Abstract: Taurine, a sulphur containing amino acid, is the most abundant intracellular amino acid in humans, and is implicated in numerous biological and physiological functions. This comprehensive overview explores areas, from its characterisation to its potential clinical benefit as a conditionally essential amino acid and a pharmaconutrient. In healthy individuals the diet is the usual source of taurine; although in the presence of vitamin B6 it is also synthesised from methionine and cysteine. Taurine has a unique chemical structure that implies important physiological functions: bile acid conjugation and cholestasis prevention, antiarrhythmic/inotropic/chronotropic effects, central nervous system neuromodulation, retinal development and function, endocrine/metabolic effects and antioxidant/antiinflammatory properties. Taurine is an essential amino acid for preterm neonates and is assured by breast milk. Specific groups of individuals are at risk for taurine deficiency and may benefit from supplementation, e.g. patients requiring long-term parenteral nutrition (including premature and newborn infants); those with chronic hepatic, heart or renal failure. Further studies are required to determine the benefits of replenishing taurine pools as well as the need to include taurine routinely in parenteral nutrition regimens.

Abstract: SPECIFIC AIMSIn view of the immunomodulatory and cytoprotective effects of taurine, a mouse model with a disrupted gene coding for the Na+-dependent taurine transporter (taut−/− mice) was generated: besides reduced fertility and markedly decreased taurine levels in a variety of tissues, these mice show a loss of vision due to severe retinal degeneration resembling human retinitis pigmentosa. The study identifies an important role of the taurine transporter (TAUT) for the development and maintenance of retinal function and morphology.PRINCIPAL FINDINGS1) TAUT knockout mice (taut−/− mice) exhibit reduced fertilityAn 18 kb genomic clone was isolated from a λ phage library containing mouse strain 129SvJ genomic DNA by screening with a cDNA taut probe. To disrupt the taut locus, an isogenic targeting vector was designed to delete exon 1 of taut. Embryonic stem (ES) cells were electroporated with the linearized vector and two ES clones containing the targeting event were injected into blastocysts of C57BL/6 mic...

Abstract: The effects of taurine in the mammalian nervous system are numerous and varied There has been great difficulty in determining the specific targets of taurine action The authors present a review of accepted taurine action and highlight recent discoveries regarding taurine and calcium homeostasis in neurons In general there is a consensus that taurine is a powerful agent in regulating and reducing the intracellular calcium levels in neurons After prolonged L-glutamate stimulation, neurons lose the ability to effectively regulate intracellular calcium This condition can lead to acute swelling and lysis of the cell, or culminate in apoptosis Under these conditions, significant amounts of taurine (mM range) are released from the excited neuron This extracellular taurine acts to slow the influx of calcium into the cytosol through both transmembrane ion transporters and intracellular storage pools Two specific targets of taurine action are discussed: Na+-Ca2+ exchangers, and metabotropic receptors mediating phospholipase-C

Abstract: Previous studies have shown that iron deficiency (ID) increases brain manganese (Mn), but specific regional changes have not been addressed. Weanling rats were fed one of three semipurified diets: control (CN), iron deficient (ID), or iron deficient/manganese fortified (IDMn+). Seven brain regions were analyzed for Mn concentration and amino acid (glutamate, glutamine, taurine, γ-aminobutyric acid) concentrations. Both ID and IDMn+ diets caused significant (p<0.05) increases in Mn concentration across brain regions compared to CN. The hippocampus was the only brain region in which the IDMn+ group accumulated significantly more Mn than both the CN and ID groups. ID significantly decreased GABA concentration in hippocampus, caudate putamen, and globus pallidus compared to CN rats. Taurine was significantly increased in the substantia nigra of the IDMn+ group compared to both ID and CN. ID also altered glutamate and glutamine concentrations in cortex, caudate putamen, and thalamus compared to CN. In the substantia nigra, Mn concentration positively correlated with increased taurine concentration, whereas in caudate putamen, Mn concentration negatively correlated with decreased GABA. These data show that ID is a significant risk factor for central nervous system Mn accumulation and that some of the neurochemical alterations associated with ID are specifically attributable to Mn accumulation.

