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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.23, #4)


Interactions between taurine and ethanol in the central nervous system by M. F. Olive (pp. 345-357).
 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.

Keywords: Keywords: Taurine; Ethanol; Locomotor activity; Sedation; self-administration; Acamprosate; Central nervous system (CNS)


The regulation of sulphurated amino acid junctionsFact or fiction in the field of inflammation? by F. Santangelo (pp. 359-365).
 The diet of industrialised countries is usually rich in amino acids, which are in part used as a source of calories. However, metabolic alterations are observed in diseased patients and a preferential retention of Sulphurated Amino Acids (SAA) occurs during the inflammatory response. Moreover, it has been demonstrated in a model of an acute sepsis phase of rats that the metabolism of Cysteine is modified. The liver converts Cysteine at a different ratio of Sulphate to Taurine (Tau) i.e. the sulphate production decreases while the Tau conversion increases. The Glutathione (GSH) concentration is greater in the liver, kidneys and other organs and the Cysteine incorporation into proteins is higher in the spleen, lungs and plasma (Acute Phase Proteins) while the Albumin level decreases. The pro-inflammatory cytokines such as Interleukin-1, Interleukin-6 and TNF-α are the main initiators that alter protein and amino acid metabolism.Another important phenomenon is the impairment of Methionine conversion to Cysteine during stress. For example, premature infants or AIDS patients are capable of synthesizing Cysteine from Methionine at a much lower rate. Thus, the metabolic flow through the trans-sulphuration path may be inadequate to meet the Cysteine demand under critical conditions.In this complex picture, an SAA supply may contribute to an immune system regulation.

Keywords: Keywords: Acute Phase Reaction; Cysteine; Glutathione; N-Acetylcysteine; Metabolism; Taurine


The use of taurine analogues to investigate taurine functions and their potential therapeutic applications by L. Della Corte; R. R. Crichton; G. Duburs; K. Nolan; K. F. Tipton; G. Tirzitis; R. J. Ward (pp. 367-379).
 Despite the multitude of evidence for the beneficial effects of taurine supplementation in a variety of disease, the underlying modifying action of taurine with respect to either molecular or biochemical mechanisms is almost totally unknown. We have assessed the development of taurine analogues, particularly where there has been substitution at the suphonate or amine group. Such substitutions allow the investigator to probe the relationship between structure and function of the taurine molecule. In addition such studies should help to ascertain taurine's point of interaction with the effector molecule. These results will prepare the way for the development of the second generation of taurine analogues.

Keywords: Keywords: Taurine analogues; Neurotransmitter; Neuromodulation; Antioxidant


Treatment of hypertension with oral taurine: experimental and clinical studies by J. D. Militante; J. B. Lombardini (pp. 381-393).
 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.

Keywords: Keywords: Hypertension; Taurine supplementation; Experimental models; Modulation of overactive sympathetic system


Effect of ischemia, calcium depletion and repletion, acidosis and hypoxia on cellular taurine content by S. W. Schaffer; V. Pastukh; V. Solodushko; J. Kramer; J. Azuma (pp. 395-400).
 Occlusion of the left main coronary artery led to a time-dependent release of taurine from the heart. Upon reperfusion, there was a second phase of taurine release, which exceeded the amount of taurine that exited the heart during the 45 min ischemic insult. To obtain information on the mechanism underlying the release of taurine, three variables were examined, acidosis, hypoxia and calcium overload. It was found that large amounts of taurine also leave the cell during the calcium paradox, a condition induced by perfusing the heart with calcium containing buffer following a period of calcium free perfusion. However, little taurine effluxes the hearts exposed to buffer whose pH was lowered to 6.6. Isolated neonatal cardiomyocytes subjected to chemical hypoxia also lost large amounts of taurine. However, the amount of taurine leaving the cells appeared to be correlated with the intracellular sodium concentration, [Na+]i. The data suggest that taurine efflux is regulated by [Na+]i and cellular osmolality, but not by cellular pH.

