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

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.

Caco-2 Cells↗

Effects of long-term treatment with taurine in mice fed a high-fat diet: improvement in cholesterol metabolism and vascular lipid accumulation by taurine.

Hypocholesterolemic effects of taurine in rats fed a high-fat and high-cholesterol diet are well established. However, there are few studies on long-term effects of taurine on cholesterol metabolism. In the present study, taurine was dissolved in drinking water and given to C57BL/6J mice during 6 months-feeding of a high fat diet. Taurine treatment significantly decreased serum LDL and VLDL cholesterol, while it significantly increased serum HDL cholesterol. In the liver, taurine decreased cholesteryl ester contents, accompanied by decrease in acyl CoA:cholesterol acyltransferase (ACAT) activity. Hepatic activity of cholesterol 7alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis, was doubled with taurine. Taurine reduced by 20% the high-fat diet-induced arterial lipid accumulation. Thus, taurine prevented elevation of serum and liver cholesterol levels, as possibly related to accelerated cholesterol elimination from the body through the stimulation of bile acid synthesis. Long-term treatment with taurine is beneficial for prevention of hypercholesterolemia and atherosclerosis.

Animals↗

Studies on renal adaptation to altered dietary amino acid intake: reduced renal cortex taurine content increases the Vmax of taurine uptake by brush border membrane vesicles.

Rats were placed on a normal taurine diet (NTD), low taurine diet (LTD) or a high taurine diet (HTD) for 14 days. beta-Alanine was fed to half of the animals in each group and resulted in a lowered renal cortex taurine content. Brush border membrane vesicle (BBMV) uptake of taurine was higher after beta-alanine feeding and was associated with an increase in Vmax of uptake. beta-Alanine feeding to HTD animals also altered the Km of uptake, possibly since the load of sulfur amino acids (6% of diet) was high. As a control, glycine (3%) feeding for 8 days along with each diet did not alter the plasma or renal cortex content; BBMV uptake as well as Km and Vmax of taurine accumulation were minimally altered. Accordingly, ingestion of a non-sulfur-containing alpha-amino acid did not change beta-amino acid transport. This study provides evidence that whole body taurine homeostasis is maintained in the presence of a taurine-depleting agent (beta-alanine feeding) by an increase in the number of Na(+)-taurine uptake sites.

Amino Acids↗

Taurine, a possible urinary marker of liver damage: a study of taurine excretion in carbon tetrachloride-treated rats.

Carbon tetrachloride (CCl4) caused a dose-dependent increase in urinary taurine which correlated with both the histological and biochemical assessment of liver damage. The peak elevation in urinary taurine occurred within the first 48 h after dosing but there was still significant taurinuria 72 and 96 h after the intermediate dose (1 ml.kg-1) and highest dose (2 ml.kg-1), respectively. Levels of taurine in serum were also elevated over the 24 h period following a hepatotoxic dose (2 ml.kg-1) of CCl4. In contrast, although initially elevated, levels of taurine in the liver declined over the 24 h period following dosing and were significantly lower 96 h after a hepatotoxic dose of CCl4 (2 ml.kg-1). Male rats showed a different urinary profile for taurine than female rats after dosing with CCl4. A reduction in food intake seemed to lower urinary taurine levels although these changes were not statistically significant. There was a significant correlation between the level of urinary taurine and the level of serum AST for individual animals given a hepatotoxic dose of CCl4 (2 ml.kg-1). The data presented suggest that: i) taurine is produced by the liver in response to a toxic insult and subsequent leakage from damaged cells leads to increased levels in the urine; ii) the urinary taurine level may be a useful non-invasive marker of liver damage.

Alanine Transaminase↗

Inhibition by taurine of the phosphorylation of specific synaptosomal proteins in the rat cortex: effects of taurine on the stimulation of calcium uptake in mitochondria and inhibition of phosphoinositide turnover.

