in sham but not in septic animals

  3. Anti-inflammatory effects of taurine derivatives (taurine chloramine, taurine bromamine, and taurolidine) are mediated by different mechanisms.

    PubMed

    Marcinkiewicz, Janusz; Kurnyta, Maria; Biedroń, Rafał; Bobek, Małgorzata; Kontny, Ewa; Maśliński, Włodzimierz

    2006-01-01

    In this study, in an animal model of zymosan-induced peritonitis we have tested anti-inflammatory properties of Taurolidine (TRD), a synthetic derivative of taurine. In vitro, the effect of TRD and HOCl treated TRD on peritoneal macrophages was compared with that of TauCl. We report that locally administered TRD (Taurolin) shows strong anti-inflammatory properties. TRD inhibits vascular permeability increased by inflammatory stimuli; it also significantly attenuates the influx of neutrophils into the peritoneal cavity, as well as the production of pro-inflammatory cytokines (TNF-alpha, IL-6) by peritoneal exudate cells. Chlorination of TRD resulted in the formation of chloramine (TRD-Cl), as confirmed by characteristic UV spectra. Both TRD and TRD-Cl, more effectively than TauCl, inhibited the production of IL-6 by stimulated macrophages. The effect was not dependent on its well-known anti-endotoxin activity since TRD inhibited cytokine production by macrophages stimulated with either LPS or IFN-gamma. Finally, we report that anti-inflammatory activities of TRD and taurine haloamines are mediated by different mechanisms. TRD, in contrast to TauCl and TauBr, does not induce expression of HO-1, a stress inducible enzyme with strong anti-inflammatory properties.

  4. THE MODULATORY ROLE OF TAURINE IN RETINAL GANGLION CELLS

    PubMed Central

    Jiang, Zheng; Bulley, Simon; Guzzone, Joseph; Ripps, Harris; Shen, Wen

    2017-01-01

    Taurine (2-aminoethylsuphonic acid) is present in nearly all animal tissues, and is the most abundant free amino acid in muscle, heart, CNS and retina. Although it is known to be a major cytoprotectant and essential for normal retinal development, its role in retinal neurotransmission and modulation is not well understood. We investigated the response of taurine in retinal ganglion cells, and its effect on synaptic transmission between ganglion cells and their pre-synaptic neurons. We find that taurine-elicited currents in ganglion cells could be fully blocked by both strychnine and SR95531, glycine and GABAA receptor antagonists, respectively. This suggests that taurine-activated receptors might share the antagonists with GABA and glycine receptors. The effect of taurine at micromolar concentrations can effectively suppress spontaneous vesicle release from the pre-synaptic neurons, but had limited effects on light-evoked synaptic signals in ganglion cells. We also describe a metabotropic effect of taurine in the suppression of light-evoked response in ganglion cells. Clearly, taurine acts in multiple ways to modulate synaptic signals in retinal output neurons, ganglion cells. PMID:23392924

  5. Biophysical insight into the anti-amyloidogenic behavior of taurine.

    PubMed

    Chaturvedi, Sumit Kumar; Alam, Parvez; Khan, Javed Masood; Siddiqui, Mohd Khursheed; Kalaiarasan, Ponnusamy; Subbarao, Naidu; Ahmad, Zeeshan; Khan, Rizwan Hasan

    2015-09-01

    In this work, we investigated the inhibitory ability of taurine on the aggregation of Human serum albumin (HSA) and also examined how it controls the kinetic parameters of the aggregation process. We demonstrated the structural alterations in the HSA after binding to the taurine at 65 °C by exploiting various biophysical techniques. UV-vis spectroscopy was used to check the turbidometric changes in the protein. Thioflavin T fluorescence kinetics was subjected to explore kinetic parameters comparing the amyloid formation in the presence of varying concentration of taurine. Further, Congo red binding and ANS binding assays were performed to determine the inhibitory effect of taurine on HSA fibrillation process and surface hydrophobicity modifications occurring before and after the addition of taurine with protein, respectively. Far UV CD and Dynamic Light Scattering (DLS) confirmed that taurine stabilized the protein α-helical structure and formed complex with HSA which is further supported by differential scanning calorimetry (DSC). Moreover, microscopic imaging techniques were also done to analyze the morphology of aggregation formed. Taurine is also capable of altering the cytotoxicity of the proteinaceous aggregates. Molecular docking study also deciphered the possible residues involved in protein and drug interaction. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Interactions between taurine and ethanol in the central nervous system.

    PubMed

    Olive, M F

    2002-01-01

    This purpose of this review will be to summarize the interactions between the endogenous amino acid taurine and ethyl alcohol (ethanol) in the central nervous system (CNS). Taurine is one of the most abundant amino acids in the CNS and plays an integral role in physiological processes such as osmoregulation, neuroprotection and neuromodulation. Both taurine and ethanol exert positive allosteric modulatory effects on neuronal ligand-gated chloride channels (i.e., GABA(A) and glycine receptors) as well as inhibitory effects on other ligand- and voltage-gated cation channels (i.e., NMDA and Ca(2+) channels). Behavioral evidence suggests that taurine can alter the locomotor stimulatory, sedating, and motivational effects of ethanol in a strongly dose-dependent manner. Microdialysis studies have revealed that ethanol elevates extracellular levels of taurine in numerous brain regions, although the functional consequences of this phenomenon are currently unknown. Finally, taurine and several related molecules including the homotaurine derivative acamprosate (calcium acetylhomotaurinate) can reduce ethanol self-administration and relapse to drinking in both animals and humans. Taken together, these data suggest that the endogenous taurine system may be an important modulator of effects of ethanol on the nervous system, and may represent a novel therapeutic avenue for the development of medications to treat alcohol abuse and alcoholism.

  7. Taurine prevents collagen abnormalities in high fructose-fed rats.

    PubMed

    Nandhini, A T Anitha; Thirunavukkarasu, V; Anuradha, C V

    2005-08-01

    Accumulation of collagen and changes in its physiochemical properties contribute to the development of secondary complications of diabetes. We undertook this study to see the effects of taurine on the content and characteristics of collagen from tail tendon of rats fed with high fructose diet. The rats were divided into four groups of six each: control group (CON), taurine-supplemented control group (CON+TAU), taurine supplemented (FRU+TAU) and not supplemented fructose-fed group (FRU). The physico-chemical properties of collagen isolated from the tail tendon were studied. Fructose administration caused accumulation of collagen in tail tendon. Enhanced glycation and advanced glycation end products (AGE)-linked fluorescence together with alterations in aldehyde content, solubility pattern, susceptibility to denaturing agents and shrinkage temperature were observed in fructose-fed rats. Elevated b component of type I collagen was evidenced from the SDS gel pattern of collagen from the fructose-fed rats. Simultaneous administration of taurine alleviated these changes. Taurine administration to fructose-rats had a positive influence on both quantitative and qualitative properties of collagen. The results of the present study suggested a role for the action of taurine in delaying diabetic complications and the possible use of taurine as an adjuvant therapeutic measure in the management of diabetes and its complications.

  8. Effects of periconceptional undernutrition on maternal taurine concentrations in sheep.

    PubMed

    Thorstensen, Eric B; Derraik, José G B; Oliver, Mark H; Jaquiery, Anne L; Bloomfield, Frank H; Harding, Jane E

    2012-02-01

    Taurine has an important role in numerous physiological processes, including many aspects of fetal development such as development of the pancreas and brain, and requirements increase during pregnancy. Periconceptional undernutrition has long-term effects on pancreas and brain function of the offspring, but the effects on maternal taurine economy are unknown. We, therefore, studied the effects of different periods of periconceptional undernutrition on maternal plasma and urine taurine concentrations before and during pregnancy. Four groups of singleton-bearing ewes were studied (n 10-11): controls fed ad libitum, and groups undernourished from 60 d before until mating (PreC), from 2 d before mating until 30 d after mating (PostC) or from 60 d before until 30 d after mating (Pre+PostC). In PreC ewes, plasma taurine concentrations remained at control levels for the first 30 d, and then decreased through the remainder of undernutrition, but recovered by 30 d after mating; urinary taurine excretion was low at mating, but recovered similarly. In PostC ewes, plasma taurine concentrations recovered after 2 weeks despite ongoing undernutrition; urinary taurine excretion had recovered by 30 d after mating. Pre+PostC ewes followed the same pattern as PreC for the first 60 d, but plasma taurine concentrations and urinary excretion recovered slowly, and did not reach the control levels until 97 d. These data suggest that different periods of mild periconceptional undernutrition in sheep have different but substantial effects on maternal taurine homoeostasis. These effects may be one mechanism by which maternal periconceptional undernutrition alters development of the offspring with implications for adult health.

  9. Effect of Taurine on the antimicrobial efficiency of Gentamicin

    PubMed Central

    Islambulchilar, Mina; Sattari, Mohammad Reza; Sardashti, Mohammad; Lotfipour, Farzaneh

    2011-01-01

    Context: Gentamicin is mainly used in severe infections caused by gram-negatives. However toxicity including nephrotoxicity and ototoxicity is one of the most important complications of its treatment. The production of free radicals seems to be involved in gentamicin toxicity mechanism. Taurine, a major intracellular free β-amino acid, is known to be an endogenous antioxidant. So potentially the co-therapy of taurine and gentamicin would reduce the adverse effects of the antibiotic. Objectives: In this study, we wished to know the effect of taurine on the antibiotic capacity of gentamicin. Methods: strainsof P. aeruginosa, E. coli, S. aureus and S. epidermidis were used as test organisms. Minimum inhibitory concentrations of gentamicin in the presence and absence of taurine at quantities from 40 to 2 mg/L were determined using macro-dilution method. Results: MICs were determined in the various concentrations of taurine for bacterial indicators. The MIC values of gentamicin for P. aeruginosa, S. aureus and E. coli remained unchanged in the values of 2.5, 5 and 20 μg/ml respectively in the absence and presences of different concentrations of taurine. The bactericidal activity of gentamicin against S. epidermidis was increased by addition of taurine in the concentrations higher than 6 mg/L. Conclusion: According to our study the antibacterial activity of gentamicin against the indicator microorganisms were not interfere with taurine at selected concentrations. Further in vivo studies are needed to establish if a combination of gentamicin and taurine would have the same effect. PMID:24312759

  10. Calcium carbonate crystallization in the presence of taurine.

    PubMed

    Malkaj, P; Pierri, E; Dalas, E

    2006-05-01

    The kinetics of calcite (CaCO(3)) crystallization on calcite seed crystals in the presence of taurine was investigated by the constant composition method. The presence of taurine (4 x 10(- 5)- 4 x 10(-4)M) in the supersaturated solutions lead to calcite crystals with a characteristic discontinuous planes of growth and poor habit, as compared to the hombohedral morphology of the seed crystals. The acceleration effect of taurine on the crystal growth rate was 17-96%. The apparent order of the crystal growth was found to be 2.0+/- 0.2 typical for a surface diffusion-controlled spiral growth processes.

  11. Taurine deficiency in Newfoundlands fed commercially available complete and balanced diets.

    PubMed

    Backus, Robert C; Cohen, Gabrielle; Pion, Paul D; Good, Kathryn L; Rogers, Quinton R; Fascetti, Andrea J

    2003-10-15

    To determine taurine status in a large group of Newfoundlands related by environment, diet, or breeding to a dog with dilated cardiomyopathy and taurine deficiency. Prospective study. 19 privately owned Newfoundlands between 5 months and 11.5 years old that had been fed commercial dry diets meeting established nutrient recommendations. Diet histories were obtained, and blood, plasma, and urine taurine concentrations and plasma methionine and cysteine concentrations were measured. In 8 dogs, taurine concentrations were measured before and after supplementation with methionine for 30 days. Ophthalmic examinations were performed in 16 dogs; echocardiography was performed in 6 dogs that were taurine deficient. Plasma taurine concentrations ranged from 3 to 228 nmol/mL. Twelve dogs had concentrations < 40 nmol/mL and were considered taurine deficient. For dogs with plasma concentrations < 40 nmol/mL, there was a significant linear correlation between plasma and blood taurine concentrations. For dogs with plasma concentrations > 40 nmol/mL, blood taurine concentrations did not vary substantially. Taurine-deficient dogs had been fed lamb meal and rice diets. Retinal degeneration, dilated cardiomyopathy, and cystinuria were not found in any dog examined for these conditions. The taurine deficiency was reversed by a change in diet or methionine supplementation. Results indicate a high prevalence of taurine deficiency among an environmentally and genetically related cohort of Newfoundlands fed apparently complete and balanced diets. Blood taurine concentrations indicative of taurine deficiency in Newfoundlands may be substantially less than concentrations indicative of a deficiency in cats.

  12. Effect of allyl alcohol on hepatic transporter expression: Zonal patterns of expression and role of Kupffer cell function

    SciTech Connect

    Campion, Sarah N.; Tatis-Rios, Cristina; Augustine, Lisa M.; Goedken, Michael J.; Rooijen, Nico van; Cherrington, Nathan J.; Manautou, Jose E.

    2009-04-01

    During APAP toxicity, activation of Kupffer cells is critical for protection from hepatotoxicity and up-regulation of multidrug resistance-associated protein 4 (Mrp4) in centrilobular hepatocytes. The present study was performed to determine the expression profile of uptake and efflux transporters in mouse liver following treatment with allyl alcohol (AlOH), a periportal hepatotoxicant. This study also investigated the role of Kupffer cells in AlOH hepatotoxicity, and whether changes in transport protein expression by AlOH are dependent on the presence of Kupffer cells. C57BL/6J mice received 0.1 ml clodronate liposomes to deplete Kupffer cells or empty liposomes 48 h prior to dosing with 60 mg/kg AlOH, i.p. Hepatotoxicity was assessed by plasma ALT and histopathology. Hepatic transporter mRNA and protein expression were determined by branched DNA signal amplification assay and Western blotting, respectively. Depletion of Kupffer cells by liposomal clodronate treatment resulted in heightened susceptibility to AlOH toxicity. Exposure to AlOH increased mRNA levels of several Mrp genes, while decreasing organic anion transporting polypeptides (Oatps) mRNA expression. Protein analysis mirrored many of these mRNA changes. The presence of Kupffer cells was not required for the observed changes in uptake and efflux transporters induced by AlOH. Immunofluorescent analysis revealed enhanced Mrp4 staining exclusively in centrilobular hepatocytes of AlOH treated mice. These findings demonstrate that Kupffer cells are protective from AlOH toxicity and that induction of Mrp4 occurs in liver regions away from areas of AlOH damage independent of Kupffer cell function. These results suggest that Kupffer cell mediators do not play a role in mediating centrilobular Mrp4 induction in response to periportal damage by AlOH.

  13. Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept.

    PubMed

    Zielińska, Magdalena; Popek, Mariusz; Albrecht, Jan

    2014-01-01

    Excessive glutamine (Gln) synthesis in ammonia-overloaded astrocytes contributes to astrocytic swelling and brain edema, the major complication of hepatic encephalopathy (HE). Much of the newly formed Gln is believed to enter mitochondria, where it is recycled to ammonia, which causes mitochondrial dysfunction (a "Trojan horse" mode of action). A portion of Gln may increase osmotic pressure in astrocytes and the interstitial space, directly and independently contributing to brain tissue swelling. Here we discuss the possibility that altered functioning of Gln transport proteins located in the cellular or mitochondrial membranes, modulates the effects of increased Gln synthesis. Accumulation of excess Gln in mitochondria involves a carrier-mediated transport which is activated by ammonia. Studies on the expression of the cell membrane N-system transporters SN1 (SNAT3) and SN2 (SNAT5), which mediate Gln efflux from astrocytes rendered HE model-dependent effects. HE lowered the expression of SN1 at the RNA and protein level in the cerebral cortex (cc) in the thioacetamide (TAA) model of HE and the effect paralleled induction of cerebral cortical edema. Neither SN1 nor SN2 expression was affected by simple hyperammonemia, which produces no cc edema. TAA-induced HE is also associated with decreased expression of mRNA coding for the system A carriers SAT1 and SAT2, which stimulate Gln influx to neurons. Taken together, changes in the expression of Gln transporters during HE appear to favor retention of Gln in astrocytes and/or the interstitial space of the brain. HE may also affect arginine (Arg)/Gln exchange across the astrocytic cell membrane due to changes in the expression of the hybrid Arg/Gln transporter y(+)LAT2. Gln export from brain across the blood-brain barrier may be stimulated by HE via its increased exchange with peripheral tryptophan.

  14. Effect of Traumatic Brain Injury, Erythropoietin, and Anakinra on Hepatic Metabolizing Enzymes and Transporters in an Experimental Rat Model.

    PubMed

    Anderson, Gail D; Peterson, Todd C; Vonder Haar, Cole; Farin, Fred M; Bammler, Theo K; MacDonald, James W; Kantor, Eric D; Hoane, Michael R

    2015-09-01

    In contrast to considerable data demonstrating a decrease in cytochrome P450 (CYP) activity in inflammation and infection, clinically, traumatic brain injury (TBI) results in an increase in CYP and UDP glucuronosyltransferase (UGT) activity. The objective of this study was to determine the effects of TBI alone and with treatment with erythropoietin (EPO) or anakinra on the gene expression of hepatic inflammatory proteins, drug-metabolizing enzymes, and transporters in a cortical contusion impact (CCI) injury model. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h, and 7 days post-CCI. Plasma cytokine and liver protein concentrations of CYP2D4, CYP3A1, EPHX1, and UGT2B7 were determined. There was no effect of TBI, TBI + EPO, or TBI + anakinra on gene expression of the inflammatory factors shown to be associated with decreased expression of hepatic metabolic enzymes in models of infection and inflammation. IL-6 plasma concentrations were increased in TBI animals and decreased with EPO and anakinra treatment. There was no significant effect of TBI and/or anakinra on gene expression of enzymes or transporters known to be involved in drug disposition. TBI + EPO treatment decreased the gene expression of Cyp2d4 at 72 h with a corresponding decrease in CYP2D4 protein at 72 h and 7 days. CYP3A1 protein was decreased at 24 h. In conclusion, EPO treatment may result in a significant decrease in the metabolism of Cyp-metabolized drugs. In contrast to clinical TBI, there was not a significant effect of experimental TBI on CYP or UGT metabolic enzymes.

  15. Effect of concentration on hepatic transport of exogenous epidermal growth factor

    SciTech Connect

    Burwen, S.J.; Barker, M.E.; Goldman, I.S.; Jones, A.L.

    1985-03-01

    Epidermal growth factor (EGF), taken up by rat hepatocytes, is primarily transported to the lysosomes and degraded. However, a small but significant percentage of endocytosed EGF is transported by a nonlysosomal pathway and is secreted intact into bile. There is no information as to the mechanisms that regulate the selection of transport pathway and thereby determine the different metabolic fates for EGF. The experiments reported here were undertaken to determine whether the amount of exogenous EGF administered to the liver (the transport load) might affect the selection of the transport pathway. If ''excess'' EGF, exceeding some as yet undetermined threshold, is preferentially transported by the lysosomal pathway, then the proportion of degraded EGF secreted into bile should increase as a function of the amount of EGF administered. /sup 125/I-EGF (3 to 175 ng) was injected into rat portal veins, and bile samples were collected via cannula. The radioactivity secreted into bile was measured, and the bile samples were immunoprecipitated with anti-EGF antiserum. The proportion of intact vs. degraded EGF in bile was determined by the percentage of immunoprecipitable radioactivity. Regardless of the amount of EGF injected, the pattern of its secretion was unaltered. The percentage of immunoprecipitable EGF in bile was the same for all doses. Therefore, the amount of EGF that was degraded did not change as a function of EGF concentration, implying that the lysosomal pathway was not preferentially utilized as the transport load increased.

  16. Separation methods for taurine analysis in biological samples.

    PubMed

    Mou, Shifen; Ding, Xiaojing; Liu, Yongjian

    2002-12-05

    Taurine plays an important role in a variety of physiological functions, pharmacological actions and pathological conditions. Many methods for taurine analysis, therefore, have been reported to monitor its levels in biological samples. This review discusses the following techniques: sample preparation; separation and determination methods including high-performance liquid chromatography, gas chromatography, ion chromatography, capillary electrophoresis and hyphenation procedures. It covers articles published between 1990 and 2001.

  17. Effect of taurine on rat Achilles tendon healing.

    PubMed

    Akdemir, Ovunc; Lineaweaver, William C; Cavusoglu, Turker; Binboga, Erdal; Uyanikgil, Yigit; Zhang, Feng; Pekedis, Mahmut; Yagci, Tugay

    2015-01-01

    Taurine has anti-inflammatory and antioxidant characteristics. We have introduced taurine into a tendon-healing model to evaluate its effects on tendon healing and adhesion formation. Two groups of 16 rats underwent diversion and repair of the Achilles tendon. One group received a taurine injection (200 mg/ml) at the repair site, while the other group received 1 ml of saline. Specimens were harvested at 6 weeks and underwent biomechanical and histological evaluation. No tendon ruptured. Average maximum load was significantly greater in the taurine-applied group compared with the control group (p < 0.05). Similarly, average energy uptake was significantly higher in the taurine-applied group compared with the control group (p < 0.05). We observed no significant differences in stiffness in both groups (p > 0.05). After histological assessment, we found that fibroblast proliferation, edema, and inflammation statistically decreased in the treatment group (p < 0.05). These findings could indicate greater tendon strength with less adhesion formation, and taurine may have an effect on adhesion formation.