Keywords: Keywords: Amino acids; Taurine content; Ischemia; Calcium paradox; Acidosis; Hypoxia; Sodium concentration; Osmolality


Chronic taurine supplementation ameliorates oxidative stress and Na + K + ATPase impairment in the retina of diabetic rats by M. A. S. Di Leo; S. A. Santini; S. Cercone; D. Lepore; N. Gentiloni Silveri; S. Caputo; A. V. Greco; B. Giardina; F. Franconi; G. Ghirlanda (pp. 401-406).
 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.

Keywords: Keywords: Diabetes mellitus; Lipid peroxidation; Glycemia; Streptozotocin; Na+K+ATPase


Taurine chloramine modulates cytokine production by human peripheral blood mononuclear cells by M. Chorąży; E. Kontny; J. Marcinkiewicz; W. Maśliński (pp. 407-413).
 The effect of taurine (Tau) and taurine chloramine (Tau-Cl) on the production of TNF-α, IL-1β, and IL-6 by peripheral blood mononuclear cells of healthy volunteers was examined. Cells were stimulated with bacterial lipopolysaccharide (LPS) in the presence of either Tau or Tau-Cl. After 24 h culture the cytokine concentrations were measured in both culture supernatants (secreted) and cell lysates (cell-associated) using ELISA. In LPS-stimulated cells Tau-Cl inhibited both the secreted and cell-associated IL-1β and IL-6, while exerted dual effect on TNF-α production: raising it slightly at low and reducing at higher concentration. By contrast, Tau had no significant effect on the cytokine production. These results indicate that Tau-Cl modulates synthesis of pro-inflammatory cytokines, and therefore it may play a role in the initiation and propagation of immune response.

Keywords: Keywords: Taurine chloramine; TNF-α; IL-1β; IL-6; Peripheral blood mononuclear cells


Impaired generation of taurine chloramine by synovial fluid neutrophils of rheumatoid arthritis patients by E. Kontny; E. Wojtecka-Łukasik; K. Rell-Bakalarska; W. Dziewczopolski; W. Maśliński; S. Maślinski (pp. 415-418).
 Taurine (Tau), a dominant free amino acid present in neutrophil cytoplasm, serves as a scavenger for hypochlorous acid (HOCl) released during these cells activation. The resulting taurine chloramine (Tau-Cl) exerts potent anti-inflammatory properties. In the present study we tested the hypothesis that the formation of Tau-Cl is impaired in neutrophils isolated from rheumatoid arthritis (RA) patients. The inhibition of zymosan-triggered chemiluminescence in the presence of exogenous Tau was used for indirect measurement of Tau-Cl generation. The chemiluminescence of neutrophils isolated from peripheral blood (PB) of healthy volunteers and RA patients was inhibited by Tau with similar potency. By contrast, synovial fluid (SF) neutrophils of these patients were significantly less sensitive for Tau-mediated inhibition. Therefore, our data indicate impaired generation of Tau-Cl in neutrophils isolated from SF of RA patients.

Keywords: Keywords: Rheumatoid arthritis; Synovial fluid neutrophils; Taurine chloramine


Effect of taurine chloramine, the product of activated neutrophils, on the development of collagen-induced arthritis in DBA 1/J mice by B. Kwaśny-Krochin; M. Bobek; E. Kontny; P. Gluszko; R. Biedroń; B. M. Chain; W. Maśliński; J. Marcinkiewicz (pp. 419-426).
 Taurine chloramine (TauCl), a product of neutrophil myeloperoxidase – halide system, formed by a reaction of taurine with HOCl, is known as an anti-microbial and anti-inflammatory long-lived oxidant. We previously reported that TauCl inhibits in vitro the production of proinflammatory cytokines (IL-6, IL-8) by RA synoviocytes. Therefore we performed this study to investigate the effect of TauCl treatment on the development of collagen-induced arthritis (CIA) in DBA1/J mice. Early administration of TauCl (after primary immunization) resulted in the delay of the onset of CIA, but had no effect on severity of arthritis. TauCl, given daily for 21 days after booster immunization, did not reduce the symptoms of arthritis in those mice, which already developed CIA, but significantly diminished incidence of the disease (55% vs. 90% of placebo mice). The mechanism of this effect is unknown. This is the first in vivo study suggesting that TauCl may be used for immune intervention in chronic inflammatory diseases.