Abstract: In vivo microdialysis was used to investigate whether nitric oxide (NO) modulates striatal neurotransmitter release in the rat through inducing cyclic GMP formation via soluble guanylate cyclase or formation of peroxynitrite (ONOO(-)). When NO donors, S-nitroso-N-acetyl-DL-penicillamine (SNAP; 1 mM) or (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1, 2-diolate (NOC-18; 1 mM), were retrodialysed for 15 min, acetylcholine (ACh), serotonin (5-HT), glutamate (Glu), gamma-aminobutyric acid (GABA), and taurine levels were significantly increased, whereas those of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were decreased. Only effects on ACh, 5-HT, and GABA showed calcium dependency. Inhibition of soluble guanylate cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ; 100 and 200 microM) dose-dependently reduced NO donor-evoked increases in ACh, 5-HT, Glu, and GABA levels. Coperfusion of SNAP or NOC-18 with an ONOO(-) scavenger, L-cysteine (10 mM) resulted in enhanced concentrations of Glu and GABA. On the other hand, DA concentrations increased rather than decreased, and no reductions in DOPAC and 5-HIAA occurred. This increase in DA and the potentiation of Glu and GABA were calcium-dependent and prevented by ODQ. Similar to NO, infusions of ONOO(-) (10 or 100 microM) decreased DA, DOPAC, and 5-HIAA. Overall, these results demonstrate that NO increases ACh, 5-HT, Glu, and GABA levels primarily through a cyclic GMP-dependent mechanism. For DA, DOPAC, and 5-HIAA, effects are determined by levels of ONOO(-) stimulated by NO donors. When these are high, they effectively reduce extracellular concentrations through oxidation. When they are low, DA concentrations are increased in a cyclic GMP-dependent manner and may act to facilitate Glu and GABA release further. Thus, changes in brain levels of antioxidants, and the altered ability of NO to stimulate cyclic GMP formation during ageing, or neurodegenerative pathologies, may particularly impact on the functional consequences of NO on striatal dopaminergic and glutamatergic function.

Abstract: Oral taurine treatment has been studied extensively as a hypotensive agent. Several rat models of hypertension have been used to prove that dietary taurine supplementation can alleviate high blood pressure, among other cardiovascular problems. Experimental models mentioned in this review are the spontaneously hypertensive rat, the DOCA-salt rat, the Dahl-S rat, the renovascular hypertensive rat, the hyperinsulinemic rat and the ethanol-treated rat. The beneficial effects of taurine were also demonstrated in studies involving human subjects suffering essential hypertension. Taurine supplementation of 6 g/day for as little as 7 days resulted in measurable decreases in blood pressure in these patients. In both rat and human studies, the effects of taurine appeared to be dependent on the modulation of an overactive sympathetic system. However, taurine has positive effects on other types of cardiovascular problems and thus may act through more than one mechanism.

Abstract: 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, β-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% β-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. β-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 β-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 β-alanine. Muscle myeloperoxidase (MPO) activity was significantly elevated in the gastrocnemius muscle, but diet had no effect. MPO activity was significantly increased by exercise in the liver and both taurine and β-alanine blocked this effect. There was no effect of either exercise or the diets on MPO activity in the lung or spleen. Running performance as assessed by a subjective rating scale was improved by taurine supplementation and there was a significant loss in body weight in the β-alanine-treated rats 24 hours after exercise. In summary, taurine supplementation or taurine depletion had measurable cytoprotective actions to attenuate exercise-induced injury.

Abstract: In liver, cysteine dioxygenase (CDO), cysteinesulfinate decarboxylase (CSD), and gamma-glutamylcysteine synthetase (GCS) play important regulatory roles in the metabolism of cysteine to sulfate, taurine and glutathione. Because glutathione is released by the liver and degraded by peripheral tissues that express gamma-glutamyl transpeptidase, some peripheral tissues may be exposed to relatively high concentrations of cysteine. Rats were fed diets that contained low, moderate or high concentrations of protein or supplemental cysteine or methionine for 2 wk, and CDO, CSD and GCS activities, concentrations and mRNA levels and the concentrations of cysteine, taurine and glutathione were measured in liver, kidney, lung and brain. All three enzymes in liver responded to the differences in dietary protein or sulfur amino acid levels, but only CSD in kidney and none of the three enzymes in lung and brain responded. Renal CSD activity was twice as much in rats fed the low protein diet as in rats fed the other diets. Changes in renal CSD activity were correlated with changes in CSD concentration. Some significant differences in cysteine concentration in kidney and lung and glutathione and taurine concentrations in kidney were observed, with higher concentrations in rats fed higher levels of protein or sulfur amino acids. In liver, the changes in cysteine level were consistent with cysteine-mediated regulation of hepatic CDO activity, and changes in taurine level were consistent with predicted changes in cysteine catabolism due to the changes in cysteine concentration and CDO activity. Changes in renal and lung cysteine, taurine or glutathione concentrations were not associated with a similar pattern of change in CDO, CSD or GCS activity. Overall, the results confirm the importance of the liver in the maintenance of cysteine homeostasis.