  18. Improvement of Impaired Memory in Mice by Taurine

    PubMed Central

    Vohra, Bhupinder P. S.; Hui, Xiang

    2000-01-01

    Taurine was extracted from Pegasus later-narius Cuvier to study its effects on learning and memory in mice. Mice were treated with different doses of taurine (10 mg/kg, 20 mg/kg, 40 mg/kg). The mice were treated with various chemical agents (pentobarbital, cycloheximide, sodium nitrite, alcohol) to disrupt the normal memory process. We measured the effect of taurine on step-down latency (SDL) and escape latency (EL) in a passive avoidance task after 10 or 30 days. Treatment with taurine alone did not change either SDL or EL. Taurine protected mice .from the memory disruption induced by alcohol, pentobarbital, sodium nitrite, and cycloheximide but had no obvious effect on motor coordination, exploratory activity, or locomotor activity as measured using the rota-rod test and the hole board test. We conclude that taurine can be effective in attenuating the amnesia produced by alcohol, pentobarbital, cycloheximide, and sodium nitrite without compromising the behavioral aspects of the animals tested. PMID:11486485

  19. Protective effects of taurine against closed head injury in rats.

    PubMed

    Sun, Ming; Zhao, Yumei; Gu, Yi; Zhang, Yazhuo

    2015-01-01

    Taurine, an abundant amino acid in the nervous system, is reported to reduce ischemic brain injury in a dose-dependent manner. This study was designed to investigate whether taurine protected the brain against closed head injury (CHI) in rats. Taurine was administered intravenously 30 min after CHI. It was found that taurine lessened body-weight loss and improved neurological functions at 7 days after CHI. Moreover, it lowered brain edema and blood-brain barrier permeability, enhanced activity of superoxide dismutase and the level of glutathione, and reduced levels of malondialdehyde and lactic acid in traumatic tissue 24 h after CHI. In addition, it attenuated neuronal cell death in hippocampal CA1 and CA3 subfields 7 days after CHI. All of these effects were dose dependent. These data demonstrated the dose-dependent protection of taurine against experimental CHI and suggest that taurine treatment might be beneficial in reducing trauma-induced oxidative damage to the brain, thus showing the potential for clinical implications.

  20. Effects of taurine on gut microbiota and metabolism in mice.

    PubMed

    Yu, Haining; Guo, Zhengzhao; Shen, Shengrong; Shan, Weiguang

    2016-07-01

    As being a necessary amino acid, taurine plays an important role in the regulation of neuroendocrine functions and nutrition. In this study, effects of taurine on mice gut microbes and metabolism were investigated. BALB/C mice were randomly divided into three experimental groups: The first group was administered saline (CK), the second was administered 165 mg/kg natural taurine (NE) and the third one administered 165 mg/kg synthetic taurine (CS). Gut microbiota composition in mice feces was analyzed by metagenomics technology, and the content of short-chain fatty acids (SCFA) in mice feces was detected by gas chromatography (GC), while the concentrations of lipopolysaccharide (LPS) and superoxide dismutase (SOD) were detected by a LPS ELISA kit and a SOD assay kit, respectively. The results showed that the effect of taurine on gut microbiota could reduce the abundance of Proteobacteria, especially Helicobacter. Moreover, we found that the SCFA content was increased in feces of the NE group while LPS content was decreased in serum of the NE group; the SOD activity in serum and livers of the NE and CS groups were not changed significantly compare to that of the CK group. In conclusion, taurine could regulate the gut micro-ecology, which might be of benefit to health by inhibiting the growth of harmful bacteria, accelerating the production of SCFA and reducing LPS concentration.

  1. Taurine in milk and yoghurt marketed in Italy.

    PubMed

    Manzi, Pamela; Pizzoferrato, Laura

    2013-02-01

    Taurine, a free amino acid, was studied as natural compound of different typologies of milk: pasteurized, ultra-high temperature (UHT), microfiltered whole and semi-skimmed cow's milk; pasteurized and UHT goat's whole milk and raw buffalo's whole milk. Moreover, taurine contents in yoghurt from cow and goat's milk were evaluated. The data obtained in this research showed that no significant variations of taurine occurred in cow's milk subjected to different technological processes and between whole and semi-skimmed milk. The amount of taurine was less (p < 0.05) in cow's milk (0.60 mg/100 g) than in goat and buffalo's milk (6.55 and 7.32 mg/100 g, respectively). No significant differences in taurine occurred between goat and buffalo's samples. The amounts of taurine in yoghurt reflected, substantially, the content of this molecule in the milk of the relevant animal species. These results are noteworthy because data available in the literature on this molecule in commercial dairy products are old or few.

  2. Relative contribution of diet and biosynthesis to the taurine content of the adult rat.

    PubMed

    Huxtable, R J; Lippincott, S E

    1982-01-01

    The relative contribution of diet and biosynthesis to the taurine content of the rat has been determined quantitatively under various dietary conditions. Rats were maintained on diets containing [3H]taurine and/or [35S]methionine of known amounts and specific activities, and subsequently the specific activity of taurine in various tissues was determined. This approach gives a quantitative measure of how much taurine is biosynthesized versus how much is derived from the diet regardless of the biosynthetic route or site of biosynthesis in the animal. With no taurine in the diet, over an 87-day period, 54% of the taurine in the animal had been biosynthesized. This fell to 29% if taurine was present in the diet, and the contribution of dietary taurine to body pools rose to 58%. These changes in biosynthetic contributions were not accompanied by an alteration in the rate of biosynthesis but by an alteration in rate of excretion. When the amounts of biosynthesized taurine appearing in the urine over 63 days was added to the amounts found in the carcass, 3.1 mmol were found to be biosynthesized by animals receiving taurine in the diet as compared to 2.9 mmol in animals on a taurine-deficient diet. In any one experiment, the contribution of diet or biosynthesis is invariant from tissue to tissue indicating that the rate of exchange of taurine between tissues is faster than the rate of elimination of taurine from the body.

  3. Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.

    PubMed Central

    Ganguly, T C; Liu, Y; Hyde, J F; Hagenbuch, B; Meier, P J; Vore, M

    1994-01-01

    We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity. Images Figure 2 PMID:7945260

  4. Minimal role of hepatic transporters in the hepatoprotection against LCA-induced intrahepatic cholestasis.

    PubMed

    Beilke, Lisa D; Besselsen, David G; Cheng, Quiqiong; Kulkarni, Supriya; Slitt, Angela L; Cherrington, Nathan J

    2008-03-01

    The multidrug resistance-associated proteins (Mrps) are a family of adenosine triphosphate-dependent transporters that facilitate the movement of various compounds, including bile acids, out of hepatocytes. The current study was conducted to determine whether induction of these transporters alters bile acid disposition as a means of hepatoprotection during bile acid-induced cholestasis. Lithocholic acid (LCA) was used to induce intrahepatic cholestasis. C57BL/6 mice were pretreated with corn oil (CO) or known transporter inducers, phenobarbital (PB), oltipraz (OPZ), or TCPOBOP (TC) for 3 days prior to cotreatment with LCA and inducer for 4 days. Histopathology revealed that PB and TC pretreatments provide a protective effect from LCA-induced toxicity, whereas OPZ pretreatment did not. Both PB/LCA and TC/LCA cotreatment groups also had significantly lower alanine aminotransferase values than the LCA-only group. In TC/LCA cotreated mice compared with LCA only, messenger RNA (mRNA) expression of uptake transporters Ntcp and Oatp4 was significantly increased, as were sinusoidal efflux transporters Mrp3 and Mrp4. Although in PB/LCA cotreated mice, the only significant change compared with LCA-only treatment was an increase in uptake transporter Oatp4. Oatp1 was reduced in all groups compared with CO controls. No significant changes in mRNA expression were observed in Oatp2, Bsep, Mrp2, Bcrp, Mrp1, Mrp5, or Mrp6. Mrp4 protein expression was induced in the OPZ/LCA and TC/LCA cotreated groups, whereas Mrp3 protein levels remained unchanged between groups. Protein expression of Mrp1 and Mrp5 was increased in the unprotected LCA-only and OPZ/LCA mice. Thus, transporter expression did not correlate with histologic hepatoprotection, however, there was a correlation between hepatoprotection and significantly reduced total liver bile acids in the PB/LCA and TC/LCA cotreated mice compared with LCA only. In conclusion, changes in transporter expression did not correlate with

  5. Regulation of hepatic EAAT-2 glutamate transporter expression in human liver cholestasis

    PubMed Central

    Najimi, Mustapha; Stéphenne, Xavier; Sempoux, Christine; Sokal, Etienne

    2014-01-01

    AIM: To investigate the activity and expression of EAAT2 glutamate transporter in both in vitro and in vivo models of cholestasis. METHODS: This study was conducted on human hepatoblastoma HepG2 cell cultures, the liver of bile duct ligated rats and human specimens from cholestatic patients. EAAT2 glutamate transporter activity and expression were analyzed using a substrate uptake assay, immunofluorescence, reverse transcription-polymerase chain reaction, and immunohistochemistry, respectively. RESULTS: In HepG2 cells, cholestasis was mimicked by treating cells with the protein kinase C activator, phorbol 12-myristate 13-acetate. Under such conditions, EAAT2 transporter activity was decreased both at the level of substrate affinity and maximal transport velocity. The decreased uptake was correlated with intracellular translocation of EAAT2 molecules as demonstrated using immunofluorescence. In the liver of bile duct ligated rats, an increase in EAAT2 transporter protein expression in hepatocytes was demonstrated using immunohistochemistry. The same findings were observed in human liver specimens of cholestasis in which high levels of γ-glutamyl transpeptidase were documented in patients with biliary atresia and progressive familial intrahepatic cholestasis type 3. CONCLUSION: This study demonstrates the alteration in glutamate handling by hepatocytes in liver cholestasis and suggests a potential cross-talk between glutamatergic and bile systems. PMID:24587631

  6. /sup 13/C nuclear magnetic resonance study of the complexation of calcium by taurine

    SciTech Connect

    Irving, C.S.; Hammer, B.E.; Danyluk, S.S.; Klein, P.D.

    1980-01-01

    /sup 13/C Nuclear magnetic resonance chemical shifts, /sup 1/J/sub c-c/ scalar coupling constants, spin-lattice relaxation times, and nuclear Overhauser effects were determined for taurine-(1, 2 /sup 13/C) and a taurine-(1 /sup 13/C) and taurine-(2 /sup 13/C) mixture in the presence and absence of calcium. Comparison of taurine titration shifts to values for related compounds reveals some unusual electronic properties of the taurine molecule. Stability constants of 1:1 calcium complexes with taurine zwitterions and anions, as well as their /sup 13/C chemical shifts, were obtained by least squares analysis of titration curves measured in the presence of calcium. The stability constants of calcium-taurine complexes were significantly lower than previous values and led to estimates that only approximately one percent of intracellular calcium of mammalian myocardial cells would exist in a taurine complex.

  7. Functions of Maternally-Derived Taurine in Fetal and Neonatal Brain Development.

    PubMed

    Tochitani, Shiro

    2017-01-01

    Taurine (2-aminoethanesulfonic acid) is a sulfur-containing organic acid, which has various physiological functions, including membrane stabilization, cell-volume regulation, mitochondrial protein translocation, anti-oxidative activity, neuroprotection against neurotoxicity and modulation of intracellular calcium levels. Taurine also activates GABAA receptors and glycine receptors. Mammalian fetuses and infants are dependent on taurine delivered from their mothers via either the placenta or their mother's milk. Taurine is a molecule that links mother-fetus or mother-infant bonding.This review describes the functions of taurine and the mechanisms of action of taurine in fetal and brain development. Taurine is involved in regulating the proliferation of neural progenitors, migration of newly-generated neurons, and the synapse formation of neurons after migration during fetal and neonatal development. In this review, we also discuss the environmental factors that might influence the functional roles of taurine in neural development.

  8. Activation of synaptic and extrasynaptic glycine receptors by taurine in preoptic hypothalamic neurons.

    PubMed

    Bhattarai, Janardhan Prasad; Park, Soo Joung; Chun, Sang Woo; Cho, Dong Hyu; Han, Seong Kyu

    2015-11-03

    Taurine is an essential amino-sulfonic acid having a fundamental function in the brain, participating in both cell volume regulation and neurotransmission. Using a whole cell voltage patch clamp technique, the taurine-activated neurotransmitter receptors in the preoptic hypothalamic area (PHA) neurons were investigated. In the first set of experiments, different concentrations of taurine were applied on PHA neurons. Taurine-induced responses were concentration-dependent. Taurine-induced currents were action potential-independent and sensitive to strychnine, suggesting the involvement of glycine receptors. In addition, taurine activated not only α-homomeric, but also αβ-heteromeric glycine receptors in PHA neurons. Interestingly, a low concentration of taurine (0.5mM) activated glycine receptors, whereas a higher concentration (3mM) activated both glycine and gamma-aminobutyric acid A (GABAA) receptors in PHA neurons. These results suggest that PHA neurons are influenced by taurine and respond via glycine and GABAA receptors.

  9. Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth

    USDA-ARS?s Scientific Manuscript database

    Taurine is a beta-amino sulfur amino acid found in most animal tissues. It has many important biological functions in mammals including membrane stabilization, antioxidation, cellular osmoregulation, detoxification, neuromodulation, and brain and eye development. Taurine supplementation in juvenil...

  10. Two different conformations in hepatitis C virus p7 protein account for proton transport and dye release.

    PubMed

    Gan, Siok Wan; Surya, Wahyu; Vararattanavech, Ardcharaporn; Torres, Jaume

    2014-01-01

    The p7 protein from the hepatitis C virus (HCV) is a 63 amino acid long polypeptide that is essential for replication, and is involved in protein trafficking and proton transport. Therefore, p7 is a possible target for antivirals. The consensus model for the channel formed by p7 protein is a hexameric or heptameric oligomer of α-helical hairpin monomers, each having two transmembrane domains, TM1 and TM2, where the N-terminal TM1 would face the lumen of this channel. A reported high-throughput functional assay to search for p7 channel inhibitors is based on carboxyfluorescein (CF) release from liposomes after p7 addition. However, the rationale for the dual ability of p7 to serve as an ion or proton channel in the infected cell, and to permeabilize membranes to large molecules like CF is not clear. We have recreated both activities in vitro, examining the conformation present in these assays using infrared spectroscopy. Our results indicate that an α-helical form of p7, which can transport protons, is not able to elicit CF release. In contrast, membrane permeabilization to CF is observed when p7 contains a high percentage of β-structure, or when using a C-terminal fragment of p7, encompassing TM2. We propose that the reported inhibitory effect of some small compounds, e.g., rimantadine, on both CF release and proton transport can be explained via binding to the membrane-inserted C-terminal half of p7, increasing its rigidity, in a similar way to the influenza A M2-rimantadine interaction.

  11. Taurine Regulates Mitochondrial Function During 7,12-Dimethyl Benz[a]anthracene Induced Experimental Mammary Carcinogenesis

    PubMed Central

    Vanitha, Manickam Kalappan; Priya, Kalpana Deepa; Baskaran, Kuppusamy; Periyasamy, Kuppusamy; Saravanan, Dhravidamani; Venkateswari, Ramachandran; Mani, Balasundaram Revathi; Ilakkia, Aruldass; Selvaraj, Sundaramoorthy; Menaka, Rajendran; Geetha, Mahendran; Rashanthy, Nadarajah; Anandakumar, Pandi; Sakthisekaran, Dhanapal

    2015-01-01

    Objectives: The present study was undertaken to determine the modulatory effect of taurine on the liver mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, major tricarboxylic acid cycle enzymes, and electron transport chain enzymes during 7,12-dimethyl benz[a]anthracene (DMBA) induced breast cancer in Sprague-Dawley rats. Methods: Animals in which breast cancer had been induced by using DMBA (25 mg/kg body weight) showed an increase in mitochondrial LPO together with decreases in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, and vitamin E), in citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha ketoglutarate dehydrogenase (alpha KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and in electron transport chain (ETC) complexes. Results: Taurine (100 mg/kg body weight) treatment decreased liver mitochondrial LPO and augmented the activities/levels of enzymic, and non-enzymic antioxidants, tricarboxylic acid cycle enzymes and ETC complexes. Conclusion: The results of our present study demonstrated the chemotherapeutic efficacy of taurine treatment for DMBA-induced breast carcinomas. PMID:26389003

  12. Anti-Inflammatory Effect of Taurine in Burned Patients

    PubMed Central

    Lak, Sima; Ostadrahimi, Alireza; Nagili, Behrooz; Asghari-Jafarabadi, Mohammad; Beigzali, Sanaz; Salehi, Feridoon; Djafarzadeh, Roxana

    2015-01-01

    Purpose: Burn induced inflammatory response can be mediated by reactive oxygen metabolites and accompanied by multiple organ dysfunction. Taurine has protective effects against various inflammatory conditions. The aim of this study was to determine the effect of Taurine supplement in thermal burn victims. Methods: Thirty patients with severe thermal burns were enrolled in this randomized double-blinded clinical trial. These patients were randomly divided into two equal groups (namely Control and Taurine groups), where both received isocaloric and isonitrogenous formula. One group was supplemented with 50 mg/kg of Taurine per day for a duration of 10 days. Blood samples were obtained to measure Interleukin-10 (IL-10), high-sensitivity C-reactive protein (hs-CRP), and Tumor Necrosis Factor alpha (TNF-α) levels at the beginning and the end of the study. Results: Change in serum level of IL-10 in Taurine group was more than Control group [-13.60(-31.40, -10.40) compared to -4.00(-20.00, -0.20) respectively; P = 0.030]. This change was significant in patients with more than 30% TBSA of burn [-14.20(-31.40, -10.40) compared to -2.40(-9.60, 0.40) respectively; P = 0.013]. As for the hs-CRP and TNF-α levels, the difference between the two groups were not significant. Conclusion: Based on the results obtained, Taurine supplement showed a positive outcome on anti-inflammatory cytokine IL-10 in all burn patients. This effect was even more significant in patients with higher percentage of burn area. Taurine had no significant effect on the inflammatory marker hs-CRP and the pro-inflammatory cytokine TNF-α level. For a more thorough verification, measurement of a wider range of inflammatory cytokines in more frequent time intervals are suggested. PMID:26819926

  13. [Plasma taurine levels in patients with esophagus cancer].

    PubMed

    Lamônica-Garcia, Vânia Cristina; Marin, Flávia Andréa; Lerco, Mauro Masson; Moreto, Fernando; Henry, Maria Aparecida Coelho Arruda; Burini, Roberto Carlos

    2008-01-01

    The esophagus cancer-host has a two way close relationship as seen in its sulphur-amino acid metabolism. Taurine one of these compounds has ubiquous role in host defense and other physiological mechanisms related to survival. To study the plasma levels of taurine and its precursors in patients with esophagus cancer. In a sectional design both groups, patients (n = 16, 43-73 yrs old) and healthy controls (n = 20, 27-65 yrs old) were assessed for anthropometry, body-weight lost, hematology (Hb, Ht, total leukocytes and lymphocyte counts), general biochemistry (albumin, glucose, lipids and aminotransferases) and chromatographic analysis for taurine, cysteine, and homocysteine. The survival time was registered there since from the clinical-histopathological diagnosis. All participants had a written ethical consent for the research. The cancer patients were predominantly, white males of low social economic class, with spinocellular carcinoma stage IV located at upper 3rd half of them presented hypoalbuminemia and 16% referred significant body-weight loss. The patients showed statistically lower values of Hb, Ht, total and HDL cholesterol and cysteine and significantly higher values of taurine, homocysteine and aminotransferases than healthy controls. A positive relationship was found between taurine and either TLC (r = 0.50) and survival (r = 0.81). Lower plasma cysteine along with higher levels of taurine and homocysteine and the positive direct association of taurine with indications of survival suggest an effective role of this compound and therefore a prospective special nutritional care in its precursors (cysteine, methionine and B vitamins) of these patients.

  14. Taurine supplementation modulates glucose homeostasis and islet function.

    PubMed

    Carneiro, Everardo M; Latorraca, Marcia Q; Araujo, Eliana; Beltrá, Marta; Oliveras, Maria J; Navarro, Mónica; Berná, Genoveva; Bedoya, Francisco J; Velloso, Licio A; Soria, Bernat; Martín, Franz

    2009-07-01

    Taurine is a conditionally essential amino acid for human that is involved in the control of glucose homeostasis; however, the mechanisms by which the amino acid affects blood glucose levels are unknown. Using an animal model, we have studied these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT). Islet cell function was determined by insulin secretion, cytosolic Ca2+ measurements and glucose metabolism from isolated islets. Islet cell gene expression and translocation was examined via immunohistochemistry and quantitative real-time polymerase chain reaction. Insulin signaling was studied by Western blot. Islets from taurine-supplemented mice had: (i) significantly higher insulin content, (ii) increased insulin secretion at stimulatory glucose concentrations, (iii) significantly displaced the dose-response curve for glucose-induced insulin release to the left, (iv) increased glucose metabolism at 5.6 and 11.1-mmol/L concentrations; (v) slowed cytosolic Ca2+ concentration ([Ca2+]i) oscillations in response to stimulatory glucose concentrations; (vi) increased insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression in the nucleus. Moreover, taurine supplementation significantly increased both basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an improved IPGTT. These results indicate that taurine controls glucose homeostasis by regulating the expression of genes required for glucose-stimulated insulin secretion. In addition, taurine enhances peripheral insulin sensitivity.

