The cytoprotective role of taurine in exercise-induced muscle injury

Summary.  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. Received October 22, 2001 Accepted February 1, 2002     

The taurine transporter gene and its role in renal development

Summary. This paper examines a unique hypothesis regarding an important role for taurine in renal development. Taurine-deficient neonatal kittens show renal developmental abnormalities, one of several lines of support for this speculation. Adaptive regulation of the taurine transporter gene is critical in mammalian species because maintenance of adequate tissue levels of taurine is essential to the normal development of the retina and the central nervous system. Observations of the remarkable phenotypic similarity that exists between children with deletion of bands p25-pter of chromosome 3 and taurine-deficient kits led us to hypothesize that deletion of the renal taurine transporter gene (TauT) might contribute to some features of the 3p-syndrome. Further, the renal taurine transporter gene is down-regulated by the tumor suppressor gene p53, and up-regulated by the Wilms tumor (WT-1) and early growth response-1 (EGR-1) genes. It has been demonstrated using WT-1 gene knockout mice that WT-1 is critical for normal renal development. In contrast, transgenic mice overexpressing the p53 gene have renal development defects, including hypoplasia similar to that observed in the taurine-deficient kitten. This paper reviews evidence that altered expression of the renal taurine transporter may result in reduced intracellular taurine content, which in turn may lead to abnormal cell volume regulation, cell death and, ultimately, defective renal development. Received January 25, 2000/Accepted January 31, 2000     

A study on the estimation of sulfur-containing amino acid metabolism by the determination of urinary sulfate and taurine

Summary.  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. Received December 3, 2001 Accepted January 2, 2002 Published online August 30, 2002 Authors' address: Dr. Toshihiko Ubuka, Department of Clinical Nutrition, Kawasaki University of Medical Welfare, Kurashiki Okayama, 701-0193 Japan, E-mail: ubukatos@mw.kawasaki-m.ac.jp     

Co-variation of plasma sodium,taurine and other amino acid levels in critical illness

Summary.  This study investigates the relationship between changes in plasma sodium and changes in amino acid levels in a patient with post-traumatic sepsis and prolonged critical illness. Ninety-two consecutive measurements were performed at regular intervals over a period of many weeks; these consisted in the determination of full amino-acidograms, plasma sodium and complementary variables. A unique, highly significant inverse correlation between taurine and plasma sodium was found (r² = 0.48, p < 0.001). All other amino acids were unrelated, or much more weakly related, to sodium. Taurine was also strongly and directly related to phosphoethanolamine, glutamate and aspartate. Changes in sodium and in levels of these amino acids explained up to 86% of the variability of taurine. Besides, levels of these amino acids maintained a high degree of co-variation, remaining reciprocally related one to each other, directly, with r² ranging between 0.33 and 0.59 (p < 0.001 for all). There were similar findings for β-alanine, which however was measured inconsistently. These data provide gross clinical evidence of a specific link binding plasma sodium and taurine levels, and may be consistent with occurrence of opposite and interdependent shifts of sodium and taurine between intravascular and extravascular space, to maintain osmoregulation. Co-variation of taurine with the other amino acids may be related to the same phenomenon, and/or to similarities in transport systems and chemical structure, or true metabolic interactions. Received April 16, 2002 Accepted June 19, 2002 Published online November 14, 2002 RID="*" ID="*"  Presented at the 7^th International Congress on Amino Acids and Proteins, Vienna (Austria), August 6–10, 2001. Acknowledgements The authors acknowledge the kind assistance of Mr. Maurizio Cianfanelli, from the Catholic University School of Medicine, Rome, Italy. Authors' address: Dr. Carlo Chiarla, Via Augusto Tebaldi, 19, I-00168 Roma, Italy, E-mail: carlo.chiarla@rm.unicatt.it     

The use of taurine analogues to investigate taurine functions and their potential therapeutic applications

Summary.  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. Received January 2, 2002 Accepted January 28, 2002 Published online August 30, 2002 Acknowledgements This research has been funded by the COST Chemistry programmes COST D8 “Chemistry of Metals in Medicine” and D-13 “New Molecules for Human Health Care”. All of the authors are members of the Working Group D13/0011/00 “Investigation of mechanisms underlying the pharmacological actions of taurine upon cell apoptosis and calcium homeostasis”. Authors' address: Dr. R.J. Ward, Unite de Biochimie, Catholic Universite de Louvain, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium, E-mail: ward@bioc.ucl.ac.be     