Abstract: The process of wound healing begins immediately following surface lesions or just after exposure to radiation, chemical agents or extreme temperatures. Taurine (2-aminoethane sulfonic acid), an amino acid containing sulfur, is found in almost all tissues in mammals, playing various important physio-logical roles in each organ. Taurine exhibits an antioxidant effect and is also known to have effects on cell proliferation, inflammation and collagenogenesis. Many antioxidants have been used to eliminate the negative effects of oxygen free radicals on wound healing. The objective of the present study was to examine the wound healing effect in mice of taurine-chitosan gel, which releases taurine slowly over a long time period. Fifty mM of taurine in 1.5% chitosan polymer (TAU-GEL) and 1.5% chitosan polymer (CHI-GEL) were applied to full thickness skin wounds of mice once a day for seven days. After seven days of treatment, lipid peroxide formation-malondialdehyde (MDA) and hydroxyproline (HPX) levels and the tensile strength of wound tissues were measured. All results were compared with those of the untreated control group (CONT). The structural alterations in the skin layers were also histologically investigated. It was found that locally administered TAU-GEL form significantly increased wound tensile strength by decreasing the MDA and increasing HPX levels. These results were supported by histological findings. All observations suggest that taurine gel may be effective in wound healing.

Abstract: Neonatal rat primary astrocyte cultures were swollen by exposure to hypotonic buffer. Using an electrical impedance method for determination of cell volume coupled with on-line measurements of efflux of radioactive ions or amino acids, we have investigated the role of K+ (using 86Rb), taurine, and D-aspartate (an analogue of glutamate) in regulatory volume decrease (RVD). Addition of 1 mM quinine, 10 microM nimodipine, 100 microM BAPTA-AM, 10 microM trifluoperazine, or a calcium-free buffer significantly (p < 0.0001) inhibited RVD. This was accompanied by inhibition of 86Rb release but an increase in D-[3H]-aspartate release, which was proportional to the degree to which RVD was inhibited. These results support a regulatory role for calcium in RVD and show that inhibition of calcium entry from the extracellular fluid, intracellular calcium sequestration, inhibition of calcium-activated K+ channels, and inhibition of calmodulin all inhibit RVD. Because D-[3H]aspartate efflux profiles increase as RVD is inhibited, it is unlikely that D-aspartate release is a main determinant of RVD. In contrast, [3H]taurine release was increased by 1 mM quinine and inhibited by 10 microM trifluoperazine. The net release of K+ and taurine is highly correlated with the degree of RVD, implicating a regulatory role for both K+ and taurine release in RVD.

Abstract: Background Hyperglycemia selectively triggers apoptosis in tubule and endothelial cells. Taurine, a conditionally essential amino acid, is abundant in several tubule segments, but its role has not been defined fully. It can serve as an osmolyte or as an endogenous antioxidant. Taurine metabolism is altered in diabetes mellitus, with extracellular and intracellular pools reduced. It is still unknown whether taurine can play a role as a protective agent in apoptosis induced by high glucose in tubular cells. Methods Apoptosis (by annexin V binding and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method), cellular reactive oxygen species (ROS) formation (by fluorescent probe 2′-7′ dichlorofluorescin diacetate and FACScan flow cytometry), and Bcl-2 and Bax proteins (by immunostaining) were studied in a human proximal tubular cell line (HK-2) grown in a medium with physiologic (5.5 mM) or high (30 mM) glucose concentrations for 48 hours. In separate experiments, taurine (3-24 mM) was added to the media. Results The exposure of human tubule cells to 30 mM glucose for 48 hours resulted in a significant increase in apoptosis compared with 5.5 mM glucose (35±8% vs. 6±3%, p Conclusion These results demonstrate that taurine attenuates hyperglycemia-induced apoptosis in human tubular cells via an inhibition of oxidative stress. Taurine might act as an endogenous antioxidant in tubule cells and could exert a beneficial effect in preventing tubulointerstitial injury in diabetic nephropathy.