  15. Involvement of Nuclear Factor κB, not Pregnane X Receptor, in Inflammation-Mediated Regulation of Hepatic Transporters.

    PubMed

    Abualsunun, Walaa A; Piquette-Miller, Micheline

    2017-10-01

    Endotoxin-induced inflammation decreases the hepatic expression of several drug transporters, metabolizing enzymes, and nuclear transcription factors, including pregnane X receptor (PXR). As the nuclear factor κB (NF-κB) is a major mediator of inflammation, and reciprocal repression between NF-κB and PXR signaling has been reported, the objective of this study was to examine whether NF-κB directly regulates the expression of transporters or exerts its effect indirectly via PXR. PXR-deficient (-/-) or wild-type (+/+) male mice were dosed with the selective NF-κB inhibitor PHA408 (40 mg/kg i.p.) or vehicle (n = 5-8/group), followed by endotoxin (5 mg/kg) or saline 30 minutes later. Animals were sacrificed at 6 hours; samples were analyzed using quantitative reverse-transcription polymerase chain reaction and Western blots. Endotoxin induced tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and inducible nitric oxide synthase in PXR (+/+) and (-/-) mice. As compared with saline controls, endotoxin administration imposed 30%-70% significant decreases in the expression of Abcb1a, Abcb11, Abcc2, Abcc3, Abcg2, Slc10a1, Slco2b1, and Slco1a4 in PXR (+/+) and (-/-) mice to a similar extent. Preadministration of PHA408 attenuated endotoxin-mediated changes in both PXR (+/+) and (-/-) mice (P < 0.05). Our findings demonstrate that endotoxin activates NF-κB and imposes a downregulation of numerous ATP-binding cassette and solute carrier transporters through NF-κB in liver and is independent of PXR. Moreover, inhibition of NF-κB attenuates the impact of endotoxin on transporter expression. As NF-κB activation is involved in many acute and chronic disease states, disease-induced changes in transporter function may be an important source of variability in drug response. This information may be useful in predicting potential drug-disease interactions. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Hepatocyte divalent metal-ion transporter-1 is dispensable for hepatic iron accumulation and non-transferrin-bound iron uptake in mice

    PubMed Central

    Wang, Chia-Yu; Knutson, Mitchell D.

    2015-01-01

    Divalent metal-ion transporter-1 (DMT1) is required for iron uptake by the intestine and developing erythroid cells. DMT1 is also present in the liver, where it has been implicated in the uptake of transferrin-bound iron (TBI) and non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. To test the hypothesis that DMT1 is required for hepatic iron uptake, we examined mice with the Dmt1 gene selectively inactivated in hepatocytes (Dmt1liv/liv). We found that Dmt1liv/liv mice and controls (Dmt1flox/flox) did not differ in terms of hepatic iron concentrations or other parameters of iron status. To determine if hepatocyte DMT1 is required for hepatic iron accumulation, we crossed Dmt1liv/liv mice with Hfe−/− and hypotransferrinemic (Trfhpx/hpx) mice that develop hepatic iron overload. Double-mutant Hfe−/−;Dmt1liv/liv and Trfhpx/hpx;Dmt1liv/liv mice were found to accumulate similar amounts of hepatic iron as did their respective controls. To directly assess the role of DMT1 in NTBI and TBI uptake, we injected 59Fe-labeled ferric citrate (for NTBI) or 59Fe-transferrin into the plasma of Dmt1liv/liv and Dmt1flox/flox mice and measured the uptake of 59Fe by the liver. Dmt1liv/liv mice displayed no impairment of hepatic NTBI uptake, but TBI uptake was 40% lower. Hepatic levels of transferrin receptors 1 and 2 and ZIP14 (ZRT/IRT-like protein 14), which may also participate in iron uptake, were unaffected in Dmt1liv/liv mice. Additionally, liver iron levels were unaffected in Dmt1liv/liv mice fed an iron-deficient diet. Conclusion Hepatocyte DMT1 is dispensable for hepatic iron accumulation and NTBI uptake. Although hepatocyte DMT1 is partially required for hepatic TBI uptake, hepatic iron levels were unaffected in Dmt1liv/liv mice, suggesting that this pathway is a minor contributor to the iron economy of the liver. PMID:23508576

  17. mTOR ensures increased release and reduced uptake of the organic osmolyte taurine under hypoosmotic conditions in mouse fibroblasts.

    PubMed

    Lambert, Ian Henry; Jensen, Jane Vendelbo; Pedersen, Per Amstrup

    2014-06-01

    Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that modulates translation in response to growth factors and alterations in nutrient availability following hypoxia and DNA damage. Here we demonstrate that mTOR activity in Ehrlich Lettré ascites (ELA) cells is transiently increased within minutes following osmotic cell swelling and that inhibition of phosphatidylinositol-3-phosphatase (PTEN) counteracts the upstream phosphatidylinositol kinase and potentiates mTOR activity. PTEN inhibition concomitantly potentiates swelling-induced taurine release via the volume-sensitive transporter for organic osmolytes and anion channels (VSOAC) and enhances swelling-induced inhibition of taurine uptake via the taurine-specific transporter (TauT). Chronic osmotic stress, i.e., exposure to hypotonic or hypertonic media for 24 h, reduces and increases mTOR activity in ELA cells, respectively. Using rapamycin, we demonstrate that mTOR inhibition is accompanied by reduction in TauT activity and increase in VSOAC activity in cells expressing high (NIH3T3 fibroblasts) or low (ELA) amounts of mTOR protein. The effect of mTOR inhibition on TauT activity reflects reduced TauT mRNA, TauT protein abundance, and an overall reduction in protein synthesis, whereas the effect on VSOAC is mimicked by catalase inhibition and correlates with reduced catalase mRNA abundance. Hence, mTOR activity favors loss of taurine following hypoosmotic cell swelling, i.e., release via VSOAC and uptake via TauT during acute hypotonic exposure is potentiated and reduced, respectively, by phosphorylation involving mTOR and/or the kinases upstream to mTOR. Decrease in TauT activity during chronic hypotonic exposure, on the other hand, involves reduction in expression/activity of TauT and enzymes in antioxidative defense. Copyright © 2014 the American Physiological Society.

  18. Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats.

    PubMed

    Chen, Vincent Chin-Hung; Hsu, Tsai-Ching; Chen, Li-Jeng; Chou, Hong-Chun; Weng, Jun-Cheng; Tzang, Bor-Show

    2017-01-01

    Attention deficit hyperactivity disorder (ADHD) is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted. Significantly decreased serum C-reactive protein (CRP) was detected in rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased interleukin (IL)-1β and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats.

  19. Effects of taurine on anxiety-like and locomotor behavior of mice.

    PubMed

    El Idrissi, Abdeslem; Boukarrou, Latifa; Heany, Wally; Malliaros, George; Sangdee, Chaichan; Neuwirth, Lorenz

    2009-01-01

    Taurine is one of the most abundant free amino acids especially in excitable tissues, with wide physiological actions. We have previously reported that chronic supplementation of taurine in drinking water to mice increases brain excitability, mainly through alterations in the inhibitory GABAergic system. In this study we investigated the effects of chronic versus acute taurine treatment on anxiety-like and locomotor behaviors using two behavioral tests: elevated plus-maze and open-field. These two test conditions generated different levels of anxiety, and both anxiolytic and anxiogenic effects of taurine could be assessed. We used two paradigms for taurine treatment: Acute injection versus chronic supplementation. In the open field test, taurine supplementation increased whereas taurine injection suppressed locomotor activity. We found that taurine supplementation induced an increase in the total distance traveled, the overall movement speed, the time the animals spent mobile, the number of line crossings, and the time the animals entered the center zone. In the elevated arm maze, taurine injection suppressed anxiety whereas taurine supplementation was anxiogenic. The major findings of this are two folds: First these results suggest that taurine might play a role in the modulation of anxiety and locomotor activity. Second, taurine when injected acutely had opposite effects than when administered chronically.

  20. Kinetics of taurine depletion and repletion in plasma, serum, whole blood and skeletal muscle in cats.

    PubMed

    Pacioretty, L; Hickman, M A; Morris, J G; Rogers, Q R

    2001-12-01

    The relationship between taurine concentrations of plasma, whole blood, serum and skeletal muscle during taurine depletion and repletion was investigated in cats, to identify the most useful indicators of taurine status. Sixteen cats were fed a purified diet containing either 0 or 0.15 g/kg taurine for 5 months. Treatments were then reversed and the taurine concentration was measured during repletion and depletion phases. Plasma taurine exhibited the fastest rate (slow component) of depletion (t 1/2 = 4.8 wk), followed by serum (5.3 wk), whole blood (6.2 wk), and skeletal muscle (11.2 wk). Whole blood taurine was the first to replete at a rate of 0.74 wk to 1/2 maximal repletion, followed by serum (2.1 wk), skeletal muscle (3.5 wk), and plasma (3.5 wk). Whole blood more closely reflected skeletal muscle taurine concentrations than plasma during depletion, while plasma taurine concentrations appear to be the most valuable predictor of skeletal muscle taurine concentrations during repletion. This study suggests that the best clinical method to evaluate the taurine status of the cat is the determination and interpretation of both plasma and whole blood taurine concentrations.

  1. Differences in Mouse Hepatic Thyroid Hormone Transporter Expression with Age and Hyperthyroidism

    PubMed Central

    Engels, Kathrin; Rakov, Helena; Zwanziger, Denise; Moeller, Lars C.; Homuth, Georg; Köhrle, Josef; Brix, Klaudia; Führer, Dagmar

    2015-01-01

    Background Clinical features of thyroid dysfunction vary with age, and an oligosymptomatic presentation of hyperthyroidism is frequently observed in the elderly. This suggests age modulation of thyroid hormone (TH) action, which may occur, for example, by alterations in TH production, metabolism and/or TH action in target organs. Objectives: In this paper, we address possible changes in TH transporter expression in liver tissues as a mechanism of age-dependent variation in TH action. Methods Chronic hyperthyroidism was induced in 4- and 20-month-old C57BL6/NTac male mice (n = 8-10) by intraperitoneal injections of 1 µg/g body weight L-thyroxine (T4) every 48 h over 7 weeks. Control animals were injected with PBS. Total RNA was isolated from liver samples for analysis of the TH transporter and TH-responsive gene expression. TH concentrations were determined in mice sera. Results Baseline serum free T4 (fT4) concentrations were significantly higher in euthyroid young compared to old mice. T4 treatment increased total T4, fT4 and free triiodothyronine to comparable concentrations in young and old mice. In the euthyroid state, TH transporter expression was significantly higher in old than in young mice, except for Mct8 and Oatp1a1 expression levels. Hyperthyroidism resulted in upregulation of Mct10, Lat1 and Lat2 in liver tissue, while Oatp1a1, Oatp1b2 and Oatp1a4 expression was downregulated. This effect was preserved in old animals. Conclusion Here, we show age-dependent differences in TH transporter mRNA expression in the euthyroid and hyperthyroid state of mice focusing on the liver as a classical TH target organ. PMID:26601077

  2. Is Taurine a Biomarker in Autistic Spectrum Disorder?

    PubMed

    Park, Eunkyue; Cohen, Ira; Gonzalez, Maripaz; Castellano, Mario R; Flory, Michael; Jenkins, Edmund C; Brown, W Ted; Schuller-Levis, Georgia

    2017-01-01

    Taurine is a sulfur-containing amino acid which is not incorporated into protein. However, taurine has various critical physiological functions including development of the eye and brain, reproduction, osmoregulation, and immune functions including anti-inflammatory as well as anti-oxidant activity. The causes of autistic spectrum disorder (ASD) are not clear but a high heritability implicates an important role for genetic factors. Reports also implicate oxidative stress and inflammation in the etiology of ASD. Thus, taurine, a well-known antioxidant and regulator of inflammation, was investigated here using the sera from both girls and boys with ASD as well as their siblings and parents. Previous reports regarding taurine serum concentrations in ASD from various laboratories have been controversial. To address the potential role of taurine in ASD, we collected sera from 66 children with ASD (males: 45; females: 21, age 1.5-11.5 years, average age 5.2 ± 1.6) as well as their unaffected siblings (brothers: 24; sisters: 32, age 1.5-17 years, average age 7.0 ± 2.0) as controls of the children with ASD along with parents (fathers: 49; mothers: 54, age 28-45 years). The sera from normal adult controls (males: 47; females: 51, age 28-48 years) were used as controls for the parents. Taurine concentrations in all sera samples were measured using high performance liquid chromatography (HPLC) using a phenylisothiocyanate labeling technique. Taurine concentrations from female and male children with ASD were 123.8 ± 15.2 and 145.8 ± 8.1 μM, respectively, and those from their unaffected brothers and sisters were 142.6 ± 10.4 and 150.8 ± 8.4 μM, respectively. There was no significant difference in taurine concentration between autistic children and their unaffected siblings. Taurine concentrations in children with ASD were also not significantly different from their parents (mothers: 139.6 ± 7.7 μM, fathers: 147.4 ± 7.5 μM). No significant

  3. Perinatal taurine exposure affects adult arterial pressure control

    PubMed Central

    Roysommuti, Sanya; Wyss, J. Michael

    2012-01-01

    Taurine is an abundant free amino acid found in mammalian cells that contributes to many physiologic functions from that of a simple cell osmolyte to a programmer of adult health and disease. Taurine’s contribution extends from conception throughout life, but its most critical exposure period is during perinatal life. In adults, taurine supplementation prevents or alleviates cardiovascular disease and related complications. In contrast, low taurine consumption coincides with increased risk of cardiovascular disease, obesity and type II diabetes. This review focuses on the effects that altered perinatal taurine exposure has on long-term mechanisms that control adult arterial blood pressure and could thereby contribute to arterial hypertension through its ability to program these cardiovascular regulatory mechanisms very early in life. The modifications of these mechanisms can last a lifetime and transfer to the next generation, suggesting that epigenetic mechanisms underlie the changes. The ability of perinatal taurine exposure to influence arterial pressure control mechanisms and hypertension in adult life appears to involve the regulation of growth and development, the central and autonomic nervous system, the renin-angiotensin system, glucose-insulin interaction and changes to heart, blood vessels and kidney function. PMID:23070226

  4. Taurine levels and localisation in the stratified squamous epithelia.

    PubMed

    Lobo, M V; Alonso, F J; Latorre, A; Martín del Río, R

    2001-04-01

    The content and distribution of the amino acid taurine in squamous epithelia were studied using high-performance liquid chromatography and immunohistochemical methods. Quantitative analysis demonstrated that taurine was highly concentrated in the epidermis (5.49 mumol/g fresh tissue in the hairless skin of the hind footpad of the rat), although the values in the isolated stratum corneum were extremely low (< 0.073 mumol/g in the horny layer of the same skin area). No other analysed amino acid (such as glutamate, glutamine, glycine or alanine) showed this specific pattern of distribution. The immunohistochemical study revealed that in the dog and rat epidermis, taurine was present in the keratinocytes of the granular and upper spinous layers. The basal layer, lower spinous layer and stratum corneum were immunonegative. A similar immunostaining pattern was found in the epithelia of the different organs studied: the mouth, tongue and oesophagus of the dog and rat, the rat forestomach and the rat corneal epithelium. Other cell types, such as sebaceous and muscle cells, were immunolabelled. The existence of a circulating pool of taurine in the epidermis (via taurine release from keratinocytes before they reach the horny layer and its uptake by nearby cells) and its possible roles in these cells are discussed.

  5. Taurine improves learning and retention in aged mice.

    PubMed

    El Idrissi, Abdeslem

    2008-05-02

    Aging of the brain is characterized by several neurochemical modifications involving structural proteins, neurotransmitters, neuropeptides and related receptors. Alterations of neurochemical indices of synaptic function have been considered as indicators of age-related impairment of central functions, such as locomotion, memory and sensory performances. Several studies demonstrated that GABA receptors, glutamic acid decarboxylase (GAD65&67), and different subpopulations of GABAergic neurons are markedly decreased in experimental animal brains during aging. Thus, the age-related decline in cognitive functions could be attributable, at least in part, to decrements in GABA inhibitory neurotransmission. In this study, using a passive avoidance test, we show that chronic supplementation of taurine to aged mice significantly ameliorates the age-dependent decline in memory acquisition and retention. We have previously shown that taurine supplementation caused changes in the GABAergic system. These changes include increased levels of the neurotransmitters GABA and glutamate, increased expression of glutamic acid decarboxylase and the neuropeptide somatostatin and increase in the number of somatostatin-positive neurons. These specific alterations of the inhibitory system caused by taurine treatment oppose those naturally occurring in aging, and suggest a protective role of taurine against the normal aging process. Increased understanding of age-related neurochemical changes in the GABAergic system will be important in elucidating the underpinnings of the functional changes of aging. Taurine might help forestall the age-related decline in cognitive functions through alterations of the GABAergic system.

  6. Serum serotonin reduced the expression of hepatic transporter Mrp2 and P-gp via regulating nuclear receptor CAR in PI-IBS rats.

    PubMed

    Shao, Yun-Yun; Huang, Jing; Ma, Yan-Rong; Han, Miao; Ma, Kang; Qin, Hong-Yan; Rao, Zhi; Wu, Xin-An

    2015-08-01

    Hepatic transporters and drug metabolizing enzymes (DMEs) play important roles in the pharmacological effects and (or) side-effects of many drugs, and are regulated by several mediators, including neurotransmitters. This work aimed to investigate whether serum levels of 5-hydroxytryptamine (5-HT) affected the expression of hepatic transporters or DMEs. The expression of hepatic transporters was assessed using the Western-blot technique in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of post-infectious irritable bowel syndrome (PI-IBS), in which serum levels of 5-HT were significantly elevated. To further clarify the underlying mechanism, the 5-HT precursor 5-hydroxytryptophan (5-HTP) and the 5-HT depleting agent parachlorophenylalanine (pCPA) were applied to adjust serum levels of 5-HT. Serum levels of 5-HT were measured using LC-MS/MS; the expression of hepatic transporters, DMEs, and nuclear receptors were examined by Western-blot technique. Our results showed that in PI-IBS rats the expression of multidrug resistance protein 2 (Mrp2) was significantly decreased, while colonic enterochromaffin cell density and serum levels of 5-HT were all significantly increased. Moreover, 5-HTP treatment significantly increased serum levels of 5-HT and decreased the expression of Mrp2 and glycoprotein P (P-gp), whereas treatment with pCPA markedly decreased serum levels of 5-HT and increased the expression of Mrp2 and P-gp. Our results indicated that serum 5-HT regulates the expression of Mrp2 and P-gp, and the underlying mechanism may be related to the altered expression of the nuclear receptor constitutive androstane receptor (CAR).

  7. Effect of cholestasis on hepatic transport of /sup 99m/technetium p-isopropyl-iminodiacetic acid

    SciTech Connect

    Knodell, R.G.; Shafer, R.B.; Stanley, L.N.; Goodman, M.; Elson, M.K.

    1984-10-01

    Hepatobiliary imaging with /sup 99m/Tc-p-isopropyl-iminodiacetic acid (PIPIDA) and other acetanilidoiminodiacetic acid derivatives is a frequently used clinical tool in evaluating patients with jaundice. However, there has been little objective assessment of the effects of cholestasis on hepatic transport of acetanilioiminodiacetic acid derivatives. In our studies, transport of /sup 99m/Tc-PIPIDA by isolated rat hepatocytes obtained from animals with extrahepatic obstruction secondary to bile duct ligation or intrahepatic cholestasis induced by ethinyl estradiol therapy was determined. Uptake constants for /sup 99m/Tc-PIPIDA by hepatocytes isolated from livers of animals with ligated bile ducts were significantly decreased compared with uptake by liver cells from sham-operated controls (0.0030 +/- 0.0003 vs. 0.0089 +/- 0.0010 femtomole X 10(6) cells-1 X min-1 X pmol/L-1; p less than 0.001). Hepatocytes isolated from livers of animals given ethinyl estradiol also demonstrated significantly reduced /sup 99m/Tc-PIPIDA uptake compared with controls given propylene glycol (0.0034 +/- 0.0002 vs. 0.0060 +/- 0.0004 fmol X 10(6) cells-1 X min-1 X pmol/L-1; p less than 0.001). Fractional rates of efflux of the study compound from hepatocytes preincubated with /sup 99m/Tc-PIPIDA were significantly decreased in experiments using ethinyl estradiol (p less than 0.005) but did not differ significantly from controls in studies of bile duct ligation. /sup 99m/Tc-PIPIDA uptake was significantly decreased in the presence of high bile salt concentrations (100 to 200 mumol/L), but unconjugated bilirubin concentrations as high as 200 mumol/L (approximately 12 mg/dl) had no effect on hepatocyte uptake of the ligand.