Keywords: Keywords: Taurine chloramine; Neutrophils; Collagen induced arthritis; DBA 1/J mice


A study on the estimation of sulfur-containing amino acid metabolism by the determination of urinary sulfate and taurine by H. Nakamura; R. Kajikawa; T. Ubuka (pp. 427-431).
 Sulfate and taurine are major end products of sulfur-containing amino acid metabolism in mammals including humans, and they are excreted in urine. Average excretions (μmol/mg of creatinine) in the morning urine of 58 female college students were: total (free plus ester) sulfate (a), 12.53 ± 3.85; free sulfate, 11.57 ± 3.69; taurine, 0.78 ± 0.53. Ratio of total sulfate and taurine was 10 : 0.6. Regression lines obtained by plotting total sulfate, free sulfate, or total sulfate plus taurine against urea have shown that the former excretions are significantly correlated with urea excretion. Excretion of total sulfate at zero point of urea excretion (b) was 5.30, which corresponded to 42.3% of average excretion (12.53) and was assumed to be derived from dietary sulfate. The difference 7.23 (a − b) seemed to be derived from sulfur-containing amino acids. It was pointed out that the difference of average sulfate excretion and sulfate excretion at zero urea excretion, namely a − b, was appropriate for the metabolic index of sulfur-containing amino acids of the group examined. As free sulfate constituted 92.3% of total sulfate, excretion of ester sulfate was at a constant level, and that of taurine was not significantly correlated with urea excretion, the value of free sulfate corresponding to the value a − b of total sulfate mentioned above seemed to be a reliable and convenient index in the assessment of sulfur-containing amino acid metabolism.

Keywords: Keywords: Amino acids; Sulfur-containing amino acids; Sulfate; Taurine; Metabolic index


Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet by H. Yokogoshi; H. Oda (pp. 433-439).
 The effect of taurine on hypercholesterolemia induced by feeding a high-cholesterol (HC) diet (10 g/kg) to rats was examined. When taurine was supplemented to HC for 2 wk, serum total cholesterol significantly decreased and serum HDL-cholesterol increased compared with the HC diet group. In the hypercholesterolemic rats fed the HC diet, the excretion of fecal bile acids and hepatic cholesterol 7α-hydroxylase (CYP7A1) activity and its mRNA level increased significantly, and the supplementation of taurine further enhanced these indexes, indicating an increase in cholesterol degradation. Agarose gel electrophoresis revealed that, in hypercholesterolemic rats fed the HC diet, the serum level of the heavier VLDL increased significantly, but taurine repressed this increase and normalized this pattern. Significant correlations were observed between the time-dependent increase of CYP7A1 gene expression and the decrease of blood cholesterol concentration in rats fed the HC diet supplemented with taurine. These results suggest that the hypocholesterolemic effects of taurine observed in the hypocholesterolemic rats fed the HC diet were mainly due to the enhancement of cholesterol degradation and the excretion of bile acid.

Keywords: Keywords: Taurine; Cholesterol; Hypocholesterolemia; Cholesterol 7α-hydroxylase (CYP7A1); Rat