Relationship of taurine and other amino acids in plasma and in neutrophils of septic trauma patients

Summary. Recently, an interdependency of plasma taurine and other amino acids as well as metabolic and clinical variables implicating therapeutic options was reported. This result may be an indication that plasma taurine levels are directly related to intracellular levels. Therefore, the aim of this study was to analyse the possible relationship between taurine levels in plasma and in neutrophils, the relationship to other amino acids, and variables quantifying metabolic impairment and severity of sepsis in multiple trauma patients developing sepsis. After multiple trauma taurine decreased significantly in plasma in thirty-two patients as well as within the neutrophil and does not recover in sepsis. Lower individual levels in the neutrophil did not follow lower individual levels in plasma and no correlation of taurine in plasma and in the neutrophils could be observed. In sepsis, only plasma showed an interdependency of taurine, aspartate, and glutamate. No association between taurine plasma or intracellular levels and SOFA score as indicator for severity of sepsis or metabolic variables was observed. After multiple trauma and in sepsis, taurine uptake in cells (which is regulated in different ways), and intracellular taurine (which serves e.g. as an osmolyte) can be influenced. Therefore a prediction of the neutrophil taurine pool seems not fully possible from taurine plasma levels. Intracellular taurine has some unique properties explaining the missing interdependency despite some similarities in osmoregulation and metabolic interactions to other amino acids. The association of taurine, aspartate, and glutamate in plasma cannot be simply transferred to the neutrophils intracellular level. The clinical meaning of the plasma correlation remains unclear. A dependency of plasma and neutrophil taurine to severity of sepsis and to metabolic variables seems not possible because of the multifactorial pathophysiology of sepsis.     

The effect of taurine on renal ischemia/reperfusion injury

Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.     

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

Summary. 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. Received January 25, 2000/Accepted January 31, 2000     

Effects ofin vivo taurine depletion on induced- chemiluminescence production in macrophages isolated from rat lungs

Summary Alveolar macrophages isolated by pulmonary lavage from partially taurine-depleted ratsdemonstrated increased (2–2.6 fold) chemiluminescence due to the extracellular reaction between exogenous zymosan and various reactive forms of oxygen compared to macrophages isolated from control animals. Partial taurine depletion was achieved by adding 3% ß-alanine to the drinking water of the rats for 5 weeks prior to harvesting the macrophages. Superoxide dismutase activity was not increased in the lung tissue of the taurine-depleted rats. These data suggest that taurine has antioxidant properties and that taurine depletion is potentially deleterious to alveolar macrophages and pulmonary tissue.     

A taurine and caffeine-containing drink stimulates cognitive performance and well-being

Summary. Caffeine- and taurine-containing drinks have been on the European market for about a decade, and research on the individual constituents of these drinks indicates an improvement in cognitive performance resulting from consumption of such drinks. In this double-blind, placebo-controlled study using 10 graduate students, we obtained the P300 components of event-related potential (ERP) waveforms following an auditory oddball paradigm, measured motor reaction time, and applied the d2 test for the assessment of attention. Status of mood was assessed by the “Basler-Befindlichkeitsbogen” questionnaire, a standard test for evaluation of feelings of well-being. Measurements were made at night, prior to and starting one hour after consumption of energy drink ingredients or placebo. At the end of the experiment (midnight), P300 latency and motor reaction time were significantly longer compared with baseline measurements in the placebo group, but were unchanged in the energy drink group. In the test system for evaluating feelings of well-being, total scores, vitality scores and social extrovertedness scores were significantly decreased in the placebo group but not in the energy drink group. The findings clearly indicate that the mixture of three key ingredients of Red Bull^R Energy Drink used in the study (caffeine, taurine, glucuronolactone) have positive effects upon human mental performance and mood. These effects may be mediated by the action of caffeine on purinergic (adenosinergic) receptors and taurine modulation of receptors. As half of the study cohort were non-caffeine users, the described effects cannot be explained in terms of the restoration of plasma caffeine levels to normal following caffeine withdrawal. Received January 5, 2000/Accepted June 5, 2000     