  8. Thiol-disulfide effects on hepatic glutathione transport. Studies in cultured rat hepatocytes and perfused livers.

    PubMed Central

    Lu, S C; Ge, J L; Huang, H Y; Kuhlenkamp, J; Kaplowitz, N

    1993-01-01

    In cultured rat hepatocytes, cystine led to an inhibition of GSH efflux by lowering the Vmax by approximately 35% without affecting the Km. The cystine-mediated inhibition of GSH efflux was rapid in onset (< 1 h), with near maximum effect at 0.1 mM. Inhibition was still observed when cystine uptake was prevented. Cystine and sulfobromophthalein-GSH, a selective inhibitor of sinusoidal transport of GSH, did not exhibit additive inhibitory effects on GSH efflux. Depletion of ATP or membrane depolarization after cystine treatment were excluded as potential mechanisms. DTT not only reversed the cystine-mediated inhibition of GSH efflux, it stimulated GSH efflux up to 400-500%. The DTT effect was immediate in onset, reaching maximum after 30 min, and was partially reversed by cystine, suggesting that the two share a common site(s) of action. DTT treatment did not alter cellular ATP levels or change the membrane potential. In cultured hepatocytes, DTT treatment increased the Vmax of GSH efflux by approximately 500% without affecting the Km. Inhibition of microtubular function and vesicular acidification did not affect basal or DTT stimulated efflux. Both cystine and DTT effects on sinusoidal GSH efflux were confirmed in perfused livers. In summary, the capacity of the sinusoidal GSH transporter is markedly influenced by thiol-disulfide status. Images PMID:8376579

  9. Liver membrane composition after short-term parenteral nutrition with and without taurine in guinea pigs: the effect to taurine.

    PubMed

    Guertin, F; Roy, C C; Lepage, G; Yousef, I; Tuchweber, B

    1993-09-01

    Having recently demonstrated that taurine supplementation prevents total parenteral nutrition (TPN)-induced cholestasis, we chose to use this model to examine plasma membrane composition in relation to bile formation. Male guinea pigs received daily a mixture of glucose and of the amino acid solution Travasol with or without added taurine (1.2 mM). After 3 days, bile was collected and liver plasma membrane fractions enriched in sinusoidal lateral membrane and bile canalicular membrane domains were isolated. In animals receiving TPN alone, bile flow and biliary secretory rate of bile acid and bicarbonate decreased significantly compared with controls. Although membrane ATPases (Na+K+ and Mg+) were unchanged, TPN induced an increase in the lipid to protein ratio and a decrease of polyunsaturated fatty acids, in conjunction with a higher content of diene conjugates in sinusoidal lateral membrane fractions. Taurine corrected these changes and, in addition, reduced significantly the cholesterol to phospholipid ratio in both membrane fractions. The data show that changes in liver cell membranes occur in TPN-induced cholestasis and suggest that free radical injury may play a role. As taurine prevented cholestasis as well as membrane changes, it is suggested that taurine should be added to amino acid solutions used for parenteral nutrition.

  10. Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis.

    PubMed

    Stieger, Bruno; Geier, Andreas

    2011-04-01

    Drug-induced cholestasis, intrahepatic cholestasis of pregnancy and viral hepatitis are acquired forms of liver disease. Cholestasis is a pathophysiologic state with impaired bile formation and subsequent accumulation of bile salts in hepatocytes. The bile salt export pump (BSEP) (ABCB11) is the key export system for bile salts from hepatocytes. This article provides an introduction into the physiology of bile formation followed by a summary of the current knowledge on the key bile salt transporters, namely, the sodium-taurocholate co-transporting polypeptide NTCP, the organic anion transporting polypeptides (OATPs), BSEP and the multi-drug resistance protein 3. The pathophysiologic consequences of altered functions of these transporters, with an emphasis on molecular and genetic aspects, are then discussed. Knowledge of the role of hepatocellullar transporters, especially BSEP, in acquired cholestasis is continuously increasing. A common variant of BSEP (p.V444A) is now a well-established susceptibility factor for acquired cholestasis and recent evidence suggests that the same variant also influences the therapeutic response and disease progression of viral hepatitis C. Studies in large independent cohorts are now needed to confirm the relevance of p.V444A. Genome-wide association studies should lead to the identification of additional genetic factors underlying cholestatic liver disease.

  11. Role of GABAA and GABAB receptors and peripheral cholinergic mechanisms in the antinociceptive action of taurine.

    PubMed

    Serrano, M I; Serrano, J S; Guerrero, M R; Fernández, A

    1994-10-01

    1. Gabaergic and cholinergic mediation in the antinociceptive effect of taurine has been investigated in mice (acetic acid test) and rats (tail-flick test). 2. Scopolamine sulfate and methylnitrate exhibit intrinsic antinociceptive activity and increase the effect of taurine in mice. 3. Baclofen also increases the antinociceptive effect of taurine in mice. 4. Anticholinergic agents and bicuculline but not CGP 35348 antagonize the effect of taurine in rats. 5. These results suggest that the antinociceptive effect of taurine may be partly mediated by spinal GABAA receptors and peripheral cholinergic mechanisms.

  12. Changes in plasma taurine levels after different endurance events.

    PubMed

    Ward, R J; Francaux, M; Cuisinier, C; Sturbois, X; De Witte, P

    1999-01-01

    The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2 km and a 100 km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is performed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.

  13. Dilated cardiomyopathy in an American cocker spaniel with taurine deficiency.

    PubMed

    Gavaghan, B J; Kittleson, M D

    1997-12-01

    An American Cocker Spaniel with low plasma taurine concentration (< 2 nmol/mL) was presented with dyspnoea associated with pulmonary oedema and a left ventricular shortening fraction of 9%. Emergency therapy with furosemide, dobutamine, nitroglycerine and oxygen supplementation led to a good response. Chronic therapy was started with enalapril, furosemide, digoxin and taurine. Improvement in all echocardiographic indices were noted over a 22 week follow-up, most notably an increase in left ventricular shortening fraction to 20%, a decrease of E-point septal separation from 14 mm to 7 mm and marked left ventricular remodelling. This degree of improvement in myocardial function may represent a direct link between dilated cardiomyopathy in the American Cocker Spaniel and plasma taurine deficiency. Alternatively, this response may reflect a breed-related cardiomyopathy with a natural history and therapeutic response not commonly seen in the more common large breed cardiomyopathy presentations.

  14. [MITOCHONDRIA RESPIRATION AND OXIDATIVE PHOSPHORILATION OF RAT TISSUES AT TAURINE PER ORAL INJECTION].

    PubMed

    Ostapiv, R D; Manko, V V

    2015-01-01

    Taurine--sulphur-containing amino acid is a necessary component of mitochondrial matrix, where it maintains pH and is included in mitochondrial transport RNA. But still it is unclear how taurine influences on ATP synthesis and mitochondrial respiration chain components activity. Thus, the aim of the work was to study the effect of long-term per oral taurine injection on mitochondrial respiration intensity in rat tissues: liver, brain, testes and thigh muscle. For this purpose male Wistar rats, that weighted 190-220 g, were divided in three groups, daily during 28 days they were injected drinking water (control group) or taurine solution 40 and 100 mg per kg of body weight (I and II research groups, correspondingly). Respiration intensity was measured polarogrifically with use of Clark electrode at endogenic substrates oxidation (V₁), with exogenic α-ketoglutarate (5 mmol/l) or succinate (1 mmol/l;V₄S) addition, at ADP addition to concentration 200 µmol/l (V₃), and after ADP depletion (V₄ATP). Phosphorylation time, oxidative phosphorilation efficacy (ADP/O), respiratory controls by Lardy (V₃/V₄S) and Chance (V₃/V₄ATP) were calculated. It was found that long term taurine injection increased V₁ in animal brain and liver of both research groups, but it decreased in testes and muscles of I research group. In liver of I research group animals, when both α-ketoglutarate and succinate were oxidated, V₄S, V₃ and V₄ATP were 4-7 times larger than in control. At the same time, Lardy respiratory control increased at succinate oxidation, this may indirectly point on increased coupling between respiration and oxidative phosphorylation. In liver of II research group animals V₄S, V₃ and V₄/ATP when α-ketoglutarate was oxidated were significantly higher than in control. In muscles of I research group V₄S, V₃ and V₄ATP when α-ketoglutarate and succinate was added were lower than in control. In thigh muscle of II research group animals at

  15. Taurine increases testicular function in aged rats by inhibiting oxidative stress and apoptosis.

    PubMed

    Yang, Jiancheng; Zong, Xiaomeng; Wu, Gaofeng; Lin, Shumei; Feng, Ying; Hu, Jianmin

    2015-08-01

    In males, the decline of androgen synthesis, spermatogenesis and sexual function are the main phenotypes of aging, which may be attributed to testicular dysfunction. Taurine can act as an antioxidant, a testosterone secretion stimulator, a sperm membrane stabilizer and motility factor, and an anti-apoptotic agent. Recent observational studies suggested that taurine may play an important role in spermatogenesis, but to date whether taurine has anti-aging effects on testes remains unknown. We found that in aged rats testicular SDH and G6PDH activities, marker enzymes of testes, serum testosterone, testicular 3β-HSD and 17β-HSD mRNA expression levels were significantly increased by taurine treatment. Taurine administration also markedly raised the sperm count, viability and motility, decreased the sperm abnormality. Our data suggested that taurine can postpone testicular function deterioration in aged rats. Importantly, we observed obvious elevation of testicular antioxidant enzymes (SOD, GSH, GSH-Px) activities, and remarkable reduction of ROS and MDA by taurine administration, indicating taurine can decrease testicular oxidative stress and lipid peroxidation in aged rats. Finally, we found taurine effectively reduced testicular DNA fragmentation, increased testicular Bcl-2 protein expression, and decreased cytochrome c, Bax, Fas, FasL and caspase-3 expression, suggesting taurine can prohibit aged testicular apoptosis by mitochondrial dependent and independent signal pathway. In summary, our results indicated that taurine can suppress testicular function deterioration by increasing antioxidant ability and inhibiting apoptosis.

  16. Phototrophic utilization of taurine by the purple nonsulfur bacteria Rhodopseudomonas palustris and Rhodobacter sphaeroides.

    PubMed

    Novak, Ryan T; Gritzer, Rachel F; Leadbetter, Edward R; Godchaux, Walter

    2004-06-01

    Taurine metabolism by two phototrophically grown purple nonsulfur bacteria enrichment isolates has been examined. Rhodopseudomonas palustris (strain Tau1) grows with taurine as a sole electron donor, sulfur and nitrogen source during photoautotrophic growth. Rhodobacter sphaeroides (strain Tau3) grows on the compound as sole electron donor, sulfur and nitrogen source, and partial carbon source, in the presence of CO(2) during photoheterotrophic growth. Both organisms utilize an inducible taurine-pyruvate aminotransferase and a sulfoacetaldehyde acetyltransferase. The products of this metabolism are bisulfite and acetyl phosphate. Bisulfite ultimately was oxidized to sulfate, but this was not an adequate source of electrons for photometabolism. Experiments using either [U-(14)C]taurine or (14)CO(2) demonstrated that Rb. sphaeroides Tau3 assimilated the carbon from approximately equimolar amounts of taurine and exogenous CO(2). The taurine-carbon assimilation was not diminished by excess non-radioactive bicarbonate. Malate synthase (but not isocitrate lyase) was induced in these taurine-grown cells. It is concluded that assimilation of taurine carbon occurs through an intermediate other than CO(2). Similar labelling experiments with Rp. palustris Tau1 determined that taurine is utilized only as an electron donor for the reduction of CO(2), which contributes all the cell carbon. Photoautotrophic metabolism was confirmed in this organism by the absence of either malate synthase or isocitrate lyase in taurine+CO(2)-grown cells. Culture collection strains of these two bacteria did not utilize taurine in these fashions.

  17. Kinetics for the synthetic bile acid 75-selenohomocholic acid-taurine in humans: comparison with (/sup 14/C)taurocholate

    SciTech Connect

    Jazrawi, R.P.; Ferraris, R.; Bridges, C.; Northfield, T.C.

    1988-07-01

    The apparent fractional turnover rate of the gamma-labeled bile acid analogue 75-selenohomocholic acid-taurine (75-SeHCAT) was assessed from decline in radioactivity over the gallbladder area on 4 successive days using a gamma-camera, and was compared in the same subjects with the fractional turnover rate of the corresponding natural bile acid, cholic acid-taurine, labeled with 14C ((14C)CAT) using the classical Lindstedt technique. Very similar results were obtained in 5 healthy individuals (coefficient of variation 4.8%, medians 0.35 and 0.34, respectively). By contrast, the fractional deconjugation rate assessed from zonal scanning of glycine- and taurine-conjugated bile acids on thin-layer chromatography was much less for 75-SeHCAT than for (14C)CAT (0.02 and 0.13, respectively; p less than 0.05). The fractional rate for deconjugation plus dehydroxylation was also determined by zonal scanning, and gave lower values for 75-SeHCAT than for (14C)CAT (0.02 and 0.12, respectively; p less than 0.05). There was a striking similarity between the fractional rate for deconjugation alone and that for deconjugation plus dehydroxylation for both bile acids in individual samples (r = 0.999, p less than 0.001), suggesting that these two processes might occur simultaneously and probably involve the same bacteria. We conclude that our scintiscanning technique provides an accurate, noninvasive method of measuring fractional turnover rate of a bile acid in humans, and that the finding that 75SeHCAT remains conjugated with taurine during enterohepatic recycling means that absorption should be specific for the ileal active transport site, thus rendering it an ideal substance for assessing ileal function.

  18. Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats.

    PubMed

    Qian, Taizhe; Chen, Rongqing; Nakamura, Masato; Furukawa, Tomonori; Kumada, Tatsuro; Akita, Tenpei; Kilb, Werner; Luhmann, Heiko J; Nakahara, Daiichiro; Fukuda, Atsuo

    2014-01-01

    In the developing cerebral cortex, the marginal zone (MZ), consisting of early-generated neurons such as Cajal-Retzius cells, plays an important role in cell migration and lamination. There is accumulating evidence of widespread excitatory neurotransmission mediated by γ-aminobutyric acid (GABA) in the MZ. Cajal-Retzius cells express not only GABAA receptors but also α2/β subunits of glycine receptors, and exhibit glycine receptor-mediated depolarization due to high [Cl(-)]i. However, the physiological roles of glycine receptors and their endogenous agonists during neurotransmission in the MZ are yet to be elucidated. To address this question, we performed optical imaging from the MZ using the voltage-sensitive dye JPW1114 on tangential neocortical slices of neonatal rats. A single electrical stimulus evoked an action-potential-dependent optical signal that spread radially over the MZ. The amplitude of the signal was not affected by glutamate receptor blockers, but was suppressed by either GABAA or glycine receptor antagonists. Combined application of both antagonists nearly abolished the signal. Inhibition of Na(+), K(+)-2Cl(-) cotransporter by 20 µM bumetanide reduced the signal, indicating that this transporter contributes to excitation. Analysis of the interstitial fluid obtained by microdialysis from tangential neocortical slices with high-performance liquid chromatography revealed that GABA and taurine, but not glycine or glutamate, were released in the MZ in response to the electrical stimulation. The ambient release of taurine was reduced by the addition of a voltage-sensitive Na(+) channel blocker. Immunohistochemistry and immunoelectron microscopy indicated that taurine was stored both in Cajal-Retzius and non-Cajal-Retzius cells in the MZ, but was not localized in presynaptic structures. Our results suggest that activity-dependent non-synaptic release of endogenous taurine facilitates excitatory neurotransmission through activation of glycine

  19. The effect of 48-hour fasting on taurine status in healthy adult dogs.

    PubMed

    Gray, K; Alexander, L G; Staunton, R; Colyer, A; Watson, A; Fascetti, A J

    2016-06-01

    Low circulating taurine concentrations may be a risk factor for dilated cardiomyopathy (DCM) in dogs. Circulating taurine is typically measured in the clinic 4-5 h after feeding, largely because the impact of later sampling is not known. The objective of this study was to measure taurine in the blood during a 48-h fast in 12 healthy adult Labrador Retrievers to refine sampling methodology for determination of taurine status. Plasma and whole blood (WB) taurine concentrations did not fall to levels indicative of clinical deficiency throughout fasting; WB was the more reliable indicator of taurine status. This study shows that blood samples can be taken for assessment of taurine status any time up to 48 h after ingestion of a meal in healthy adult dogs. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  20. Effect of taurine on human fetal neuron cells: proliferation and differentiation.

    PubMed

    Chen, X C; Pan, Z L; Liu, D S; Han, X

    1998-01-01

    The purpose of this study was to investigate the effect of taurine on human fetal brain neuron cell proliferation and differentiation using a glial-free, pure cerebral neuronal culture grown in a serum-free environment. We found that taurine was necessary for neuronal survival and neurite extension. Taurine, on the other hand, has a trophic effect on the human fetal brain cell, promoting both proliferation and differentiation. Results showed that DNA synthesis of the neurons was increased in a dose-dependent manner when neurons were cultured in the medium containing taurine (100-6400 microM). The protein content of neuronal cells was also significantly increased in the neurons treated with taurine as compared to the control. At day 15, the expression of neuron-specific enolase (NSE) was only detected in the neurons cultured in the medium containing taurine. These results establish taurine as a putative human fetal brain neurontrophic factor in the process of human brain development.

  1. Antidiabetic effect of taurine in cultured rat skeletal l6 myotubes.

    PubMed

    Cheong, Sun Hee; Chang, Kyung Ja

    2013-01-01

    Taurine (2-aminoethanesulfonic acid), a sulfur-containing β-amino acid, is found in all animal cells at millimolar concentrations and has been reported to show various health promoting activities including antidiabetic properties. The beneficial effects of taurine in diabetes mellitus have been known. However, the exact mechanism of hypoglycemic action of taurine is not properly defined. In this study, we investigated antidiabetic effect of taurine in the cell culture system using rat skeletal muscle cells. In cultured rat skeletal L6 myotubes, we studied the effect of taurine (0-100 μM) on glucose uptake to plasma membrane from the aspects of AMP-activated protein kinase (AMPK) signaling. Taurine stimulated glucose uptake in a dose-dependent manner by activating AMPK signaling. From these results, it may suggest that taurine show antidiabetic effect by stimulating insulin-independent glucose uptake in rat skeletal muscle.

  2. Taurine activates glycine and gamma-aminobutyric acid A receptors in rat substantia gelatinosa neurons.

    PubMed

    Wu, Jun; Kohno, Tatsuro; Georgiev, Stefan K; Ikoma, Miho; Ishii, Hideaki; Petrenko, Andrey B; Baba, Hiroshi

    2008-02-12

    Taurine has been suggested to modulate nociceptive information at the spinal cord level. In this study, the pharmacological properties of taurine were investigated in adult rat substantia gelatinosa (SG) neurons using whole-cell patch-clamp method. We found that taurine seemed to have higher efficacy than glycine on glycine receptors in SG neurons. An increase in chloride conductance was responsible for taurine-induced currents. Taurine at 0.3 mM activated glycine receptors, whereas at 3 mM activated both glycine and gamma-aminobutyric acid A receptors. The currents activated by coapplication of taurine and glycine are cross inhibitive. Altogether these results show that taurine might represent another important neurotransmitter or modulator in SG neurons, which may be involved in antinociception.

  3. A karyopherin alpha2 nuclear transport pathway is regulated by glucose in hepatic and pancreatic cells.

    PubMed

    Cassany, Aurélia; Guillemain, Ghislaine; Klein, Christophe; Dalet, Véronique; Brot-Laroche, Edith; Leturque, Armelle

    2004-01-01

    We studied the role of the karyopherin alpha2 nuclear import carrier (also known as importin alpha2) in glucose signaling. In mhAT3F hepatoma cells, GFP-karyopherin alpha2 accumulated massively in the cytoplasm within minutes of glucose extracellular addition and returned to the nucleus after glucose removal. In contrast, GFP-karyopherin alpha1 distribution was unaffected regardless of glucose concentration. Glucose increased GFP-karyopherin alpha2 nuclear efflux by a factor 80 and its shuttling by a factor 4. These glucose-induced movements were not due to glycolytic ATP production. The mechanism involved was leptomycin B-insensitive, but phosphatase- and energy-dependent. HepG2 and COS-7 cells displayed no glucose-induced GFP-karyopherin alpha2 movements. In pancreatic MIN-6 cells, the glucose-induced movements of karyopherin alpha2 and the stimulation of glucose-induced gene transcription were simultaneously lost between passages 28 and 33. Thus, extracellular glucose regulates a nuclear transport pathway by increasing the nuclear efflux and shuttling of karyopherin alpha2 in cells in which glucose can stimulate the transcription of sugar-responsive genes.

  4. Determination of bilirubin by thermal lens spectrometry and studies of its transport into hepatic cells

    NASA Astrophysics Data System (ADS)

    Margon, A.; Terdoslavich, M.; Cocolo, A.; Decorti, G.; Passamonti, S.; Franko, M.