Abstract: The aim of this study was to elucidate the mechanisms by which retinal cells release endogenous amino acids in response to ascorbate/Fe 2+ -induced oxidative stress, as compared with chemical hypoxia or ischemia. In the absence of stimulation, oxidative stress increased the release of aspartate, glutamate, taurine, and GABA only when Ca 2+ was present. Under hypoxia or ischemia, the release of aspartate, glutamate, glycine, alanine, taurine, and GABA increased mainly by a Ca 2+ -independent mechanism. The increased release observed in N-methyl-D-glucamine + medium suggested the reversal of the Na + -dependent amino acid transporters. Upon oxidative stress, the release of aspartate, glutamate, and GABA, occurring through the reversal of the Na + -dependent transporters, was reduced by about 30%, although the release of taurine was enhanced. An increased release of [ 3 H]arachidonic acid and free radicals seems to affect the Na + -dependent transporters for glutamate and GABA in oxidized cells. All cell treatments increased [Ca 2+ ] i (1.5 to twofold), although no differences were observed in membrane depolarization. The energy charge of cells submitted to hypoxia or oxidative stress was not changed. However, ischemia highly potentiated the reduction of the energy charge, as compared with hypoglycemia or hypoxia alone. The present work is important for understanding the mechanisms of amino acid release that occur in vivo upon oxidative stress, hypoxia, or ischemia, frequently associated with the impairment of energy metabolism.

Abstract: Taurine, a non-protein sulfur amino-acid, is the most abundant free amino-acid in the body and plays an important role in several essential biological processes. Apart from its role in cholesterol degradation, it acts as neurotransmitter, and has a function as osmoregulator and antioxidant in most body tissues. During pregnancy, taurine accumulates in the maternal tissues, to be released in the perinatal period to the fetus via the placenta and to the newborn via the maternal milk. It is accumulated especially in the fetal and neonatal brain. Low maternal taurine levels result in low fetal taurine levels. Taurine-deficiency in the mother leads to growth retardation of the offspring, and to impaired perinatal development of the central nervous system and of the endocrine pancreas. The adult offspring of taurine-deficient mothers display signs of impaired neurological function, impaired glucose tolerance and vascular dysfunction; they may develop gestational diabetes and transmit the effects to the next generation. This transgeneration effect of taurine-deficiency in the perinatal period fits into the concept of fetal origin of adult disease.

Abstract: Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin-diabetic rats fed standard or 1% T-supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were quantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phase HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean +/− SEM) was increased in diabetic rats (0.127 +/−0.006 vs 0.053 +/−0.003 mu mol/g in controls, P<0.01), and this increase was partially prevented by T (0.0960.004, P<0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P<0.05 vs controls). AA levels were decreased in diabetic rats (0.133+0.015 vs 0.219 +/−0.023 mu mol/g in controls, P<0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P<0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/−0.16 vs 3.8 +/−0.1 mu mol/g in controls, P<0.05) and were repleted by T supplementation (4.20.3). NGF levels were decreased in diabetic rats (2.35 +/−0.20 vs 3.57 +/−0.20 ng/g in controls, P<0.01), and this decrease was attenuated by T treatment (3.160.28, P<0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.

Abstract: 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., GABAA and glycine receptors) as well as inhibitory effects on other ligand- and voltage-gated cation channels (i.e., NMDA and Ca2+ 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.

Abstract: The effect of a high-cholesterol diet with or without taurine on lipids and oxidative stress in the plasma, liver and aorta of rabbits was investigated. The animals were maintained on a basal diet (control), a high-cholesterol diet (HC, 1% w/w), or a high- cholesterol diet supplemented with taurine (HCHT, 2.5% w/w) for two months. Taurine has an ameliorating effect on atherosclerosis together with a decreasing effect on the cholesterol and triglyceride levels in rabbits fed on an HC diet. The HCHT diet caused a significant decrease in the malondialdehyde (MDA) and diene conjugate (DC) levels in the plasma, liver and aorta of rabbits as compared to the HC group. This treatment did not alter the antioxidant system in the liver of rabbits in the HC group. Our findings indicate that taurine ameliorated oxidative stress and cholesterol accumulation in the aorta of rabbits fed on the HC diet and that this effect may be related to its antioxidative potential as well as its reducing effect on serum lipids.