Effects of chronic taurine treatment on reactivity of the rat aorta

Summary. The effects of chronic taurine treatment on the reactivity of the aorta form male Wistar-Kyoto rats were investigated. Contractile responses to norepinephrine (NE) and potassium chloride (KCl) were attenuated in aortic rings from taurine-treated rats as compared to controls both in the absence and presence of endothelium. However, the degree of attenuation was greater in endothelium-intact tissues contracted with NE. Acetylcholine (Ach)-induced relaxation responses were augmented in endothelium-intact vessels from rats supplemented with taurine compared to the responses observed in control preparations. Relaxation responses of the aortae from control and taurine-treated rats to sodium nitroprusside (SNP) were not different from each other. Our results suggest that taurine treatment attenuates vascular contractility nonspecifically and this effect is partly mediated via the endothelium. Received December 20, 1999/Accepted January 9, 2000     

The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage--a light and electron microscopic study

Summary.  The results regarding taurine pretreatment on CCl₄-induced hepatic injury are controversial. To assess the therapeutic efficacy of taurine on rat liver injury, hepatic malondialdehyde, glutathione, and hydroxyproline levels together with morphologic alterations in the liver following CCl₄ administration were investigated. The rats were divided into three groups. Taurine-treated animals received 15 ml/kg/day of a 5% taurine solution by a gastric tube for 5 days before administering CCl₄ (2 ml/kg, intraperitoneally, in a single dose). CCl₄-treated rats received the same amount of saline solution. Control animals received no treatment. The increase of hepatic malondialdehyde formation in the CCl₄-treated group was partially prevented by taurine pretreatment, but taurine had no significant effect on the glutathione and hydroxyproline content in the CCl₄-treated rats. Taurine pretreatment induced a marked beneficial effect regarding the prevention of hepatocellular necrosis and atrophy as demonstrated morphologically. In conclusion, these results suggest that taurine pretreatment might not significantly change the biochemical parameters, but prevents the morphologic damage caused by CCl₄ in the early stages. Received March 17, 2001 Accepted July 18, 2001     

Effects of taurine on polymorphonuclear phagocytosis activity in burned patients

Summary.  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. Received December 17, 2001 Accepted January 17, 2002 Published online August 30, 2002 Authors' address: Dr. Mireia Farriol, Centre d'Investigacions Bioquímicas i Biología Molecular (CIBBIM), Hospital General Vall d'Hebron Passeig Vall d'Hebron 119-129, E-08035 Barcelona, Spain, Fax: 34-93-2746831, E-mail: farriol@hg.vhebron.es     

Role of osmoregulation in the actions of taurine

Summary. Taurine regulates an unusual number of biological phenomena, including heart rhythm, contractile function, blood pressure, platelet aggregation, neuronal excitability, body temperature, learning, motor behavior, food consumption, eye sight, sperm motility, cell proliferation and viability, energy metabolism and bile acid synthesis. Many of these actions are associated with alterations in either ion transport or protein phosphorylation. Although the effects on ion transport have been attributed to changes in membrane structure, they could be equally affected by a change in the activity of the affected transporters. Three common ways of altering transporter activity is enhanced expression, changes in the phosphorylation status of the protein and cytoskeletal changes. Interestingly, all three events are altered by osmotic stress. Since taurine is a key organic osmolyte in most cells, the possibility that the effects of taurine on ion transport could be related to its osmoregulatory activity was considered. This was accomplished by comparing the effects of taurine, cell swelling and cell shrinkage on the activities of key ion channels and ion transporters. The review also compares the phosphorylation cascades initiated by osmotic stress with some of the phosphorylation events triggered by taurine depletion or treatment. The data reveal that certain actions of taurine are probably caused by the activation of osmotic-linked signaling pathways. Nonetheless, some of the actions of taurine are unique and appear to be correlated with its membrane modulating and phosphorylation regulating activities. Received January 25, 2000/Accepted January 31, 2000     

Synthesis of N-quinonyltaurines

Summary.  Both 1,4-benzoquinones and 1,4-naphthoquinones were attached to the non-proteinogenic amino acid taurine to form N-quinonyl taurine derivatives. The products were formed via the direct Michael-like addition or by substitution of a good leaving group. An attempt to bridge the two moieties via an ureido spacer resulted in the formation of a bis-quinonylamino isocyanurate derivative. Preliminary MO calculations provided internal ground-state geometries and orbital coefficients of the HOMO levels in two representing taurine conjugates. Received May 6, 2002 Accepted August 13, 2002 Published online December 18, 2002 Acknowledgments This research was supported by the Israel Science Foundation founded by the Academy of Science and Humanities. We wish to thank Ms. Ethel Solomon for skilled technical help. Authors' address: Prof. Shmuel Bittner, Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel, Fax: (972)-8-6472943, E-mail: bittner@bgumail.bgu.ac.il     