It has been previously observed that taurine inhibits PKC-activated phosphorylation of specific proteins including a approximately 20k Mr protein in rat cortical synaptosomes. In the present study, the mechanism of the above effects of taurine were investigated. In an intrasynaptosomal cytosol fraction obtained by subcellular fractionation, taurine did not have inhibitory effects on protein phosphorylation. However, taurine did inhibit the phosphorylation of the approximately 20k Mr protein in a reconstituted preparation containing intrasynaptosomal cytosol and mitochondria. Experiments measuring calcium uptake demonstrated that taurine increased the accumulation of 45Ca2+ in the mitochondrial fraction in incubation systems both in the absence and presence of added ATP. In addition, taurine inhibited the accumulation of 32P-labeled phosphatidic acid in synaptosomes indicative of a reduction in the levels of diacylglycerol. These results suggest that taurine may inhibit specific protein phosphorylation both by reducing cytosolic calcium levels and by inhibiting the turnover of phosphoinositides. These effects of taurine on the signal transduction cascade involving PKC and phosphoinositide metabolism indicate a potential biological role for taurine in the nervous system.

Adenosine Triphosphate↗

Ethanol-induced sleep time: interaction with taurine and a taurine antagonist.

In male Swiss-Webster mice sleep time (hypnosis) was used as an index of ethanol-induced central nervous system depression. Ethanol (4 g/kg, IP) was administered to animals and the onset to sleep time (loss of the righting reflex) and the duration of sleep time were recorded. At the end of the ethanol-induced sleep time, taurine (7.5, 15 or 25 mumol/kg, ICV) was injected. Immediately after the ICV injection of taurine the mice again lost the righting reflex. This effect of taurine occurred in a dose-dependent fashion. In the absence of ethanol, taurine (25 mumol/kg, ICV) did not produce a significant sleep time. In another experiment when TAG, 6-amino-methyl-3-4H-1,3,4-benzothiadiazine-1,1-dioxide HCl, (a taurine antagonist) was given to mice, TAG (0.9 mumol/kg, ICV) significantly reduced the effect of taurine (7.5, 15 and 25 mumol/kg, ICV) to reinstate a sleep time in the presence of ethanol. TAG, however, did not alter ethanol-induced sleep time. These results indicate that taurine (ICV) can enhance the central depressant action of ethanol and that this effect of taurine can be attenuated by TAG. The antagonism of taurine by TAG appears to be noncompetitive in nature.

Animals↗

Effect of taurine on cholesterol metabolism in hamsters: up-regulation of low density lipoprotein (LDL) receptor by taurine.

The effects of taurine on hepatic cholesterol metabolism were investigated in hamsters fed a high-fat diet or normal chow. Two weeks-treatment of taurine at 1% in drinking water prevented high-fat diet-induced increase in cholesterol levels of serum and liver. The decrease in serum cholesterol by taurine was due to decrease in non-HDL cholesterols. A similar tendency was noted in serum and liver cholesterol levels of hamsters fed a normal diet. In hamsters fed a high-fat diet, taurine prevented elevation in hepatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and increased the activity of cholesterol 7alpha-hydroxylase. Taurine also increased cholesterol 7alpha-hydroxylase activity in hamsters fed normal chow. Studies on liver membranes revealed that taurine increased 125I-labeled LDL binding by 52% and 58% in hamsters fed either a normal chow or high-fat diet, respectively. Furthermore, LDL kinetic analysis showed that taurine intake resulted in significant faster plasma LDL fractional catabolic rates (FCR). These results suggest that taurine elevates hepatic LDL receptor and thereby decreases serum cholesterol levels, an event which may be the result of hepatic cholesterol depletion as a consequence of increased bile acid synthesis via enhancement of cholesterol 7alpha-hydroxylase activity. Thus, up-regulation of the LDL receptor and subsequent increase in receptor- mediated LDL turnover may be a key event in the cholesterol-lowering effects of taurine in hamsters.

Animals↗

Taurine concentrations in animal feed ingredients; cooking influences taurine content.