Abstract: SUMMARY The composition of the intestinal lumen is likely to have considerable influence upon the absorption, and consequently the nutrition and/or toxicity, of ingested zinc in aquatic environments, where zinc is both a nutrient and a toxicant of importance The effects of amino acids upon intestinal zinc uptake in freshwater rainbow trout ( Oncorhynchus mykiss ) were studied using an in vivo perfusion technique The presence of histidine, cysteine and taurine had distinct modifying actions upon quantitative and qualitative zinc absorption, compared to perfusion of zinc alone Alterations in zinc transport were not correlated with changes in levels of free zinc ion The chemical nature of the zinc–amino acid chelate, rather than the chelation itself, appeared to have the most important influence upon zinc absorption l-histidine, despite a strong zinc-chelating effect, maintained quantitative zinc uptake at control (zinc alone) levels This effect correlated with the formation of Zn(His) 2 species d-histidine at a luminal concentration of 100 mmol l –1 significantly enhanced subepithelial zinc accumulation, but reduced the fraction of zinc that was retained and absorbed by the fish The possibility of a Zn(His) 2 -mediated pathway for intestinal uptake is discussed l-cysteine specifically stimulated the accumulation of zinc post-intestinally, an effect attributed to enhanced zinc accumulation in the blood Taurine increased subepithelial zinc accumulation, but decreased the passage of zinc to post-intestinal compartments Amino acids are proposed to have important roles in modifying intestinal zinc uptake with potential implications for environmental toxicity as well as aquaculture

Abstract: HPLC and gas chromatography-mass spectrometry analyses of 18 amino acids, N-acetylaspartate, N-acetylaspartylglutamate, and 5-hydroxyindoleacetic acid, derived from serotonin, and homovanillic acid, derived from dopamine, were performed in CSF collected from a group of patients with schizophrenia who either had been drug free for at least 1 year (n = 5) or were drug naive for psychotropic drugs (n = 21) and in 15 control subjects. Significant differences were found only for taurine (15% lower in the patients) and isoleucine (7% higher). A number of unidentified substances were detected, one of which proved to be markedly reduced (16%) among the schizophrenic patients. Liquid chromatography-mass spectrometry with continuous flow-fast atom bombardment interface allowed us to identify this substance as gamma-glutamylglutamine. The decreased level of gamma-glutamylglutamine may reflect a deficiency in the gamma-glutamyltransferase system, a system probably involved in glutamate uptake, or a deficiency in glutamine, an important precursor of releasable glutamate. Although glutamate was nonsignificantly reduced in the patients, it was one of the five substances (including gamma-glutamylglutamine) that were necessary for the best discrimination between the schizophrenic patients and the controls. These findings support the notion that the glutamatergic system is affected in schizophrenic disorders. In addition, they underscore the need to apply rigid bioanalytical techniques and use drug-naive patients to gain in-depth information on the pathophysiology of brain disorders such as schizophrenia.

Abstract: The role of Rho GTPases in the regulatory volume decrease (RVD) process following osmotic cell swelling is controversial and has so far only been investigated for the swelling-activated Cl− efflux. We investigated the involvement of RhoA in the RVD process in NIH3T3 mouse fibroblasts, using wild-type cells and three clones expressing constitutively active RhoA (RhoAV14). RhoAV14 expression resulted in an up to fourfold increase in the rate of RVD, measured by large-angle light scattering. The increase in RVD rate correlated with RhoAV14 expression. RVD in wild-type cells was unaffected by the Rho kinase inhibitor Y-27632 and the phosphatidyl-inositol 3 kinase (PI3K) inhibitor wortmannin. The maximal rates of swelling-activated K+ (86Rb+ as tracer) and taurine ([3H]taurine as tracer) efflux after a 30 % reduction in extracellular osmolarity were increased about twofold in cells with maximal RhoAV14 expression compared to wild-type cells, but were unaffected by Y-27632. The volume set points for activation of release of both osmolytes appeared to be reduced by RhoAV14 expression. The maximal taurine efflux rate constant was potentiated by the tyrosine phosphatase inhibitor Na3VO4, and inhibited by the tyrosine kinase inhibitor genistein. The magnitude of the swelling-activated Cl− current (ICl,swell) was higher in RhoAV14 than in wild-type cells after a 7.5 % reduction in extracellular osmolarity, but, in contrast to 86Rb+ and [3H]taurine efflux, similar in both strains after a 30 % reduction in extracellular osmolarity. ICl,swell was inhibited by Y-27632 and strongly potentiated by the myosin light chain kinase inhibitors ML-7 and AV25. It is suggested that RhoA, although not the volume sensor per se, is an important upstream modulator shared by multiple swelling-activated channels on which RhoA exerts its effects via divergent signalling pathways.