    2005-06-01

    The liver is responsible for clearance of bilirubin, the end product of heme catabolism, from the bloodstream. The main aim of our investigation was to determine the role of the carrier protein bilitranslocase in bilirubin uptake into the liver. Our experiments consisted of exposing cell cultures to bilirubin solutions under different conditions and measuring the uptake of bilirubin into the cells. However, since bilirubin is only slightly soluble in aqueous solution (< 70 nM at pH 7.4), we had to use bilirubin concentrations that are far below the limit of detection of the commonly used techniques (e.g. LOD for HPLC with UV-Vis detection \\cong 10 μM). TLS showed up to be a suitable technique for investigation of bilirubin uptake with an LOD of 2 nM. Under basal conditions, bilirubin uptake did not occur. However, increase of cytosolic NADH due to catabolism of specific substrates (e.g. lactate or ethanol) seemed to trigger bilirubin uptake. Furthermore, bilirubin uptake was completely inhibited by addition of specific anti-bilitranslocase antibodies. We can thus infer that, under these conditions, bilitranslocase is the main bilirubin transporter.

  5. Selective neuroinhibitory effects of taurine in slices of rat main olfactory bulb.

    PubMed

    Belluzzi, O; Puopolo, M; Benedusi, M; Kratskin, I

    2004-01-01

    Taurine is abundant in the main olfactory bulb, exceeding glutamate and GABA in concentration. In whole-cell patch-clamp recordings in rat olfactory bulb slices, taurine inhibited principal neurons, mitral and tufted cells. In these cells, taurine decreased the input resistance and caused a shift of the membrane potential toward the chloride equilibrium potential. The taurine actions were sustained under the blockade of transmitter release and were reversible and dose-dependent. At a concentration of 5 mM, typically used in this study, taurine showed 90% of its maximal effect. GABA(A) antagonists, bicuculline and picrotoxin, blocked the taurine actions, whereas the glycine receptor antagonist strychnine and GABA(B) antagonists, CGP 55845A and CGP 35348, were ineffective. These findings are consistent with taurine directly activating GABA(A) receptors and inducing chloride conductance. Taurine had no effect on periglomerular and granule interneurons. The subunit composition of GABA(A) receptors in these cells, differing from those in mitral and tufted cells, may account for taurine insensitivity of the interneurons. Taurine suppressed olfactory nerve-evoked monosynaptic responses of mitral and tufted cells while chloride conductance was blocked. This action was mimicked by the GABA(B) agonist baclofen and abolished by CGP 55845A; CGP 35348, which primarily blocks postsynaptic GABA(B) receptors, was ineffective. The taurine effect most likely was due to GABA(B) receptor-mediated inhibition of presynaptic glutamate release. Neither taurine nor baclofen affected responses of periglomerular cells. The lack of a baclofen effect implies that functional GABA(B) receptors are absent from olfactory nerve terminals that contact periglomerular cells. These results indicate that taurine decreases the excitability of mitral and tufted cells and their responses to olfactory nerve stimulation without influencing periglomerular and granule cells. Selective effects of taurine in the

  6. Non chromatographic colorimetric assay for total taurine-conjugated bile acids: application of measurements of glycine: taurine ratio in bile.

    PubMed

    Christie, W H; Macdonald, I A; Williams, C N

    1975-03-01

    A direct colorimetric assay for total conjugated taurine from bile-rich duodenal aspirates is described. The method is based on complete acetylation of the free hydroxyl groups by acetic anhydride at 100 degrees C. of both the tri- and di-hydroxy bile acids in Folch extracted bile samples. Taurine-conjugated bile acids are measured by ion pair formation with Azure A and subsequent extraction of the complex into the organic phase of a biphasic system. Absorption at 645 nm. of this complex directly quantifies total taurine-conjugated bile acid. Total bile acids are then estimated by the 3alpha-hydroxysteroid dehydrogenase assay. The difference between the concentration of the total conjugated bile acid and of the total conjugated taurine determines the concentration of glycine conjugates and the glycine:taurine ratio. Potentially interfering materials such as sulphalipids, certain phospholipids, and unconjugated bile acids are removed by Folch extraction. The 3-hydroxysteroid sulfates (cholesteryl sulfate, lithocholate sulfate, and glycocholate sulfate) are not measurable by heating in acetic anhydride and do not interfere. Taurolithocholate-3-sulfate, under identical conditions, gives a measurable but very low color yield and in normal physiologic concentrations would contribute negligible color. As previously reported, this assay under prescribed conditions is selective for long-chain amphipathic sulfates or sulfonates with no measurable color yield with glycine conjugates, unconjugated bile acids, free fatty acids, or lecithin. Values for glycine:taurine ratios by the above-described method in both normal bile extracts and extracts from patients with either elevated or depressed ratios relate closely to those determined by thin-layer chromatography.

  7. Penetration profile of taurine in the human skin and its distribution in skin layers.

    PubMed

    da Silva, D L P; Thiago, S B; Pessôa, F A; Mrestani, Y; Rüttinger, H H; Wohlrab, J; Neubert, R H H

    2008-08-01

    To measure in vitro release of taurine from a semisolid standard formulation (amphiphilic cream, DAC) containing 1% taurine, a multi-layer membrane system was used. The content and distribution of taurine in different healthy skin layers (stratum corneum, epidermis and dermis) before (native taurine) and after application of the DAC cream were determined using capillary electrophoresis. The release of taurine from the DAC cream was studied using a multilayer membrane system. Due to the high hydrophilic properties of taurine, the artificial model membranes consisted of collodion as matrix and glycerol as the acceptor phase. In order to determine whether taurine shows the potential for dermal penetration a Franz diffusion cell system was used. The distribution of taurine in the skin layers was determined before and after application of the DAC cream followed by the incubation in a Franz diffusion cell. The excised skin sample was cut in horizontal sections using a cryomicrotome. In order to detect taurine, fluorescamine was used as a derivatization agent. Experiments with a multilayer membrane system were performed to verify the release of taurine at different times (1, 2 and 5 h). Approximately 42.5% taurine was released from the semisolid standard formulation, accumulating in the first membrane (17.63%). The native taurine content was quantified in human isolated skin layer before and after the application of the semisolid standard formulation followed by incubation in a Franz-type diffusion cell for 1 and 5 h. No statistically significant difference (p < 0.05) of the taurine content in the skin layers existed between exposure times (1 and 5 h) studied. The highest taurine content was found in the epidermis both before (256.01 microg taurine/g skin layer) and after (555.5 microg taurine/g skin layer) the application of the DAC cream. The distribution profile of taurine in the skin layers was very similar for the times studied, which suggests that taurine is

  8. Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain

    PubMed Central

    Frosini, Maria; Sesti, Casilde; Dragoni, Stefania; Valoti, Massimo; Palmi, Mitri; Dixon, Henry B F; Machetti, Fabrizio; Sgaragli, Giampietro

    2003-01-01

    The aim of this study was to find taurinergic compounds that do not interact with brain GABA ergic systems. Washed synaptic membranes (SM) from whole rabbit brain were able to bind [3H]muscimol. Saturation experiments of the binding of [3H]GABA to GABAB receptors showed that SM possess two binding components; twice Triton X-100-treated SM contained 0.048 mmol endogenous taurine/kg protein and bound [3H]taurine in a saturable manner (Kd=249.0±6.3 nM and Bmax=3.4±1.0 pmol mg−1 prot). Among the 19 structural analogues of taurine, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (±)cis-2-aminocyclohexane sulfonic acids (CAHS) displaced [3H]taurine binding (Ki=0.13, 0.13, 13.5 and 4.0 μM, respectively). These analogues did not interact with GABAA and GABAB receptors and did not affect taurine- and GABA-uptake systems and GABA-transaminase activity. 3-Aminopropanesulfonic acid (OMO), β-alanine, pyridine-3-sulfonic acid, N,N,N-trimethyltaurine (TMT), 2-(guanidino)ethanesulfonic acid (GES), ethanolamine-O-sulphate, N,N-dimethyltaurine (DMT), taurine and (±)piperidine-3-sulfonic acid (PSA) inhibited [3H]muscimol binding to GABAA receptors with different affinities (Ki=0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 μM, respectively). Taurine, 2-aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [3H]GABA to GABAB receptors with Ki's in the μM range (0.8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC50=3.72 μM) and PSA GABA transaminase activity (IC50=103.0 μM). In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents. PMID:12684273

  9. Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain.

    PubMed

    Frosini, Maria; Sesti, Casilde; Dragoni, Stefania; Valoti, Massimo; Palmi, Mitri; Dixon, Henry B F; Machetti, Fabrizio; Sgaragli, Giampietro

    2003-03-01

    1. The aim of this study was to find taurinergic compounds that do not interact with brain GABA ergic systems. 2. Washed synaptic membranes (SM) from whole rabbit brain were able to bind [(3)H]muscimol. Saturation experiments of the binding of [(3)H]GABA to GABA(B) receptors showed that SM possess two binding components; twice Triton X-100-treated SM contained 0.048 mmol endogenous taurine/kg protein and bound [(3)H]taurine in a saturable manner (K(d)=249.0+/-6.3 nM and B(max)=3.4+/-1.0 pmol mg(-1) prot). 3. Among the 19 structural analogues of taurine, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (+/-)cis-2-aminocyclohexane sulfonic acids (CAHS) displaced [(3)H]taurine binding (K(i)=0.13, 0.13, 13.5 and 4.0 micro M, respectively). These analogues did not interact with GABA(A) and GABA(B) receptors and did not affect taurine- and GABA-uptake systems and GABA-transaminase activity. 4. 3-Aminopropanesulfonic acid (OMO), beta-alanine, pyridine-3-sulfonic acid, N,N,N-trimethyltaurine (TMT), 2-(guanidino)ethanesulfonic acid (GES), ethanolamine-O-sulphate, N,N-dimethyltaurine (DMT), taurine and (+/-)piperidine-3-sulfonic acid (PSA) inhibited [(3)H]muscimol binding to GABA(A) receptors with different affinities (K(i)=0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 micro M, respectively). Taurine, 2-aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [(3)H]GABA to GABA(B) receptors with K(i)'s in the micro M range (0.8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC(50)=3.72 micro M) and PSA GABA transaminase activity (IC(50)=103.0 micro M). 5. In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents.

  10. Hepatitis A

    MedlinePlus

    Hepatitis A Hepatitis A Hepatitis A is a contagious viral infection that can easily affect children and adults. It is one of the most common types of hepatitis virus. Often when you hear about hepatitis A ...

  11. MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor.

    PubMed

    de Aguiar Vallim, Thomas Q; Tarling, Elizabeth J; Kim, Tammy; Civelek, Mete; Baldán, Ángel; Esau, Christine; Edwards, Peter A

    2013-06-07

    The bile acid receptor farnesoid X receptor (FXR) regulates many aspects of lipid metabolism by variouscomplex and incompletely understood molecular mechanisms. We set out to investigate the molecular mechanisms for FXR-dependent regulation of lipid and lipoprotein metabolism. To identify FXR-regulated microRNAs that were subsequently involved in regulating lipid metabolism. ATP binding cassette transporter A1 (ABCA1) is a major determinant of plasma high-density lipoprotein (HDL)-cholesterol levels. Here, we show that activation of the nuclear receptor FXR in vivo increases hepatic levels of miR-144, which in turn lowers hepatic ABCA1 and plasma HDL levels. We identified 2 complementary sequences to miR-144 in the 3' untranslated region of ABCA1 mRNA that are necessary for miR-144-dependent regulation. Overexpression of miR-144 in vitro decreased both cellular ABCA1 protein and cholesterol efflux to lipid-poor apolipoprotein A-I protein, whereas overexpression in vivo reduced hepatic ABCA1 protein and plasma HDL-cholesterol. Conversely, silencing miR-144 in mice increased hepatic ABCA1 protein and HDL-cholesterol. In addition, we used tissue-specific FXR-deficient mice to show that induction of miR-144 and FXR-dependent hypolipidemia requires hepatic, but not intestinal, FXR. Finally, we identified functional FXR response elements upstream of the miR-144 locus, consistent with direct FXR regulation. We have identified a novel pathway involving FXR, miR-144, and ABCA1 that together regulate plasma HDL-cholesterol.

  12. Endogenous N-acyl taurines regulate skin wound healing

    PubMed Central

    Sasso, Oscar; Pontis, Silvia; Armirotti, Andrea; Cardinali, Giorgia; Kovacs, Daniela; Migliore, Marco; Summa, Maria; Moreno-Sanz, Guillermo; Picardo, Mauro; Piomelli, Daniele

    2016-01-01

    The intracellular serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived bioactive molecules that include amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)]. The physiological functions of the NATs are unknown. Here we show that genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and stimulates motogenesis of human keratinocytes and differentiation of human fibroblasts in primary cultures. Using untargeted and targeted lipidomics strategies, we identify two long-chain saturated NATs—N-tetracosanoyl-taurine [NAT(24:0)] and N-eicosanoyl-taurine [NAT(20:0)]—as primary substrates for FAAH in mouse skin, and show that the levels of these substances sharply decrease at the margins of a freshly inflicted wound to increase again as healing begins. Additionally, we demonstrate that local administration of synthetic NATs accelerates wound closure in mice and stimulates repair-associated responses in primary cultures of human keratinocytes and fibroblasts, through a mechanism that involves tyrosine phosphorylation of the epidermal growth factor receptor and an increase in intracellular calcium levels, under the permissive control of transient receptor potential vanilloid-1 receptors. The results point to FAAH-regulated NAT signaling as an unprecedented lipid-based mechanism of wound-healing control in mammalian skin, which might be targeted for chronic wound therapy. PMID:27412859

  13. Effects of taurine supplementation following eccentric exercise in young adults.

    PubMed

    da Silva, Luciano A; Tromm, Camila B; Bom, Karoline F; Mariano, Izadora; Pozzi, Bruna; da Rosa, Guilherme L; Tuon, Talita; da Luz, Gabrielle; Vuolo, Francilele; Petronilho, Fabricia; Cassiano, Willians; De Souza, Claudio T; Pinho, Ricardo Aurino

    2014-01-01

    The purpose of the present study was to investigate the effects of taurine supplementation on muscle performance, oxidative stress, and inflammation response after eccentric exercise (EE) in males. Twenty-one participants (mean age, 21 ± 6 years; weight, 78.2 ± 5 kg; height, 176 ± 7 cm) were selected and randomly divided into two groups: placebo (n = 10) and taurine (n = 11). Fourteen days after starting supplementation, subjects performed EE (3 sets until exhaustion, with EE of the elbow flexors on the Scott bench, 80% 1 repetition maximum (RM)). Blood samples were collected and muscle performance was measured on days 1, 14, 16, 18, and 21 after starting the supplements. Then, performance, muscle damage, oxidative stress, and inflammatory markers were analyzed. The taurine supplementation resulted in increased strength levels and thiol total content and decreased muscle soreness, lactate dehydrogenase level, creatine kinase activity, and oxidative damage (xylenol and protein carbonyl). Antioxidant enzymes (superoxide dismutase, catalase, and gluthatione peroxidase) and inflammatory markers (tumor necrosis factor, interleukin-1β (IL-1β), and interleukin-10 (IL-10)) were not altered during the recovery period compared with the placebo group. The results suggest that taurine supplementation represents an important factor in improving performance and decreasing muscle damage and oxidative stress but does not decrease the inflammatory response after EE.

  14. Occurrence of a taurine derivative in an antarctic glass sponge.

    PubMed

    Carbone, Marianna; Núñez-Pons, Laura; Ciavatta, M Letizia; Castelluccio, Francesco; Avila, Conxita; Gavagnin, Margherita

    2014-04-01

    The n-butanol extract of an Antarctic hexactinellid sponge, Anoxycalyx (Scolymastra) joubini, was found to contain a taurine-conjugated anthranilic acid, never reported so far either as a natural product or by synthesis. The compound was inactive against human cancer cells in an in vitro growth inhibitory test, and also showed no antibacterial activity.

  15. Identification of Endogenous Biomarkers to Predict the Propensity of Drug Candidates to Cause Hepatic or Renal Transporter-Mediated Drug-Drug Interactions.

    PubMed

    Chu, Xiaoyan; Chan, Grace Hoyee; Evers, Raymond

    2017-09-01

    Drug transporters expressed in liver and kidney play a critical role in the elimination of a wide range of drugs and xenobiotics and inhibition of these transporters may therefore cause clinically significant drug-drug interactions (DDIs). Currently, in vitro transporter inhibition data are used to assess the risk that a drug candidate may act as an inhibitor of a transporter in patients at clinically relevant exposures. However, this approach is hampered by low confidence in in vitro to in vivo extrapolations, and large inter-system and inter-laboratory variability in in vitro data. Several endogenous compounds have been identified as substrates of drug transporters. Determining the impact of perpetrator drugs on the plasma or urinary exposure of these potential endogenous biomarkers in humans is being explored as an alternative approach to assess the DDI liability of drug candidates, especially in early drug development. In this review, we provide an overview of recently identified biomarkers used to study the inhibition of hepatic and renal transporters; summarize the methods and strategies employed to identify biomarkers; and discuss the utility, limitation, and future direction of biomarker approaches to predict transporter-mediated DDIs. Copyright © 2017. Published by Elsevier Inc.

  16. Effects of taurine on cardiovascular and autonomic nervous functions in cold exposed rats.

    PubMed

    Kuwahara, Masayoshi; Kawaguchi, Tomohiro; Ito, Koichi; Tsubone, Hirokazu

    2009-01-01

    Exposure to cold temperature might affect on cardiovascular and autonomic nervous function. Although there are a lot of studies on physiological and pathophysiological responses of taurine, it was poorly understood the effects of taurine on cardiovascular and autonomic nervous function during cold circumstances. Therefore, the purpose of this study was to clarify the possible role of taurine on cardiovascular and autonomic nervous function in rats exposed to cold temperature. For this purpose, heart rate, blood pressure and locomotive activity were recorded from conscious and unrestrained rats using a telemetry system. Moreover, the autonomic nervous function was investigated by power spectral analysis of heart rate variability. After the recovery period of implantation of transmitter, 1% taurine was supplied during experimental period ad libitum. After the 7 days control period, both taurine administrated and control groups of rats were exposed a cold temperature. There were no differences in heart rate, blood pressure and locomotive activity between taurine and control groups before cold exposure. However, parasympathetic nervous function was somewhat predominant in taurine group. Heart rate and blood pressure in both groups increased greatly by cold exposure. Heart rate in taurine group was much higher than that in control group. LF and HF powers were decreased by cold exposure in both groups. Although no differences were observed in LF, decrease of HF in taurine group was greater than that in control group. These results suggested that taurine might provide some reservoir for cardiovascular and autonomic nervous function to cold stress in rats.

  17. Effect of taurine and caffeine on sleep-wake activity in Drosophila melanogaster.

    PubMed

    Lin, Fang Ju; Pierce, Michael M; Sehgal, Amita; Wu, Tianyi; Skipper, Daniel C; Chabba, Radhika

    2010-01-01

    Caffeine and taurine are two major neuromodulators present in large quantities in many popular energy drinks. We investigated their effects on sleep-wake control in constant darkness using the fruit fly Drosophila as a model system. It has been shown that caffeine, as the most widely used psychostimulant, can boost arousal through the dopamine pathway in the mushroom bodies of flies. Taurine is a GABA receptor agonist, which is inhibitory to neuronal firing. We show here that flies receiving a low dose of caffeine (0.01%) increase locomotor activity by 25%, and decrease total sleep by 15%. Treatment with taurine at 0.1% to 1.5% reduces locomotor activity by 28% to 86%, and shifts it from diurnal to nocturnal. At 0.75%, taurine also increases total sleep by 50%. Our results show that taurine increases sleep, while caffeine, as previously reported, attenuates sleep. Flies treated with both caffeine and taurine exhibit two differential effects which depend upon the ratio of taurine to caffeine. A high taurine:caffeine ratio promotes sleep, while a low ratio of taurine:caffeine inhibits sleep to a greater extent than the equivalent amount of caffeine alone. This intriguing enhancement of caffeine action by low doses of taurine may account for the presence of both compounds in energy-promoting drinks such as Red Bull® and Monster®.

  18. Partial agonism of taurine at gamma-containing native and recombinant GABAA receptors.

    PubMed

    Kletke, Olaf; Gisselmann, Guenter; May, Andrea; Hatt, Hanns; A Sergeeva, Olga

    2013-01-01

    Taurine is a semi-essential sulfonic acid found at high concentrations in plasma and mammalian tissues which regulates osmolarity, ion channel activity and glucose homeostasis. The structural requirements of GABAA-receptors (GABAAR) gated by taurine are not yet known. We determined taurine potency and efficacy relative to GABA at different types of recombinant GABAAR occurring in central histaminergic neurons of the mouse hypothalamic tuberomamillary nucleus (TMN) which controls arousal. At binary α(1/2)β(1/3) receptors taurine was as efficient as GABA, whereas incorporation of the γ(1/2) subunit reduced taurine efficacy to 60-90% of GABA. The mutation γ(2F77I), which abolishes zolpidem potentiation, significantly reduced taurine efficacy at recombinant and native receptors compared to the wild type controls. As taurine was a full- or super- agonist at recombinant αxβ1δ-GABAAR, we generated a chimeric γ(2) subunit carrying the δ subunit motif around F77 (MTVFLH). At α(1/2)β(1)γ2(MTVFLH) receptors taurine became a super-agonist, similar to δ-containing ternary receptors, but remained a partial agonist at β3-containing receptors. In conclusion, using site-directed mutagenesis we found structural determinants of taurine's partial agonism at γ-containing GABAA receptors. Our study sheds new light on the β1 subunit conferring the widest range of taurine-efficacies modifying GABAAR function under (patho)physiological conditions.