Effects of taurine on polymorphonuclear phagocytosis activity in burned patients by M. Farriol; Y. Venereo; J. Rosselló; P. Gomez; R. Palao; X. Orta; T. Segovia-Silvestre (pp. 441-445).
 This study determines the effects of taurine (Tau) on phagocytosis of polymorphonuclear neutrophils (PMN) isolated from normal subjects (n = 41) and severely burned patients (n = 20). Phagocytosis was measured by nitroblue of tetrazolium (NBT) reduction in samples with and without latex bead stimulation. Taurine was added at doses of 0.2, 0.4, 0.8 and 1.6 mM to stimulated samples. In control cells there were statistically significant increases in phagocytosis after addition of Tau 0.8 mM and 1.6 mM to as compared to samples without Tau addition (295 ± 23% and 330 ± 35% vs. 248 ± 18%; mean ± S.E.; p < 0.05). A statistically significant increase in phagocytosis was observed in cells from the burned population after addition of Tau 1.6 mM (288 ± 38% vs. 198 ± 13%; mean ± S.E.; p < 0.05). No changes in phagocytosis were found in cells from a subgroup of burn patients (n = 13) followed over 7, 15 and 21 days. These results indicate that taurine supplementation in vitro at doses of 0.8 to 1.6 mM improves the phagocytic capacity of neutrophils in healthy subjects and in patients with severe burn injury, mainly when neutrophil function is unaltered.

Keywords: Keywords: Phagocytosis; Taurine; Neutrophils; NBT


Effect of dietary sulfur amino acids on the taurine content of rat tissues by H. Satsu; Y. Kobayashi; T. Yokoyama; E. Terasawa; M. Shimizu (pp. 447-452).
 The effect of dietary sulfur amino acids on the taurine content of rat blood and tissues was investigated. Three types of diet were prepared for this study: a low-taurine diet (LTD), normal taurine diet (NTD; LTD + 0.5% Met), and high-taurine diet (HTD; LTD + 0.5% Met + 3% taurine). These diets had no differing effect on the growth of the rats. The concentration of taurine in the blood from the HTD- and NTD-fed rats was respectively 1,200% and 200% more than that from LTD-. In such rat tissues as the liver, the taurine content was significantly affected by dietary sulfur amino acids, resulting in a higher content with HTD and lower content with LTD. However, little or no effect on taurine content was apparent in the heart or eye. The activity for taurine uptake by the small intestine was not affected by dietary sulfur amino acids. The expression level of taurine transporter mRNA was altered only in the kidney under these dietary conditions: a higher expression level with LTD and lower expression level with HTD.

Keywords: Keywords: Taurine; Sulfur amino acid; Transporter; Adaptive response


Cysteine metabolism in periportal and perivenous hepatocytes: Perivenous cells have greater capacity for glutathione production and taurine synthesis but not for cysteine catabolism by D. L. Bella; L. L. Hirschberger; Y. H. Kwon; M. H. Stipanuk (pp. 453-458).
 Hepatocyte preparations highly enriched in cells from either the periportal or the perivenous zone of the liver acinus were prepared using a digitonin/collagenase perfusion method. Five enzymes of cysteine metabolism were assayed in both periportal and perivenous preparations. The ratios of periportal to perivenous activity were 0.76, 0.60, 0.81, 1.62, and 1.01 for cysteine dioxygenase, cysteinesulfinate decarboxylase, γ-glutamylcysteine synthetase, cystathionase, and asparate (cysteinesulfinate) aminotransferase, respectively. Only cysteinesulfinate decarboxylase activity was significantly different between periportal and perivenous cells. In incubations with 2 mmol/L [35S]cysteine, total cysteine catabolism ([35S]taurine plus [35S]sulfate) between periportal and perivenous cells was not different, which is consistent with the observation of similar cysteine dioxygenase activity across the hepatic acinus. Consistent with the lower cysteinesulfinate decarboxylase activity in periportal cells, 16% of the total catabolism of [35S]cysteine in periportal cells resulted in taurine synthesis compared to 28% in perivenous cells. A lower rate of [35S]glutathione synthesis was observed in periportal cells compared to perivenous cells, but γ-glutamylcysteine synthetase activity was not significantly different between perivenous and periportal cells. Cysteinesulfnate decarboxylase can be added to the list of enzymes whose activities are markedly enriched in perivenous cells.

Keywords: Keywords: Cystathionase; Cysteine dioxygenase; Cysteinesulfinate decarboxylase; γ-Glutamylcysteine synthetase; Periportal hepatocytes; Perivenous hepatocytes

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