Abstract: In this study, we evaluated whether taurine treatment has a protective effect on the prooxidant-antioxidant state following chronic ethanol treatment in rats. Rats were given water containing 20% ethanol (v/v) as drinking water for 3 months. Chronic ethanol treatment in drinking water resulted in increased oxidative stress in the liver of rats. Taurine treatment was performed by adding 1% taurine (w/v) to the drinking water plus injection (400 mg/kg body weight) intraperitoneally 3 times/week for 28 d after ethanol cessation in chronically ethanol-treatad rats. This treatment starting after ethanol cessation caused a significant decreases in serum transaminase activities and hepatic total lipid, triglyceride, malondialdehyde, and diene conjugate levels and significant increases in hepatic glutathione, vitamin E, and vitamin C levels, but did not alter the activities of superoxide dismutase, glutathione peroxidase, and glutathione transferase in the liver as compared with chronically ethanol-treated rats. Accordingly, we propose that taurine has a restorative effect on ethanol-induced hepatic damage by decreasing oxidative stres.

Abstract: The synthesis of hypotaurine and taurine was investigated in astroglia-rich primary cultures obtained from brains of neonatal Wistar rats using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Cell extracts of astroglial cultures analyzed by 1H NMR spectroscopy show prominent signals of hypotaurine. To identify cysteine as precursor for hypotaurine and taurine synthesis in astroglial cells, primary cultures were incubated with [3-(13)C]cysteine for 24 or 72 h. Cell extracts and incubation media were then analyzed with 13C NMR spectroscopy. Labeled hypotaurine, taurine, glutathione, and lactate were identified in the cell extracts. Within 72 h, 35.0% of the total intracellular hypotaurine and 22.5% of taurine were newly synthesized from [3-(13)C] cysteine. The presence of [1-(13)C]hypotaurine and [1-(13)C]taurine in the incubation medium proves the release of those products of cysteine metabolism into the medium. Minor amounts of the [3-(13)C]cysteine were used for the synthesis of glutathione in astroglial cells or metabolized to [3-(13)C]lactate, which was found in cell extracts and media. These results indicate that the formation of hypotaurine and taurine is a major pathway of cysteine metabolism in astroglial cells.

Abstract: 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.

Abstract: MATSUZAKI, Y., T. MIYAZAKI, S. MIYAKAWA, B. BOUSCAREL, T. IKEGAMI, and N. TANAKA. Decreased taurine concentration in skeletal muscles after exercise for various durations. Med. Sci. Sports Exerc., Vol. 34, No. 5, pp. 793–797, 2002. Purpose: To examine the changes of taurine concentrations in blood and skeletal muscles after transient exercise. Methods: Rats were placed on a treadmill set at 25 m·min 1 . The animals were divided into four groups: control (no exercise) and exercise groups 1, 2, and 3. The exercise duration for groups 1, 2, and 3 was 30, 60, and 100 12.5 min (to exhaustion: mean SD), respectively. We examined the plasma concentrations of taurine and lactate, the serum concentrations of sodium and chloride ions, as well as the skeletal muscle taurine content in the soleus (slow-twitch fiber dominant type), gastrocnemius (slow- and fast-twitch fiber mix type), and plantaris and extensor digitorum longus (fast-twitch fiber dominant type) muscles. Results: Although the plasma taurine concentration was not affected by the increased exercise duration, that in skeletal muscles was significantly decreased. The gastrocnemius and plantaris muscles from the exercise group 3 had a significantly lower concentration of taurine than those of the control group. The extensor digitorum longus taurine concentration from the different exercise groups was significantly decreased compared with that from the control group. However, there was no significant difference among the exercise groups. Conclusion: Taurine concentration was decreased in all skeletal muscles after exercise, regardless of the duration. Moreover, this decrease was specific to fast-twitch dominant

Abstract: This study evaluates the effect of 4 months supplementation with 2% and 5% taurine (w/w) on the retina of diabetic rats. In non-diabetic rats, taurine does not modify glycemia, body weight, retinal conjugated dienes (CD), lipid hydroperoxide (LP), and Na+K+ATPase activity. In diabetic rat, at 2, 4, 8, 16 weeks following the onset of diabetes, retinal CD and LP are significantly and progressively increased, while pump activity is gradually and significantly reduced. In taurine supplemented diabetic rats, glycemia is not affected but lipid peroxidation is significantly decreased. Finally, taurine preserves ATPase activity being 5% more effective than 2% taurine. We conclude that taurine supplementation ameliorates biochemical retinal abnormalities caused by diabetes, thereby suggesting that taurine may have a role in the prevention of retinal changes in diabetes.