  19. Effect of taurine and caffeine on sleep–wake activity in Drosophila melanogaster

    PubMed Central

    Lin, Fang Ju; Pierce, Michael M; Sehgal, Amita; Wu, Tianyi; Skipper, Daniel C; Chabba, Radhika

    2010-01-01

    Caffeine and taurine are two major neuromodulators present in large quantities in many popular energy drinks. We investigated their effects on sleep-wake control in constant darkness using the fruit fly Drosophila as a model system. It has been shown that caffeine, as the most widely used psychostimulant, can boost arousal through the dopamine pathway in the mushroom bodies of flies. Taurine is a GABA receptor agonist, which is inhibitory to neuronal firing. We show here that flies receiving a low dose of caffeine (0.01%) increase locomotor activity by 25%, and decrease total sleep by 15%. Treatment with taurine at 0.1% to 1.5% reduces locomotor activity by 28% to 86%, and shifts it from diurnal to nocturnal. At 0.75%, taurine also increases total sleep by 50%. Our results show that taurine increases sleep, while caffeine, as previously reported, attenuates sleep. Flies treated with both caffeine and taurine exhibit two differential effects which depend upon the ratio of taurine to caffeine. A high taurine:caffeine ratio promotes sleep, while a low ratio of taurine:caffeine inhibits sleep to a greater extent than the equivalent amount of caffeine alone. This intriguing enhancement of caffeine action by low doses of taurine may account for the presence of both compounds in energy-promoting drinks such as Red Bull® and Monster®. PMID:23616711

  20. The role of hepatic transport and metabolism in the interactions between pravastatin or repaglinide and two rOatp inhibitors in rats.

    PubMed

    Badolo, Lassina; Bundgaard, Christoffer; Garmer, Mats; Jensen, Bente

    2013-07-16

    A change in the function or expression of hepatic drug transporters may have significant effect on the efficacy or safety of orally administered drugs. Although a number of clinical drug-drug interactions associated with hepatic transport proteins have been reported, in practice it is not always straightforward to discriminate other pathways (e.g. drug metabolism) from being involved in these interactions. The present study was designed to assess the interactions between organic anion transporting polypeptide (Oatp) substrates (pravastatin or repaglinide) and inhibitors (spironolactone or diphenhydramine) in vivo in rats. The mechanisms behind the interactions were then investigated using in vitro tools (isolated hepatocytes and rat liver microsomes). The results showed a significant increase in the systemic exposures of pravastatin (2.5-fold increase in AUC) and repaglinide (1.8-fold increase in AUC) after co-administration of spironolactone to rats. Diphenhydramine increased the AUC of repaglinide by 1.4-fold. The in vivo interactions observed in rats between Oatp substrates and inhibitors may a priori be classified as transport-mediated drug-drug interactions. However, mechanistic studies performed in vitro using both isolated rat hepatocytes and rat liver microsomes showed that the interaction between pravastatin and spironolactone may be solely linked to the inhibition of pravastatin uptake in liver. On the contrary, the inhibition of cytochrome P450 seemed to be the reason for the interactions observed between repaglinide and spironolactone. Although the function and structure of transport proteins may vary between rats and humans, the approach used in the present study can be applied to humans and help to understand the role of drug transport and drug metabolism in a given drug-drug interaction. This is important to predict and mitigate the risk of drug-drug interactions for a candidate drug in pre-clinical development, it is also important for the optimal

  1. Up-Regulation of the ATP-Binding Cassette Transporter A1 Inhibits Hepatitis C Virus Infection

    PubMed Central

    Gondeau, Claire; Douam, Florian; Lebreton, Stéphanie; Lagaye, Sylvie; Pol, Stanislas; Helle, François; Plengpanich, Wanee; Guérin, Maryse; Bourgine, Maryline; Michel, Marie Louise; Lavillette, Dimitri; Roingeard, Philippe; le Goff, Wilfried; Budkowska, Agata

    2014-01-01

    Hepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes. Furthermore, it generates high-density lipoprotein (HDL) particles. HDL protects against arteriosclerosis and cardiovascular disease. We show that the up-regulation of ABCA1 gene expression and its cholesterol efflux function in Huh7.5 hepatoma cells, using the liver X receptor (LXR) agonist GW3965, impairs HCV infection and decreases levels of virus produced. ABCA1-stimulation inhibited HCV cell entry, acting on virus-host cell fusion, but had no impact on virus attachment, replication, or assembly/secretion. It did not affect infectivity or properties of virus particles produced. Silencing of the ABCA1 gene and reduction of the specific cholesterol efflux function counteracted the inhibitory effect of the GW3965 on HCV infection, providing evidence for a key role of ABCA1 in this process. Impaired virus-cell entry correlated with the reorganisation of cholesterol-rich membrane microdomains (lipid rafts). The inhibitory effect could be reversed by an exogenous cholesterol supply, indicating that restriction of HCV infection was induced by changes of cholesterol content/distribution in membrane regions essential for virus-cell fusion. Stimulation of ABCA1 expression by GW3965 inhibited HCV infection of both human primary hepatocytes and isolated human liver slices. This study reveals that pharmacological stimulation of the ABCA1-dependent cholesterol efflux pathway disrupts membrane cholesterol homeostasis, leading to the

  2. Taurine as a micronutrient in development and regeneration of the central nervous system.

    PubMed

    Lima, L; Obregon, F; Cubillos, S; Fazzino, F; Jaimes, I

    2001-01-01

    Taurine is an amino acid known to possess trophic properties in the central nervous system. The relevance of its presence in maternal milk is related to its role as an essential nutrient. Taurine deficiency around birth produces anatomical and functional modifications in the brain and in the retina. In addition, taurine favors neuron proliferation and survival, as well as neurite extension. The mechanisms by which taurine exerts its trophic role in the regenerating retina are related to increases in calcium fluxes, to modifications of protein phosphorylation, and to influence of the target organ. Moreover, taurine-zinc interaction might be crucial in the development of structures such as the hippocampal formation. Thus, taurine can be considered as one of the determinant nutritional molecules during development and regeneration of the central nervous system.

  3. The effect of insulin on plasma glucose concentrations, expression of hepatic glucose transporters and key gluconeogenic enzymes during the perinatal period in broiler chickens.

    PubMed

    Franssens, Lies; Lesuisse, Jens; Wang, Yufeng; Willems, Els; Willemsen, Hilke; Koppenol, Astrid; Guo, Xiaoquan; Buyse, Johan; Decuypere, Eddy; Everaert, Nadia

    2016-06-01

    Chickens have blood glucose concentrations that are twofold higher than those observed in mammals. Moreover, the insulin sensitivity seems to decrease with postnatal age in both broiler and layer chickens. However, little is known about the response of insulin on plasma glucose concentrations and mRNA abundance of hepatic glucose transporters 1, 2, 3, 8, 9 and 12 (GLUT1, 2, 3, 8, 9 and 12) and three regulatory enzymes of the gluconeogenesis, phosphoenolpyruvate carboxykinase 1 and 2 (PCK1 and 2) or fructose-1,6-biphosphatase 1 (FBP1) in chicks during the perinatal period. In the present study, broiler embryos on embryonic day (ED)16, ED18 or newly-hatched broiler chicks were injected intravenously with bovine insulin (1μg/g body weight (BW)) to examine plasma glucose response and changes in hepatic mRNA abundance of the GLUTs, PCK1 and 2 and FBP1. Results were compared with a non-treated control group and a saline-injected sham group. Plasma glucose levels of insulin-treated ED18 embryos recovered faster from their minimum level than those of insulin-treated ED16 embryos or newly-hatched chicks. In addition, at the minimum plasma glucose level seven hours post-injection (PI), hepatic GLUT2, FBP1 and PCK2 mRNA abundance was decreased in insulin-injected embryos, compared to sham and control groups, being most pronounced when insulin injection occurred on ED16.

  4. Hepatic mobilization of zinc after an experimental surgery, and its relationship with inflammatory cytokines release, and expression of metallothionein and Zip14 transporter.

    PubMed

    Aburto-Luna, Violeta; Treviño, Samuel; Santos-López, Gerardo; Moroni-González, Diana; Calva-Cruz, Oscar; Aguilar-Alonso, Patricia; León-Chávez, Bertha Alicia; Brambila, Eduardo

    2017-02-01

    To study the relationship between the release of inflammatory cytokines and mobilization of zinc into liver, and the expression of metallothionein and Zip14 transporter after an abdominal surgery in rats. Thirty-five male Wistar rats were subjected to experimental surgical stress, then the subgroups of five animals were killed at 3, 6, 9, 12, 16, 20 and 24 h. Matched groups without surgery were used as controls. Zinc levels were determined by AAS, intracellular zinc by zinquin and dithizone staining. Hepatic metallothionein was assayed by a Cd-saturation method, and IL-1β, IL-6, and TNF-β by immunoassays. Zip14 expression was analyzed by real-time RT-PCR, and protein level by immunohistochemistry and Western blot. Experimental surgery produced a hypozincemia, and the increase of hepatic zinc also produced the release of IL-1β, IL-6 in serum, and the increase of hepatic MT. Histochemistry showed a decrease of free zinc at 3-6 h, but an increase at 9 h (zinquin); meanwhile, total intracellular zinc increased after 9 h (dithizone). RNAm and protein levels of Zip14 were elevated between 6 and 20 h after surgery. Biochemical changes described in this work could be part of the APR, and directed to respond to the damage produced during surgical trauma.

  5. Effect of P/S ratio (0. 5 vs 0. 9) on hepatic LDL transport at three levels of dietary cholesterol in cynomolgus macaques

    SciTech Connect

    Hunt, C.E.; Funk, G.M.; Turley, S.D.; Spady, D.K.; Dietschy, J.M. )

    1990-02-26

    Interaction between dietary polyunsaturated to saturated (P/S) fatty acid ratio and cholesterol (C) was studied in 6 groups of male cynomolgus macaques fed diets (oleic acid constant) for 72 weeks as follows (C mg/Cal-P/S): (1), 0.06 - 0.5; (2), 0.06-0.9, (3), 0.28-0.5; (4), 0.28-0.9; (5), 2,35-0.5; (6), 2,35-0.9. Plasma C was proportional to dietary C and was affected significantly by P/S in 1 and 2 only. Mean plasma C (mg/dl) at 72 weeks was: (1) 158; (2) 117; (3) 320; (4) 284; (5) 602; (6) 601. LDL-C was significantly higher in (1) than in (2) (90 vs 65 mg/dl). In vivo LDL turnover studies showed that LDL clearance was suppressed by excess dietary C and by saturated fats in low C diets. Receptor-independent clearance was relatively constant. Hepatic LDL transport was determined after injection of 125I-cellobiose-LDL. Hepatic LDL-C uptake was greater in (2) than in (1). LDL-C synthesis was reduced in (4) and (6) compared to (3) and (5), respectively. The authors conclude that (i) hepatic LDL receptor activity is altered by degree of saturation in dietary triglycerides when dietary C is minimal and (ii) saturated triglycerides enhance LDL-C synthesis when dietary C is ample in this model.

  6. Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.

    PubMed

    Suárez, Luz M; Muñoz, María-Dolores; Martín Del Río, Rafael; Solís, José M

    2016-05-01

    A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age-related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine-dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores.

  7. Echocardiographic evidence for myocardial failure induced by taurine deficiency in domestic cats.

    PubMed Central

    Novotny, M J; Hogan, P M; Flannigan, G

    1994-01-01

    Dietary taurine-deficiency is a cause of dilated cardiomyopathy (DCM) in cats. While the incidence of clinical cases of feline DCM has markedly decreased since the association between DCM and taurine-deficiency was first recognized, not all cats maintained on taurine-deficient diets develop DCM. The objective was to temporally evaluate left ventricular (LV) function using M-mode echocardiography in 23 cats maintained on a taurine-deficient diet; 20 time-matched, taurine-supplemented cats served as controls. The duration of feeding trials ranged from 6-15 months. No diminution of myocardial function was recorded in a small number of taurine-deficient cats whereas cardiac performance in some taurine-deficient cats diminished to levels characteristic of DCM. Of the taurine-deficient cats, 17 (74%) experienced a greater than 25% reduction in fractional shortening and 21 (91%) had a greater than 25% increase in LV end-systolic short-axis diameter. On average, LV end-systolic short-axis diameter increased by 70% and fractional shortening decreased by 37% in taurine-deficient cats. Mean velocity of circumferential fiber shortening was similarly reduced in taurine-deficient cats. The greatest rate of change in M-mode echocardiographic variables occurred during the first four months on the taurine-deficient diet. Dietary taurine deficiency leads to a spectrum of changes in myocardial function in domestic cats. While DCM is observed in some cats, decreased systolic pump function and increased LV end-systolic short-axis diameter are more consistent findings. PMID:8143255

  8. Comparative effect of fish oil feeding and other dietary fatty acids on plasma lipoproteins, biliary lipids, and hepatic expression of proteins involved in reverse cholesterol transport in the rat.

    PubMed

    Morgado, Nora; Rigotti, Attilio; Valenzuela, Alfonso

    2005-01-01

    While elevated plasma high-density lipoprotein (HDL) levels has been associated to a reduction in cardiovascular risk, dietary fish oils rich in omega-3 polyunsaturated fatty acids (PUFAs) may protect against this disease. The protective effect of HDL is associated to its participation in the reverse cholesterol transport pathway. On the other hand, omega-3 PUFAs decrease plasma HDL levels compared to other fatty acids, which may suggest an effect on reverse cholesterol transport. In this work, the effect of dietary fish oil on the fatty acid composition of hepatic membranes, plasma lipoprotein cholesterol profile, biliary lipids, and the expression of proteins involved in reverse cholesterol transport, was compared to other dietary oils having a different degree of fatty acid unsaturation. Male rats were fed a semi synthetic diet containing fish oil (omega-3), sunflower oil (omega-6), olive oil (omega-9) or coconut oil (saturated). Hepatic membrane fatty acid composition, plasma cholesterol levels, lipoprotein cholesterol profile, biliary lipids, hepatic mRNA levels for lecithin cholesterol acyltransferase, hepatic lipase, apo E, and apo A-I, and hepatic protein levels of the scavenger receptor class B type I, caveolin-1, and the ATP binding cassette transporter A1 were analyzed. Plasma apo A-I and apo E protein levels were also evaluated. Compared to the other diets, omega-3 PUFAs significantly changed omega-3/omega-6 fatty acid ratio of hepatic membranes, caused a reduction of plasma total and HDL cholesterol, and selectively increased biliary cholesterol secretion. No modification in the expression levels of lecithin cholesterol acyltransferase, hepatic lipase, apo A-I and apo E mRNA was observed. Hepatic scavenger receptor class B type I, caveolin-1, and the ATP binding cassette transporter A1 protein levels were also not affected. Plasma apo A-I, but not apo E, was reduced. These results show that dietary omega-3 PUFAs reduce plasma HDL cholesterol and

  9. The synthesis and role of taurine in the Japanese eel testis.

    PubMed

    Higuchi, Masato; Celino, Fritzie T; Tamai, Ayako; Miura, Chiemi; Miura, Takeshi

    2012-08-01

    In teleost fish, the progestin 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) is an essential component of the spermatogenesis pathway. In a series of investigations on the mechanisms underlying progestin-stimulated spermatogenesis, we have found that DHP up-regulates the expression of cysteine dioxygenase1 (CDO1) in the Japanese eel testis. CDO1 is one of the enzymes involved in the taurine biosynthesis pathway. To evaluate whether taurine is synthesized in the eel testis, cysteine sulfinate decarboxylase (CSD), another enzyme involved in taurine synthesis, was isolated from this species. RT-PCR and in vitro eel testicular culture revealed that although CSD was also expressed in eel testis, neither DHP nor other sex steroids affect CSD mRNA expression in a similar manner to CDO1. Using an in vitro eel testicular culture system, we further investigated the effects of DHP on taurine synthesis in the eel testis. HPLC analysis showed that DHP treatment significantly increases the taurine levels in the eel testis. These results suggest that DHP promotes taurine synthesis via the up-regulation of CDO1 mRNA expression during eel spermatogenesis. Furthermore, we observed from our analysis that although taurine does not induce complete spermatogenesis, it promotes spermatogonial DNA synthesis and the expression of Spo11, a meiosis-specific marker. These data thus suggest that taurine augments the effects of sex steroids in the promotion of spermatogonial proliferation and/or meiosis and hence that taurine plays important roles in spermatogenesis.

  10. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    PubMed Central

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  11. Partial Agonism of Taurine at Gamma-Containing Native and Recombinant GABAA Receptors

    PubMed Central

    Kletke, Olaf; Gisselmann, Guenter; May, Andrea; Hatt, Hanns; A. Sergeeva, Olga

    2013-01-01

    Taurine is a semi-essential sulfonic acid found at high concentrations in plasma and mammalian tissues which regulates osmolarity, ion channel activity and glucose homeostasis. The structural requirements of GABAA-receptors (GABAAR) gated by taurine are not yet known. We determined taurine potency and efficacy relative to GABA at different types of recombinant GABAAR occurring in central histaminergic neurons of the mouse hypothalamic tuberomamillary nucleus (TMN) which controls arousal. At binary α1/2β1/3 receptors taurine was as efficient as GABA, whereas incorporation of the γ1/2 subunit reduced taurine efficacy to 60–90% of GABA. The mutation γ2F77I, which abolishes zolpidem potentiation, significantly reduced taurine efficacy at recombinant and native receptors compared to the wild type controls. As taurine was a full- or super- agonist at recombinant αxβ1δ-GABAAR, we generated a chimeric γ2 subunit carrying the δ subunit motif around F77 (MTVFLH). At α1/2β1γ2(MTVFLH) receptors taurine became a super-agonist, similar to δ-containing ternary receptors, but remained a partial agonist at β3-containing receptors. In conclusion, using site-directed mutagenesis we found structural determinants of taurine’s partial agonism at γ-containing GABAA receptors. Our study sheds new light on the β1 subunit conferring the widest range of taurine-efficacies modifying GABAAR function under (patho)physiological conditions. PMID:23637894

  12. Isolation and derivatization of plasma taurine for stable isotope analysis by gas chromatography-mass spectrometry

    SciTech Connect

    Irving, C.S.; Klein, P.D.

    1980-09-01

    A method for the isolation and derivatization of plasma taurine is described that allows stable isotope determinations of taurine to be made by gas chromatography-mass spectrometry. The isolation procedure can be applied to 0.1 ml of plasma; the recovery of plasma taurine was 70 to 80%. For gc separation, taurine was converted to its dimethylaminomethylene methyl ester derivative which could not be detected by hydrogen flame ionization, but could be monitored readily by NH/sub 3/ chemical ionization mass spectrometry. The derivatization reaction occurred partially on-column and required optimization of injection conditions. Using stable isotope ratiometry multiple ion detection, (M + 2 + H)/sup +//(M + H)/sup +/ ion ratio of natural abundance taurine was determined with a standard deviation of less than +-0.07% of the ratio. The (1,2-/sup 13/C)taurine/taurine mole ratios of standard mixtures could be accurately determined to 0.001. This stable isotope gc-ms method is suitable for studying the plasma kinetics of (1,2-/sup 13/C)taurine in infants who are at risk with respect to taurine depletion.

  13. Development of a novel cysteine sulfinic Acid decarboxylase knockout mouse: dietary taurine reduces neonatal mortality.

    PubMed

    Park, Eunkyue; Park, Seung Yong; Dobkin, Carl; Schuller-Levis, Georgia

    2014-01-01

    We engineered a CSAD KO mouse to investigate the physiological roles of taurine. The disruption of the CSAD gene was verified by Southern, Northern, and Western blotting. HPLC indicated an 83% decrease of taurine concentration in the plasma of CSAD(-/-). Although CSAD(-/-) generation (G)1 and G2 survived, offspring from G2 CSAD(-/-) had low brain and liver taurine concentrations and most died within 24 hrs of birth. Taurine concentrations in G3 CSAD(-/-) born from G2 CSAD(-/-) treated with taurine in the drinking water were restored and survival rates of G3 CSAD(-/-) increased from 15% to 92%. The mRNA expression of CDO, ADO, and TauT was not different in CSAD(-/-) compared to WT and CSAD mRNA was not expressed in CSAD(-/-). Expression of Gpx 1 and 3 was increased significantly in CSAD(-/-) and restored to normal levels with taurine supplementation. Lactoferrin and the prolactin receptor were significantly decreased in CSAD(-/-). The prolactin receptor was restored with taurine supplementation. These data indicated that CSAD KO is a good model for studying the effects of taurine deficiency and its treatment with taurine supplementation.