The aim of this study was to determine the taurine content in a variety of animal feeds. There is very little information on the taurine content of ingredients used in home-prepared diets for dogs and cats, and foods fed to wild animals in captivity. This study reports the taurine content of both common and alternative feed ingredients, and compares taurine loss as a result of different methods of food preparation. Foods were selected based on their use in commercial and home-prepared diets. Animal muscle tissue, particularly marine, contained high taurine concentrations. Plant products contained either low or undetectable amounts of taurine. The amount of taurine that remained in a feed ingredient after cooking depended upon the method of food preparation. When an ingredient was constantly surrounded by water during the cooking process, such as in boiling or basting, more taurine was lost. Food preparation methods that minimized water loss, such as baking or frying, had higher rates of taurine retention.

Animal Feed↗

Effect of taurine deficiency on tissue taurine concentrations and pregnancy outcome in the rat.

Taurine status and pregnancy outcome were assessed in rats fed low dietary taurine and varying doses of guanidinoethyl sulfonate (GES), a structural analogue of taurine. Female Sprague-Dawley rats (225-270 g) were mated overnight and assigned to one of four groups from day 0 to 20 of gestation. Taurine-deficient animals were fed a basal diet containing < 0.001 mumol taurine/g and 0.5 (n = 7), 1.0 (n = 8), or 2.0% (n = 7) GES in their drinking water, ad libitum. Control animals (n = 8) received similar treatment, with 2 mumol taurine/g added to the diet and no GES in their water. Taurine was analyzed by reverse-phase HPLC, using electrochemical detection after precolumn derivatization with ortho-phthalaldehyde. Treatment of rats with varying doses of GES produced a sharp decline in maternal liver and brain taurine to 15 and 55% of that of control levels, and in fetal liver and brain taurine to 75 and 50% of that of control levels, respectively (p = 0.0001; one-way ANOVA). The 2% group had a smaller mean (+/- SEM) litter weight than the control group (35.8 +/- 6.1 vs. 51.9 +/- 2.8 g; p = 0.042) as a result of a smaller litter size. The decrease in litter size was associated with confinement of implantation sites to either the left or right uterine horn in four of seven dams. Taurine deficiency did not result in intrauterine growth retardation or significant external, visceral, or skeletal malformations. Developmental defects were not found in any of the taurine-deficient groups, but reproductive abnormalities were present at the highest dose of the analogue.

Animals↗

Interactions of NIP-taurine, NAP-taurine, and Cl- with the human erythrocyte anion exchange system.

N-(4-isothiocyano-2-nitrophenyl)-2-aminoethanesulfonate (NIP-taurine), a newly synthesized isothiocyano derivative of N-(4-azido-2-nitrophenyl)-2-aminoethanesulfonate (NAP-taurine), is a potent inhibitor of human erythrocyte chloride exchange. At 0 degrees C, the inhibition is reversible, but at 37 degrees C, NIP-taurine inhibits irreversibly, indicating that it may be a useful label for its binding site. When present at the outside of the cell, NIP-taurine binds with low affinity to a site that seems to be the Cl- transport site (on the basis of its affinity for Cl-) and with much higher affinity to a different site, MN, which has a much lower affinity for Cl-. In this respect, NIP-taurine resembles NAP-taurine, and an analysis of interactions between these two probes is consistent with the idea that they bind to the same two sites. The affinity of NIP-taurine for the high-affinity MN site is enhanced by about fourfold when the transport protein, band 3, is in the conformation with the transport site facing outward (Eo), as compared with the conformation with the transport site facing inward (Ei). External Cl-, but not cytoplasmic Cl-, competes with NIP-taurine for binding to the external, high affinity site. Thus NIP-taurine provides a label for an external site, at which Cl- and perhaps other anions bind, which is separate from both the transport site and the cytoplasmic modifier site at which high Cl- concentrations inhibit Cl- exchange.

Adult↗

Taurine behaves as an osmolyte in Madin-Darby canine kidney cells. Protection by polarized, regulated transport of taurine.