Effect of ischemia,calcium depletion and repletion,acidosis and hypoxia on cellular taurine content

Summary.  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. Received November 15, 2001 Accepted January 15, 2002 Published online October 3, 2002 Acknowledgements This study was supported with a grant from the Taisho Pharmaceutical Company. Authors' address: Dr. Stephen W. Schaffer, Department of Pharmacology, University of South Alabama, School of Medicine, Mobile, Alabama, U.S.A., E-mail: sschaffe@jaguarl.usouthal.edu     

Production of hypotaurine, taurine and sulfate in rats and mice injected with L-cysteinesulfinate

Summary. We studied in vivo production of taurine, hypotaurine and sulfate following subcutaneous administration of L-cysteinesulfinate (CSA) to rats and mice. When 5.0 mmol/kg of body weight of CSA was injected to rats, increased urinary excretions of taurine, hypotaurine and sulfate in 24 h urine were 617, 52 and 1,767 μmol/kg, respectively. From these results together with our previous data, sulfate production was calculated to be 1.6 times greater than taurine production. Increased contents (μmol/g of wet tissue) over the control of taurine and hypotaurine in mouse tissues at 60 min after the injection of 5.0 mmol/kg body weight of CSA were: liver, 3.5 and 9.9; kidney, 0.3 and 5.2; heart, 3.7 and 0.2; blood plasma, 0.4 and 0.2, respectively. Upon loading of hypotaurine or taurine, tissue contents of these amino acids in liver and kidney increased greatly. Our results indicate that liver is the most active tissue for taurine production, followed by kidney, and that external CSA, hypotaurine and taurine are easily taken up by these tissues.     

Stabilization of calcium uptake in rat rod outer segments by taurine and ATP

Summary. Calcium ion (Ca²⁺) uptake was measured in rod outer segments (ROS) isolated from rat retina in the presence of varying concentrations of CaCl₂ in the incubation buffer (1.0–2.5 mM). It is known that taurine increases Ca²⁺ uptake in rat ROS in the presence of ATP and at low concentrations of CaCl₂ (Lombardini, 1985a); taurine produces no significant effects when CaCl₂ concentrations are increased to 1.0 and 2.5 mM. With the removal of both taurine and ATP, Ca²⁺ uptake in rat ROS increased significantly in the presence of 2.5 mM CaCl₂. Taurine treatment in the absence of ATP was effective in decreasing Ca²⁺ uptake at the higher levels of CaCl₂ (2.0 and 2.5 mM). Similar effects were observed with ATP treatment. The data suggest that taurine and ATP, alone or in combination, limit the capacity of the rat ROS to take up Ca²⁺ to the extent that a stable uptake level is achieved under conditions of increasing extracellular Ca²⁺, indicating a protective role for both agents against calcium toxicity. Received January 25, 2000/Accepted January 31, 2000     

Kinetics of taurine depletion and repletion in plasma, serum, whole blood and skeletal muscle in cats

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.     

Downregulation of taurine uptake in multidrug resistant Ehrlich ascites tumor cells

Summary.  In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal rate constant for the initial taurine uptake was reduced by 45% (high-affinity system) and 49% (low affinity system) in the resistant subline whereas the affinity of the transporters to taurine was unchanged. By immunoblotting we identified 3 TauT protein bands in the 50–70 kDa region. A visible reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1 gene product P-glycoprotein (P-gp). Using 5 progressively DNR resistant Ehrlich cell sublines with different P-gp expression pattern no correlation between taurine uptake and P-gp expression was found. Taurine uptake in MDR1 transfected NIH/3T3 mouse fibroblasts was in contrast to the findings in Ehrlich cells increased compared to the parental fibroblasts. It is concluded that the reduced taurine uptake in resistant Ehrlich cells reflects a down regulation of the taurine transporter at the mRNA and protein level and it is most probably not related to P-gp overexpression. Received October 22, 2001 Accepted November 26, 2001