  14. Taurine alters respiratory gas exchange and nutrient metabolism in type 2 diabetic rats.

    PubMed

    Harada, Nagakatsu; Ninomiya, Chika; Osako, Yoshie; Morishima, Masaki; Mawatari, Kazuaki; Takahashi, Akira; Nakaya, Yutaka

    2004-07-01

    To assess the effect of taurine supplementation on respiratory gas exchange, which might reflect the improved metabolism of glucose and/or lipid in the type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (16 weeks of age) were randomly divided into two groups: unsupplemented group and taurine-supplemented (3% in drinking water) group. After 9 weeks of treatment, indirect calorimetry and insulin tolerance tests were conducted. The amounts of visceral fat pads, tissue glycogen, the blood concentrations of glucose, triacylglycerol, taurine, and electrolytes, and the level of hematocrit were compared between groups. A nondiabetic rat strain (Long-Evans Tokushima Otsuka) was used as the age-matched normal control. The indirect calorimetry showed that the treatment of OLETF rats with taurine could reduce a part of postprandial glucose oxidation possibly responsible for the increase of triacylglycerol synthesis in the body. Taurine supplementation also improved hyperglycemia and insulin resistance and increased muscle glycogen content in the OLETF rats. Supplementation with taurine increased the blood concentration of taurine and electrolyte and fluid volume, all of which were considered to be related to the improvement of metabolic disturbance in OLETF rats. Taurine supplementation may be an effective treatment for glucose intolerance and fat/lipid accumulation observed in type 2 diabetes associated with obesity. These metabolic changes might be ascribed, in part, to the alteration of circulating blood profiles, where the improved hyperglycemia and/or the blood accumulation of taurine itself would play roles. Copyright 2004 NAASO

  15. Taurine and the control of basal hormone release from rat neurohypophysis.

    PubMed

    Song, Zhilin; Hatton, Glenn I

    2003-10-01

    Pituicytes of pituitary neural lobe are rich in the amino acid taurine, which they release upon hypoosmotic stimulation. As a generally inhibitory amino acid, taurine is thought to activate receptors on neural lobe nerve terminals and exert some control over hormone release. Previous work has shown the presence of glycine and GABA(A) receptors in neural lobe, both of which have affinity for taurine. Using a perifused explant system, we studied the effects of taurine activation of glycine and GABA(A) receptors on basal hormone release. Somewhat surprisingly, taurine induced increases in basal release of both vasopressin and oxytocin. Taurine-induced increases in oxytocin release were blocked by bicuculline, suggesting involvement of GABA(A) receptors. Increases in vasopressin release were not blocked by bicuculline, indicating involvement of receptors other than GABA(A). Although combined bicuculline and strychnine, an antagonist at most glycine receptors, also did not block increased vasopressin release, picrotoxin (a Cl(-) channel blocker) was effective in blocking increases in both vasopressin and oxytocin release. The other receptor(s) involved in taurine actions is postulated to be strychnine-insensitive glycine receptors. Thus, taurine in neural lobe may act via both a GABA(A) receptor and one or more types of glycine receptors to depolarize nerve terminal membranes under basal conditions. Taurine-induced partial depolarization resulting in Na(+) channel inactivation is probably responsible for its previously observed inhibition of stimulated hormone release from neural lobe.

  16. Taurine enhances the sexual response and mating ability in aged male rats.

    PubMed

    Yang, Jiancheng; Lin, Shumei; Feng, Ying; Wu, Gaofeng; Hu, Jianmin

    2013-01-01

    It has been demonstrated that taurine is abundant in male reproductive organs, and can be biosynthesized by testis, but the taurine concentration will reduce with aging. The levels of serum LH, T, NOS, and NO were found to be obviously increased by taurine supplementation in aged rats in our previous study. In addition, aging will result in a significant decline in sexual response and function, which may be attributed to the androgen deficiency. Furthermore, NO has been proposed as a crucial mediator of penile erection. That makes us hypothesize that there is potential relationship between taurine decline and erection dysfunction in aged males. So the primary aim of the present study was to investigate the effect of taurine on male sexuality in rats. Taurine was offered in water to male aged (20 months old) rats for 110 days. The effects of taurine on the sexual response, mating ability, levels of serum reproductive hormones, and penile NOS and NO levels were investigated. The results showed that taurine can significantly reduce the EL and ML; obviously increase the ERF, MF, IF, and EJF; stimulate the secretion of GnRH, LH, and T; and elevate penis NOS and NO level in aged rats. The results indicated that taurine can enhance the sexual response and mating ability in aged male rats by increasing the level of testosterone and NO, but the exact mechanism of which needs to be further investigated.

  17. Effect of taurine on chemoshock seizure thresholds in lead-exposed animals

    SciTech Connect

    Huxtable, R.J.; Shindo, S.; Nakagawa, K.

    1986-03-01

    The high levels of taurine found in developing brain have led to postulates that taurine is involved in brain maturation. The authors have examined the effect of taurine on the chemoshock threshold of rats reared in the presence of the environmental toxin, lead. Within 24 h of giving birth, dams were placed on one of four regimens: Group P received 0.4% lead acetate in the drinking water; Group T received 3% taurine in drinking water; Group PT received both taurine and lead acetate; and Group C received distilled water. The pups were weaned at 21 days, but maintained on the same treatments. Pentylene tetrazole seizure thresholds were determined at 42 days. Thresholds in Group P were significantly depressed relative to Group C (56.0 mg/kg v 79.9 mg/kg). Taurine supplementation had no effect on threshold (T = 72.7 mg/kg). However, thresholds in Group PT were significantly higher than those of Group P (PT = 85.2 mg/kg). These data show that whereas taurine was without effect on the threshold of animals not stressed by exposure to lead, it had a protective effect on exposed animals. As human neonates are unable to synthesize taurine, the findings reinforce the concept of taurine being a conditionally essential nutrient in developing humans.

  18. Effect of caloric restriction and AMPK activation on hepatic nuclear receptor, biotransformation enzyme, and transporter expression in lean and obese mice.

    PubMed

    Kulkarni, Supriya R; Xu, Jialin; Donepudi, Ajay C; Wei, Wei; Slitt, Angela L

    2013-09-01

    Fatty liver alters liver transporter expression. Caloric restriction (CR), the recommended therapy to reverse fatty liver, increases Sirtuin1 deacetylase activity in liver. This study evaluated whether CR and CR mimetics reversed obesity-induced transporter expression in liver and hepatocytes. mRNA and protein expression was determined in adult lean (lean) and leptin-deficient obese (OB) mice fed ad libitum or placed on 40% (kCal) reduced diet. Hepatocytes were isolated from lean and OB mice, treated with AMP Kinase activators, and gene expression was determined. CR decreased Oatp1a1, Oatp1b2, and Abcb11 mRNA expression in lean, but not OB mice. CR increased Abcc2 mRNA OB livers, whereas protein expression increased in both genotypes. CR increased Abcc3 protein expression increased in OB livers. CR did not alter Abcc1, 4 and 5 mRNA expression in lean mice but decreased expression in livers of OB mice. CR increased Abcc4 protein in lean, but not OB mice. CR restriction reversed the expression of some, but not all transporters in livers of OB mice. Overall, these data indicate a potential for CR to restore some hepatic transporter changes in OB mice, but suggest a functional leptin axis is needed for reversal of expression for some transporters.

  19. Conformational Study of Taurine in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Cortijo, Vanessa; Sanz, M. Eugenia; López, Juan C.; Alonso, José L.

    2009-08-01

    The conformational preferences of the amino sulfonic acid taurine (NH2-CH2-CH2-SO3H) have been investigated in the gas phase by laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW) in the 6-14 GHz frequency range. One conformer has been observed, and its rotational, centrifugal distortion, and hyperfine quadrupole coupling constants have been determined from the analysis of its rotational spectrum. Comparison of the experimental constants with those calculated theoretically identifies the detected conformer unambiguously. The observed conformer of taurine is stabilized by an intramolecular hydrogen bond O-H···N between the hydrogen of the sulfonic acid group and the nitrogen atom of the amino group.

  20. Taurine and ellagic acid: two differently-acting natural antioxidants.

    PubMed

    Cozzi, R; Ricordy, R; Bartolini, F; Ramadori, L; Perticone, P; De Salvia, R

    1995-01-01

    Naturally occurring antimutagenic compounds are extensively analyzed for their capacity to protect cells from induced damage. We selected two agents, taurine and ellagic acid, treated in the literature as antioxidants, but whose activity is insufficiently known. This paper reports on the ability of these agents to act against damage induced by mitomycin-C and hydrogen peroxide in Chinese hamster ovary cells cultivated in vitro. Cytogenetic and cytofluorimetric analyses were performed. Ellagic acid proved to have more than one mechanism of action, probably as a scavenger of oxygen species produced by H2O2 treatment, and as a protector of the DNA double helix from alkylating agent injury. In our experimental conditions, taurine seems able to scavenge oxygen species.

  1. High taurine levels in the Solemya velum symbiosis.

    PubMed

    Conway, N M; McDowell Capuzzo, J E

    1992-05-01

    1. To compare biochemical differences between bivalves with and without endosymbiotic chemoautotrophic bacteria, specimens of Solemya velum, a bivalve species known to contain bacterial endosymbionts, and the symbiont-free soft-shelled clam Mya arenaria, were collected from the same subtidal reducing sediments during October and November 1988. 2. Total and free amino acid compositions were determined for both species. Protein-bound amino acids were calculated as the difference between total and free amino acids. In addition, stable isotope ratios of the total and free amino acids of each species were measured to determine potential sources for these molecules. 3. Both species had similar total hydrolyzable- and protein-bound amino acid compositions; approximately 50% of the protein-bound amino acids were essential amino acids. In S. velum, the small size of the digestive system suggests that these amino acids are probably synthesized by the endosymbiotic bacteria and translocated to the animal tissue. The delta 13C and delta 15N ratios of the amino acids are very similar to the isotope ratios previously found in both the endosymbionts and whole tissues of S. velum. The relative and absolute amounts of free amino acids are very different in the two species. In S. velum, the absolute concentrations of taurine, a sulfur-containing amino acid, were greater than the total free amino acid concentrations found in other bivalves. 4. The delta 34S ratios of the free amino acids of S. velum, which were predominantly composed of taurine, were extremely negative (-17.2/1000) suggesting that taurine is synthesized using sulfur originally derived from external reduced sulfur sources, such as pore water sulfides. The possible roles for taurine in this animal-bacteria symbiosis are discussed.

  2. The beneficial effects of taurine to counteract sarcopenia.

    PubMed

    Scicchitano, Bianca M; Sica, Gigliola

    2016-11-22

    Aging is a multifactorial process characterized by several features including low-grade inflammation, increased oxidative stress and reduced regenerative capacity, which ultimately lead to alteration in morpho-functional properties of skeletal muscle, thus promoting sarcopenia. This condition is characterized by a gradual loss of muscle mass due to an unbalance between protein synthesis and degradation, finally conveying in functional decline and disability. The development of specific therapeutic approaches able to block or reverse this condition may represent an invaluable tool for the promotion of a healthy aging among elderly. It is well established that changes in the quantity and the quality of dietary proteins, as well as the intake of specific amino acids, are able to counteract some of the physiopathological processes related to the progression of the loss of muscle mass and may have beneficial effects in improving the anabolic response of muscle in the elderly. Taurine is a non-essential amino acid expressed in high concentration in several mammalian tissues and particularly in skeletal muscle where it is involved in the modulation of intracellular calcium concentration and ion channel regulation and where it also acts as an antioxidant and anti-inflammatory factor. The aim of this review is to summarize the pleiotropic effects of taurine on specific muscle targets and to discuss its role in regulating signaling pathways involved in the maintenance of muscle homeostasis. We also highlight the potential use of taurine as a therapeutic molecule for the amelioration of skeletal muscle function and performance severely compromised during aging.

  3. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  4. Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.

    PubMed

    Hussy, N; Deleuze, C; Pantaloni, A; Desarménien, M G; Moos, F

    1997-08-01

    1. To evaluate the implication of taurine in the physiology of supraoptic neurones, we (i) investigated the agonist properties of taurine on glycine and GABAA receptors of supraoptic magnocellular neurones acutely dissociated from adult rats, using whole-cell voltage clamp, (ii) studied the effects of taurine and strychnine in vivo by extracellular recordings of supraoptic vasopressin neurones in anaesthetized rats, and (iii) measured the osmolarity-dependent release of endogenous taurine from isolated supraoptic nuclei by HPLC. 2. GABA, glycine and taurine evoked rapidly activating currents that all reversed close to the equilibrium potential for Cl-, indicating activation of Cl(-)-selective channels. Glycine-activated currents were reversibly blocked by strychnine (IC50 of 35 nM with 100 microM glycine), but were unaffected by the GABAA antagonist gabazine (1-3 microM). GABA-activated currents were reversibly antagonized by 3 microM gabazine, but not by strychnine (up to 1 microM). 3. Responses to 1 mM taurine were blocked by strychnine but not by gabazine and showed no additivity with glycine-induced currents, indicating selective activation of glycine receptors. Responses to 10 mM taurine were partially antagonized by gabazine, the residual current being blocked by strychnine. Thus, taurine is also a weak agonist of GABAA receptors. 4. In the presence of gabazine, taurine activated glycine receptors with an EC50 of 406 microM. Taurine activated at most 70% of maximal glycine currents, suggesting that it is a partial agonist of glycine receptors. 5. In vivo, locally applied strychnine (300 nM) increased and taurine (1 mM) decreased the basal electrical activity of vasopressin neurones in normally hydrated rats. The effect of strychnine was markedly more pronounced in water-loaded rats. 6. Taurine, which is concentrated in supraoptic glial cells, could be released from isolated supraoptic nuclei upon hyposmotic stimulation. Decreases in osmolarity of 15 and 30

  5. Serum taurine and risk of coronary heart disease: a prospective, nested case-control study

    PubMed Central

    Wójcik, Oktawia P.; Koenig, Karen L.; Zeleniuch-Jacquotte, Anne; Pearte, Camille; Costa, Max; Chen, Yu

    2013-01-01

    Purpose Taurine (2-aminoethanesulfonic acid), a molecule obtained from diet, is involved in bile acid conjugation, blood pressure regulation, anti-oxidation and anti-inflammation. We performed the first prospective study of taurine and CHD risk. Methods We conducted a case-control study nested in the New York University Women’s Health Study to evaluate the association between circulating taurine levels and risk of coronary heart disease (CHD). Taurine was measured in two yearly pre-diagnostic serum samples of 223 CHD cases and 223 matched controls and averaged for a more reliable measurement of long-term taurine levels. Results Mean serum taurine was positively related to age and dietary intake of poultry, niacin, vitamin B1, fiber, and iron, and negatively related to dietary intake of saturated fat (all p values ≤ 0.05). There was no statistically significant association between the risk of CHD and serum taurine levels. The adjusted ORs for CHD in increasing taurine tertiles were 1.0 (reference), 0.85 (95% CI, 0.51–1.40), and 0.66 (0.39–1.13; p for trend = 0.14). There was a significant inverse association between serum taurine and CHD risk among women with high total serum cholesterol (>250 mg/dl) (adjusted OR = 0.39 (0.19–0.83) for the third vs. first tertile; p for trend = 0.02) but not among those with low total serum cholesterol (p for interaction = 0.01). The data suggest a possible inverse association of serum taurine with diabetes and hypertension risk. Conclusions The findings suggest that high levels of taurine may be protective against CHD among individuals with high serum cholesterol levels. PMID:22322924

  6. Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure

    PubMed Central

    2014-01-01

    Background Excessive manganese exposure induced cognitive deficit. Several lines of evidence have demonstrated that taurine improves cognitive impairment induced by numerous neurotoxins. However, the role of taurine on manganese-induced damages in learning and memory is still elusive. This goal of this study was to investigate the beneficial effect of taurine on learning and memory capacity impairment by manganese exposure in an animal model. Results The escape latency in the Morris Water Maze test was significantly longer in the rats injected with manganese than that in the rats received both taurine and manganese. Similarly, the probe trial showed that the annulus crossings were significantly greater in the taurine plus manganese treated rats than those in the manganese-treated rats. However, the blood level of manganese was not altered by the taurine treatment. Interestingly, the exposure of manganese led to a significant increase in the acetylcholinesterase activity and an evidently decrease in the choline acetyltransferase activity, which were partially restored by the addition of taurine. Additionally, we identified 9 differentially expressed proteins between the rat hippocampus treated by manganese and the control or the manganese plus taurine in the proteomic analysis using the 2-dimensional gel electrophoresis followed by the tandem mass spectrometry (MS/MS). Most of these proteins play a role in energy metabolism, oxidative stress, inflammation, and neuron synapse. Conclusions In summary, taurine restores the activity of AChE and ChAT, which are critical for the regulation of acetylcholine. We have identified seven differentially expressed proteins specifically induced by manganese and two proteins induced by taurine from the rat hippocampus. Our results support that taurine improves the impaired learning and memory ability caused by excessive exposure of manganese. PMID:24885898

  7. Serum taurine and risk of coronary heart disease: a prospective, nested case-control study.

    PubMed

    Wójcik, Oktawia P; Koenig, Karen L; Zeleniuch-Jacquotte, Anne; Pearte, Camille; Costa, Max; Chen, Yu

    2013-02-01

    Taurine (2-aminoethanesulfonic acid), a molecule obtained from diet, is involved in bile acid conjugation, blood pressure regulation, anti-oxidation and anti-inflammation. We performed the first prospective study of taurine and CHD risk. We conducted a case-control study nested in the New York University Women's Health Study to evaluate the association between circulating taurine levels and risk of coronary heart disease (CHD). Taurine was measured in two yearly pre-diagnostic serum samples of 223 CHD cases and 223 matched controls and averaged for a more reliable measurement of long-term taurine levels. Mean serum taurine was positively related to age and dietary intake of poultry, niacin, vitamin B1, fiber and iron, and negatively related to dietary intake of saturated fat (all p values ≤ 0.05). There was no statistically significant association between serum taurine levels and the risk of CHD in the overall study population. The adjusted ORs for CHD in increasing taurine tertiles were 1.0 (reference), 0.85 (95% CI, 0.51-1.40) and 0.66 (0.39-1.13; p for trend = 0.14). There was a significant inverse association between serum taurine and CHD risk among women with high total serum cholesterol (>250 mg/dL) (adjusted OR = 0.39 (0.19-0.83) for the third versus first tertile; p for trend = 0.02) but not among those with low total serum cholesterol (p for interaction = 0.01). The data suggest a possible inverse association of serum taurine with diabetes and hypertension risk. The findings suggest that high levels of taurine may be protective against CHD among individuals with high serum cholesterol levels.

  8. Taurine protects cardiac contractility in killifish, Fundulus heteroclitus, by enhancing sarcoplasmic reticular Ca(2+) cycling.

    PubMed

    Henry, Elenor F; MacCormack, Tyson J

    2017-05-23

    Intracellular taurine is abundant in many animals and it influences an array of physiological processes, including osmoregulation, metabolism, and cardiac contractility. Taurine is an important osmolyte in teleost hearts, but its role in stress tolerance, cardiac metabolism, and contractility has not been assessed. The goal of this study was to determine if ventricular taurine concentration changes in response to environmental stress and to characterize its influence on contractility. Cardiac taurine concentrations varied in killifish (Fundulus heteroclitus) but were generally maintained following acute environmental challenges. In isometrically contracting ventricular strips, supplemental taurine (40 mmol L(-1)) protected peak tension development (F max) at high stimulation frequencies, an effect abolished by treatment with ryanodine, a blocker of sarcoplasmic reticulum Ca(2+) release. In the presence of ryanodine, taurine-treated preparations were also better able to maintain F max at supraphysiological extracellular Ca(2+) levels, but a prior anoxia exposure abolished this effect. Taurine had no impact on basal F max during or after anoxia, but it provided additive protection to high-frequency contractility post-anoxia. Tissue oxygen consumption and extracellular glucose utilization were unaffected by taurine in non-contracting preparations, indicating that it does not impact energy metabolism. Overall, the results suggest that cardiac taurine levels are well maintained on acute time scales in this highly stress-tolerant species. Supplemental taurine has no effect on aerobic metabolism in vitro, but it significantly improved cardiac contractility in a manner dependent upon sarcoplasmic reticulum Ca(2+) cycling. The data indicate that taurine likely plays an important role in the regulation of cardiac performance in teleosts.

  9. Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure.