Using a clonal growth assay, we demonstrated that taurine, a nonperturbing osmolyte accumulated in kidney medulla, brain, and some other tissues of hypertonic experimental animals can function as a nonperturbing osmolyte in Madin-Darby canine kidney (MDCK) cells. The taurine content of hypertonic MDCK cells is twice that of isotonic MDCK cells (isotonic 160 nmol/mg protein; hypertonic 320 nmol/mg protein). Therefore we studied taurine transport in MDCK cells grown on porous supports and then studied the effect of hypertonicity which is known to elicit increased uptake of some other nonperturbing osmolytes by MDCK cells. Basal uptake exceeded apical uptake, with Km and Vmax of 56 microM and 933 pmol/min.mg protein on the basal surface and 10 microM and 50 pmol/min.mg protein on the apical surface. On both surfaces, virtually all taurine uptake was Na+ and Cl- dependent. 24 h after cells were shifted to hypertonic medium (500 mosmol/kg), taurine uptake doubled on the basolateral surface without change on the apical surface. The response to hypertonicity was the result of an increase in Vmax without change in Km. There was no change in taurine efflux when cells were shifted from isotonic to hypertonic medium. When cells adapted to hypertonic medium were shifted to isotonic medium, a large transient basolateral efflux of taurine occurred within 10 min. We conclude that taurine can function as a nonperturbing osmolyte in MDCK cells and that tonicity-regulated taurine transport is a basolateral function in MDCK cells.

Animals↗

Rigid analogs of taurine as potential taurine antagonists.

In this study we tested the potential taurine-antagonistic properties of three rigid analogs of taurine, 3-amino- (1), 3-hydrazino- (2) and 3-aminomethyl-1,2,4-benzothiadiazine-1,1-dioxide (3), which were prepared in our laboratory, using TAG (6-aminomethyl-3-methyl-1,2,4-benzothiadiazine-1,1- dioxide) (4), the only antagonist of taurine so far available, as reference compound in "in vivo" and "in vitro" experiments. Some physicochemical properties of (1), (2) and (3) were studied and the synthesis of TAG (4) was improved with a new preparative method. A dose-effect study performed by injecting intracerebroventricularly (1), (2) and (3) showed that these compounds have none of exciting effects exerted by the high doses of TAG (4). (1) and (3) as well as TAG (4), were found to antagonize the controlateral turning induced by the intracerebro injection of taurine and to potentiate the sedative effect of diazepam. We failed to find specific binding for taurine in different brain synaptic membrane preparations using 3H-taurine as radioligand and taurine, (1) and (3) as binding displacer. (1), (3) and TAG (4) however were found to antagonize the inhibitory effect of taurine on 3H-diazepam binding. These results seem to indicative that at least (1) and (3), which were more extensively studied than (2) because of their better solubility, are taurine antagonists with an apparent better selectivity than TAG (4).

Animals↗

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

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.

Animals↗

Taurine-supplemented total parenteral nutrition and taurine status of malnourished cancer patients.

The status of plasma taurine and whether its concentration can be influenced by total parenteral nutrition (TPN) was determined in 51 malnourished fasting cancer patients after surgery and 7-14 days after starting TPN providing 41 +/- 2 kcal, 0.30 +/- 0.02 g N kg-1.day-1 and 40 mg pyridoxine. Plasma taurine was 50% lower in patients than in control subjects. Plasma taurine was significantly greater than baseline only after 14 days of TPN. We also studied the effects of surgery and taurine supplementation (8.6 mg.kg-1.day-1) on plasma and urine taurine concentrations in 12 malnourished patients. Preoperatively, all patients had normal plasma taurine concentrations; postoperatively, it was in the deficient range in 4 patients. Taurine-supplemented patients initially had higher than baseline concentrations; by day 10, none had subnormal levels. Subnormal taurine concentrations commonly occur in malnourished postoperative cancer patients; surgery further precipitates their fall. Plasma concentrations were maintained only with taurine-supplemented TPN.

Adult↗