    PubMed

    Lu, Cai-Ling; Tang, Shen; Meng, Zhi-Juan; He, Yi-Yuan; Song, Ling-Yong; Liu, Yin-Pin; Ma, Ning; Li, Xi-Yi; Guo, Song-Chao

    2014-05-24

    Excessive manganese exposure induced cognitive deficit. Several lines of evidence have demonstrated that taurine improves cognitive impairment induced by numerous neurotoxins. However, the role of taurine on manganese-induced damages in learning and memory is still elusive. This goal of this study was to investigate the beneficial effect of taurine on learning and memory capacity impairment by manganese exposure in an animal model. The escape latency in the Morris Water Maze test was significantly longer in the rats injected with manganese than that in the rats received both taurine and manganese. Similarly, the probe trial showed that the annulus crossings were significantly greater in the taurine plus manganese treated rats than those in the manganese-treated rats. However, the blood level of manganese was not altered by the taurine treatment. Interestingly, the exposure of manganese led to a significant increase in the acetylcholinesterase activity and an evidently decrease in the choline acetyltransferase activity, which were partially restored by the addition of taurine. Additionally, we identified 9 differentially expressed proteins between the rat hippocampus treated by manganese and the control or the manganese plus taurine in the proteomic analysis using the 2-dimensional gel electrophoresis followed by the tandem mass spectrometry (MS/MS). Most of these proteins play a role in energy metabolism, oxidative stress, inflammation, and neuron synapse. In summary, taurine restores the activity of AChE and ChAT, which are critical for the regulation of acetylcholine. We have identified seven differentially expressed proteins specifically induced by manganese and two proteins induced by taurine from the rat hippocampus. Our results support that taurine improves the impaired learning and memory ability caused by excessive exposure of manganese.

  10. Effect of dietary taurine supplementation on growth, feed efficiency, and nutrient composition of juvenile sablefish (Anoplopoma fimbria)

    USDA-ARS?s Scientific Manuscript database

    Juvenile sablefish were fed a low taurine, basal feed with seven graded levels of supplemental taurine to determine taurine requirements for growth and feed efficiency. The basal feed was plant based, formulated primarily with soy and corn proteins with a minimal (9%) amount of fishmeal. The unsuppl...

  11. [Measurement of C14 beta-radioactivity of stable natural origin taurine (2-aminoethanesulfonic acid) in bovine bile].

    PubMed

    Gaetano, G; Bisegna, F; Bisio, V; Parenti, M

    1994-01-01

    Taurine from natural sources has gained great importance as essential nutrient in milk for formula-fed infants. There is a strong request for a method capable of determining the natural origin of taurine. The measure of beta-radioactivity of 14C of taurine by means of liquid scintillation counting proved the most reliable. A simple method is reported.

  12. Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Clearance and Liver Partitioning of OATP and OCT Substrates in Cynomolgus Monkeys.

    PubMed

    Morse, Bridget L; MacGuire, Jamus G; Marino, Anthony M; Zhao, Yue; Fox, Maxine; Zhang, Yueping; Shen, Hong; Griffith Humphreys, W; Marathe, Punit; Lai, Yurong

    2017-10-10

    In the present investigations, we evaluate in vitro hepatocyte uptake and partitioning for the prediction of in vivo clearance and liver partitioning. Monkeys were intravenously co-dosed with rosuvastatin and bosentan, substrates of the organic anion transporting polypeptides (OATPs), and metformin, a substrate of organic cation transporter 1 (OCT1). Serial plasma and liver samples were collected over time. Liver and plasma unbound fraction was determined using equilibrium dialysis. In vivo unbound partitioning (Kpu,u) for rosuvastatin, bosentan, and metformin, calculated from total concentrations in the liver and plasma, were 243, 553, and 15, respectively. A physiologically based pharmacokinetic monkey model that incorporates active and passive hepatic uptake was developed to fit plasma and liver concentrations. In addition, a two-compartment model was used to fit in vitro hepatic uptake curves in suspended monkey hepatocyte to determine active uptake, passive diffusion, and intracellular unbound fraction parameters. At steady-state in the model, in vitro Kpu,u was determined. The results demonstrated that in vitro values under-predicted in vivo active uptake for rosuvastatin, bosentan, and metformin by 6.7-, 28-, and 1.5-fold, respectively, while passive diffusion was over-predicted. In vivo Kpu,u values were under-predicted from in vitro data by 30-, 79-, and 3-fold. In conclusion, active uptake and liver partitioning in monkeys for OATP substrates were greatly under-predicted from in vitro hepatocyte uptake, while OCT-mediated uptake and partitioning scaled reasonably well from in vitro, demonstrating substrate- and transporter-dependent scaling factors. The combination of in vitro experimental and modeling approaches proved useful for assessing prediction of in vivo intracellular partitioning.

  13. Ultraviolet A induces transport of compatible organic osmolytes in human dermal fibroblasts.

    PubMed

    Warskulat, Ulrich; Brookmann, Stefanie; Felsner, Ingo; Brenden, Heidi; Grether-Beck, Susanne; Häussinger, Dieter

    2008-12-01

    Compatible organic osmolytes, such as betaine, myo-inositol and taurine, are involved in cell protection. Human dermal fibroblasts accumulate these osmolytes and express mRNA specific for their transporting systems betaine-/gamma-amino-n-butyric acid (GABA) transporter (BGT-1), sodium-dependent myo-inositol transporter (SMIT) and taurine transporter (TAUT). Taurine uptake was about sixfold higher than that of betaine and myo-inositol. Compared with normoosmotic (305 mOsm/l) control, hyperosmotic exposure (405 mOsm/l) led to a twofold induction of osmolyte uptake. Ultraviolet A (UVA) upregulated osmolyte transporter mRNA levels and increased osmolyte uptake. Taurine inhibited UVA-induced interleukin-6 (Il-6) mRNA expression by 40%. Furthermore, Il-6 accumulation in the supernatants of UVA-irradiated dermal fibroblasts was much slower when cells were preincubated with taurine. These data indicate that taurine accumulation seems to be part of the fibroblast response to UVA radiation and may protect against UVA-induced Il-6 overexpression.

  14. Effect of hepatitis C virus infection on the mRNA expression of drug transporters and cytochrome p450 enzymes in chimeric mice with humanized liver.

    PubMed

    Kikuchi, Ryota; McCown, Matthew; Olson, Pamela; Tateno, Chise; Morikawa, Yoshio; Katoh, Yumiko; Bourdet, David L; Monshouwer, Mario; Fretland, Adrian J

    2010-11-01

    The expression of drug transporters and metabolizing enzymes is a primary determinant of drug disposition. Chimeric mice with humanized liver, including PXB mice, are an available model that is permissive to the in vivo infection of hepatitis C virus (HCV), thus being a promising tool for investigational studies in development of new antiviral molecules. To investigate the potential of HCV infection to alter the pharmacokinetics of small molecule antiviral therapeutic agents in PXB mice, we have comprehensively determined the mRNA expression profiles of human ATP-binding cassette (ABC) transporters, solute carrier (SLC) transporters, and cytochrome P450 (P450) enzymes in the livers of these mice under noninfected and HCV-infected conditions. Infection of PXB mice with HCV resulted in an increase in the mRNA expression levels of a series of interferon-stimulated genes in the liver. For the majority of genes involved in drug disposition, minor differences in the mRNA expression of ABC and SLC transporters as well as P450s between the noninfected and HCV-infected groups were observed. The exceptions were statistically significantly higher expression of multidrug resistance-associated protein 4 and organic anion-transporting polypeptide 2B1 and lower expression of organic cation transporter 1 and CYP2D6 in HCV-infected mice. Furthermore, the enzymatic activities of the major human P450s were, in general, comparable in the two experimental groups. These data suggest that the pharmacokinetic properties of small molecule antiviral therapies in HCV-infected PXB mice are likely to be similar to those in noninfected PXB mice. However, caution is needed in the translation of this relationship to HCV-infected patients as the PXB mouse model does not accurately reflect the pathology of patients with chronic HCV infection.

  15. Taurine depresses cardiac contractility and enhances systemic heart glucose utilization in the cuttlefish, Sepia officinalis.

    PubMed

    MacCormack, Tyson J; Callaghan, N I; Sykes, A V; Driedzic, W R

    2016-02-01

    Taurine is the most abundant amino acid in the blood of the cuttlefish, Sepia officinalis, where levels can exceed 200 mmol L(-1). In mammals, intracellular taurine modulates cardiac Ca(2+) handling and carbohydrate metabolism at much lower concentrations but it is not clear if it exerts similar actions in cephalopods. Blood Ca(2+) levels are high in cephalopods and we hypothesized that taurine would depress cardiac Ca(2+) flux and modulate contractility in systemic and branchial hearts of cuttlefish. Heart performance was assessed with an in situ perfused systemic heart preparation and contractility was evaluated using isometrically contracting systemic and branchial heart muscle rings. Stroke volume, cardiac output, and Ca(2+) sensitivity were significantly lower in systemic hearts perfused with supplemental taurine (100 mmol L(-1)) than in controls. In muscle ring preparations, taurine impaired relaxation at high contraction frequencies, an effect abolished by supra-physiological Ca(2+) levels. Taurine did not affect oxygen consumption in non-contracting systemic heart muscle, but extracellular glucose utilization was twice that of control preparations. Collectively, our results suggest that extracellular taurine depresses cardiac Ca(2+) flux and potentiates glucose utilization in cuttlefish. Variations in taurine levels may represent an important mechanism for regulating cardiovascular function and metabolism in cephalopods.

  16. Specific role of taurine in the 8-brominated-2'-deoxyguanosine formation.

    PubMed

    Asahi, Takashi; Nakamura, Yoshimasa; Kato, Yoji; Osawa, Toshihiko

    2015-11-15

    At the sites of inflammation, hypohalous acids, such as hypochlorous acid and hypobromous acid (HOBr), are produced by myeloperoxidase. These hypohalous acids rapidly react with the primary amino groups to produce haloamines, which are relatively stable and can diffuse long distances and cross the plasma membrane. In this study, we examined the effects of taurine, the most abundant free amino acid in the leukocyte cytosol, on the hypohalous acid-dependent formation of 8-chloro-2'-deoxyguanosine (8-CldG) and 8-bromo-2'-deoxyguanosine (8-BrdG). The reaction of taurine with HOBr yielded taurine bromamine, which is the most stable among other bromamines of amino acids. Taurine also enhanced the bromination of only dG among the four 2'-deoxynucleosides, whereas it inhibited the 8-CldG formation. The specificity of taurine for the enhanced formation of halogenated dG is completely different from that of nicotine, an enhancer of chlorination. The amount of dibrominated taurine (taurine dibromamine) closely correlated with the formation of 8-BrdG, suggesting that taurine dibromamine might be a plausible mediator for the dG bromination in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Taurine activates delayed rectifier KV channels via a metabotropic pathway in retinal neurons

    PubMed Central

    Bulley, Simon; Liu, Yufei; Ripps, Harris; Shen, Wen

    2013-01-01

    Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (KV) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl− channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT2A receptor antagonist, MDL11939. Moreover, we found that taurine enhanced KV channels via intracellular protein kinase C-mediated pathways. When 5-HT2A receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT2 receptor activator, produced a similar regulation of KIR channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT2A receptors and related intracellular pathways. PMID:23045337

  18. Assessment of taurine bioavailability in pelleted and extruded diets with red drum Sciaenops ocellatus

    USDA-ARS?s Scientific Manuscript database

    Taurine has been reported to be efficacious in supporting growth of carnivorous fish species, particularly when supplemented to diets primarily containing plant feedstuffs. Although taurine may become unavailable to some extent by heat and moisture, and is susceptible to the Maillard reaction with r...

  19. Protective and therapeutic effectiveness of taurine in diabetes mellitus: a rationale for antioxidant supplementation.

    PubMed

    Sirdah, Mahmoud M

    2015-01-01

    Taurine, 2-amino ethanesulfonic acid, is a conditionally essential β amino acid which is not utilized in protein synthesis. Taurine is one of the most abundant free amino acids in mammals tissues and is one of the three well-known sulfur-containing amino acids; the others are methionine and cysteine which are considered as the precursors for taurine synthesis. Different scientific studies emphasize on the cytoprotective properties of taurine which included antioxidation, antiapoptosis, membrane stabilization, osmoregulation, and neurotransmission. Protective and therapeutic ameliorations of oxidative stress-induced pathologies were also attributed to taurine both in experimental and human models. Data demonstrating the beneficial effectiveness of taurine against type 1 and type 2 diabetes mellitus and their complications are growing and providing a better understanding of the underlying molecular mechanisms. Although the clinical studies are limited compared to the experimental ones, the present updated systematic review of the literature is set up to provide experimental and clinical evidences regarding the effectiveness of taurine in the context of diabetes mellitus and its complications. Gathering these scientific effects of taurine on diabetes mellitus could provide the physicians and specially the endocrinologists with a comprehensive overview on possible trends in the prevention and management of the disease and its complications through antioxidant supplementation. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  20. Plasma taurine levels are not affected by vigabatrin in pediatric patients.

    PubMed

    Spelbrink, Emily M; Mabud, Tarub S; Reimer, Richard; Porter, Brenda E

    2016-08-01

    Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  1. Use of taurine additives in enhanced oil recovery with anionic surfactants

    SciTech Connect

    Prukop, G.; Chea, C.K.

    1990-12-11

    This patent describes a method disclosed for increasing the recovery of oil in enhanced oil recovery operations employing anionic surfactant by blending a taurine with the anionic surfactant. The taurine may also increase the salt and divalent ion tolerance of the aniomic surfactant.

  2. The physiological and pathophysiological roles of taurine in adipose tissue in relation to obesity.

    PubMed

    Murakami, Shigeru

    2017-10-01

    Obesity is caused by an imbalance between energy intake and energy expenditure. It is established that obesity is a state of low-grade chronic inflammation, which is characterized by enlarged hypertrophied adipocytes, increased infiltration by macrophages and marked changes in the secretion of adipokines and free fatty acids. The effects of taurine on the pathogenesis of obesity have been reported in animals and humans. Although the mechanisms underlying the anti-obesity action of taurine remain to be defined, taurine seems to ameliorate obesity through stimulation of energy expenditure, modulation of lipid metabolism, anorexic effect, anti-inflammatory and anti-oxidative effects. Recent studies revealed that taurine supplementation reduces the infiltration of macrophages and modulates the polarization of adipose tissue macrophages in high-fat diet-induced obese mice. In addition, taurine downregulates the production of pro-inflammatory cytokines by adipocytes, suggesting that taurine plays an anti-inflammatory role in adipose tissue. This article reviews the effects and mechanisms of taurine on the development of obesity, focusing on the role of taurine in white adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Taurine supplementation in spontaneously hypertensive rats: Advantages and limitations for human applications.

    PubMed

    Suwanich, Atchariya; Wyss, J Michael; Roysommuti, Sanya

    2013-11-26

    Taurine (2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions.

  4. Inhibitory Effect of Taurine on Biofilm Formation During Alkane Degradation in Acinetobacter oleivorans DR1.

    PubMed

    Eom, Hyo Jung; Park, Woojun

    2017-06-15

    Taurine, 2-aminoethanesulfonate, is known to function as an antioxidant or membrane stabilizer in eukaryotic cells, but its role in bacteria has been poorly characterized. Biofilm formation of Acinetobacter oleivorans DR1 was significantly reduced by taurine only during alkane degradation, suggesting that taurine affects alkane-induced cell surface. Structurally similar compounds harboring an amine group such as hypotaurine or ethylenediamine have a similar effect, which was not observed with sulfonate-containing chemicals such as ethanesulfonic acid, hexanesulfonic acid. Our biochemical assays and physiological tests demonstrate that taurine reduced cell surface hydrophobicity, which resulted in interruption of the interactions between cells and oily substrate surfaces, such that cells utilized alkanes less effectively. Interestingly, taurine-mediated reduction of quorum sensing (QS) signal production and QS-control sapA gene expression indicated that membrane permeability of quorum signals was also interfered by taurine. Composition and biomass of extracellular polymeric saccharides were changed in taurine-amended conditions. Taken together, our data provide evidence that amine-containing taurine can inhibit biofilm formation of DR1 cells during alkane degradation by (i) changing cell surface charge and (ii) reducing membrane hydrophobicity and QS sensing.

  5. Taurine-induced modulation of voltage-sensitive Na+ channels in rat dorsal root ganglion neurons.

    PubMed

    Yu, Shan-Shan; Yu, Kuai; Gu, Yan; Ruan, Di-Yun

    2005-08-15

    The physiological role of taurine, an abundant free amino acid in the neural system, is still poorly understood. The aim of this study was to investigate its effect on TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents in enzymatically dissociated neurons from rat dorsal root ganglion (DRG) with conventional whole-cell recording manner under voltage-clamp conditions. A TTX-S Na+ current was recorded preferentially from large DRG neurons and a TTX-R Na+ current preferentially from small ones. For TTX-S Na+ channel, taurine of the concentration > or = 10 mM shifted the activation curve in the depolarizing direction and the inactivation curve in the hyperpolarizing direction. There was no change in the activation curve for TTX-R Na+ channel and the inactivation curve was shifted in the hyperpolarizing direction slightly in the presence of taurine > or = 20 mM. When the recovery kinetics was examined, the presence of taurine resulted in a slower recovery from inactivation of TTX-S currents and no change of TTX-R ones. All the effects of taurine were weakly concentration-dependent and partly recovered quite slowly after washout. Our data indicate that taurine alters the properties of Na+ currents in intact DRG neurons. These may contribute to the understanding of taurine as a natural neuroprotectant and the potential of taurine as a useful medicine for the treatment of sensory neuropathies.

  6. Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth performance

    USDA-ARS?s Scientific Manuscript database

    Taurine is a beta-amino sulfur amino acid found in most animal tissues that has many important biological functions including bile salt conjugation, cellular osmoregulation, neuromodulation, calcium signaling. The benefits of supplementing diets with taurine are just beginning to be realized in a n...

  7. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    SciTech Connect

    Huang, J.-S. Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-12-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27{sup Kip1}, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells.

  8. Taurine Treatment Modulates Circadian Rhythms in Mice Fed A High Fat Diet.

    PubMed

    Figueroa, Ana Lucia C; Figueiredo, Hugo; Rebuffat, Sandra A; Vieira, Elaine; Gomis, Ramon

    2016-11-18

    Close ties have been made among certain nutrients, obesity, type 2 diabetes and circadian clocks. Among nutrients, taurine has been documented as being effective against obesity and type 2 diabetes. However, the impact of taurine on circadian clocks has not been elucidated. We investigated whether taurine can modulate or correct disturbances in daily rhythms caused by a high-fat diet in mice. Male C57BL/6 mice were divided in four groups: control (C), control + taurine (C+T), high-fat diet (HFD) and HFD + taurine (HFD+T). They were administered 2% taurine in their drinking water for 10 weeks. Mice were euthanized at 6:00, 12:00, 18:00, and 24:00. HFD mice increased body weight, visceral fat and food intake, as well as higher levels of glucose, insulin and leptin, throughout the 24 h. Taurine prevented increments in food intake, body weight and visceral fat, improved glucose tolerance and insulin sensitivity and reduced disturbances in the 24 h patterns of plasma insulin and leptin. HFD downregulated the expression of clock genes Rev-erbα, Bmal1, and Per1 in pancreatic islets. Taurine normalized the gene and protein expression of PER1 in beta-cells, which suggests that it could be beneficial for the correction of daily rhythms and the amelioration of obesity and diabetes.

  9. Taurine Treatment Modulates Circadian Rhythms in Mice Fed A High Fat Diet

    PubMed Central

    Figueroa, Ana Lucia C.; Figueiredo, Hugo; Rebuffat, Sandra A.; Vieira, Elaine; Gomis, Ramon

    2016-01-01

    Close ties have been made among certain nutrients, obesity, type 2 diabetes and circadian clocks. Among nutrients, taurine has been documented as being effective against obesity and type 2 diabetes. However, the impact of taurine on circadian clocks has not been elucidated. We investigated whether taurine can modulate or correct disturbances in daily rhythms caused by a high-fat diet in mice. Male C57BL/6 mice were divided in four groups: control (C), control + taurine (C+T), high-fat diet (HFD) and HFD + taurine (HFD+T). They were administered 2% taurine in their drinking water for 10 weeks. Mice were euthanized at 6:00, 12:00, 18:00, and 24:00. HFD mice increased body weight, visceral fat and food intake, as well as higher levels of glucose, insulin and leptin, throughout the 24 h. Taurine prevented increments in food intake, body weight and visceral fat, improved glucose tolerance and insulin sensitivity and reduced disturbances in the 24 h patterns of plasma insulin and leptin. HFD downregulated the expression of clock genes Rev-erbα, Bmal1, and Per1 in pancreatic islets. Taurine normalized the gene and protein expression of PER1 in beta-cells, which suggests that it could be beneficial for the correction of daily rhythms and the amelioration of obesity and diabetes. PMID:27857215

  10. Comparison of mercury sulfides with mercury chloride and methylmercury on hepatic P450, phase-2 and transporter gene expression in mice.

    PubMed

    Xu, S F; Wu, Q; Zhang, B B; Li, H; Xu, Y S; Du, Y Z; Wei, L X; Liu, J

    2016-09-01

    Zuotai (mainly β-HgS) and Zhusha (also called as cinnabar, mainly α-HgS) are used in traditional medicines in combination with herbs or even drugs in the treatment of various disorders, while mercury chloride (HgCl2) and methylmercury (MeHg) do not have known medical values but are highly toxic. This study aimed to compare the effects of mercury sulfides with HgCl2 and MeHg on hepatic drug processing gene expression. Mice were orally administrated with Zuotai (β-HgS, 30mg/kg), α-HgS (HgS, 30mg/kg), HgCl2 (33.6mg/kg), or MeHg (3.1mg/kg) for 7days, and the expression of genes related to phase-1 drug metabolism (P4