Taurine Depletion Research Articles

The effect of taurine depletion by beta-alanine treatment on the susceptibility to ethanol-induced hepatic dysfunction in rats.

Alcohol was administered chronically to female Sprague-Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in significant hepatic steatosis and lipid peroxidation. Beta-alanine, when co-administered with alcohol, seemed to increase hepatic steatosis, as assessed histologically, but decreased triglyceride levels as measured biochemically. In addition, beta-alanine and especially alcohol co-administered with beta-alanine, significantly increased homocysteine and cysteine excretion into urine throughout the 28-day period of ethanol administration. Serum homocysteine levels were significantly higher in alcohol- and alcohol plus beta-alanine-treated animals compared to pair-fed control animals. Alcohol did not affect the urinary excretion of taurine, except after 21 days, when levels were reduced. Levels of liver taurine were markedly depleted in animals receiving alcohol and particularly alcohol plus beta-alanine, compared to pair-fed controls. Liver and serum taurine levels were also markedly depleted in animals receiving beta-alanine and alcohol plus beta-alanine, compared to non-beta-alanine-treated animals. There was evidence of slight cholestasis in animals treated with alcohol and more so with alcohol plus beta-alanine, as indicated by raised serum alkaline phosphatase and bile acids. These in vivo findings demonstrate for the first time that animals treated with beta-alanine may be more susceptible to ethanol-induced hepatic dysfunction, possibly as a result of taurine depletion.

Role of osmoregulation in the actions of taurine.

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.

Cardiovascular responses of the taurine-depleted rat to vasoactive agents.

The objective of this study was to assess the effect of taurine-depletion on cardiovascular responses of rat to vasoactive agents. Male Wistar-Kyoto (WKY) rats were given either tap water (control) or 3% beta-alanine (taurine-depleted) for three weeks. Thereafter, mean arterial pressure (MAP) and heart rate of the freely moving animal were measured in response to vasoactive agents. Administration of phenylephine (5-40 microg/kg/min; i.v.) resulted in a similar and significant increase in MAP but a reduction in heart rate in both control and taurine-depleted groups. On the other hand, administration of sodium nitroprusside (15-300 microg/kg/min; i.v.) elicited a similar and significant reduction in MAP but increased heart rate in both groups. Lack of a differential response to phenylephrine and sodium nitroprusside between the two groups suggests that baroreflex regulation of cardiovascular function is not adversely affected by taurine-depletion. Administration of angiotensin II (0.1-3.0 microg/kg/min; i.v.) resulted in a dose-related increase in the pressor response and a decrease in heart rate in both groups. However, angiotensin II-induced pressor response was reduced in the taurine-depleted compared to the control rats (p < 0.05); heart rate was similarly reduced in both groups. Acute exposure to beta-alanine (3 g/kg; i.v., 30-minutes) did not alter angiotensin II-induced hemodynamic responses. Similarly, incubation of aortic rings with beta-alanine (40mM, 30 minutes) did not affect the contractile responses to angiotensin II. The results suggest that beta-alanine, per se, does not affect angiotensin II-induced responses in rat. However, beta-alanine-induced taurine depletion is associated with a reduction in the pressor response to angiotensin II without impairing baroreflex function.

Hypoxia Is Not A Cause Of Oxidative Stress In Diabetic Peripheral Nerve

Severe ischemia and hypoxia in the neural tissues are associated with free radical production. The purpose of our study was to explore the contribution of endoneurial hypoxia vs hyperglycemia to oxidative stress in early experimental diabetic neuropathy. This was achieved by evaluating α1‐adrenoceptor antagonist prazosin (5 mg/kg in the drinking water, for 3 wks from induction of diabetes), on diabetes‐induced changes in endoneurial vascular conductance (VC), biochemical markers of nerve hypoxia, lipid peroxidation and antioxidative defense. Diabetes‐induced decrease in VC as well as free NAD+/NADH ratios in mitochondrial cristae, matrix and cytosol, were completely (VC, free NAD+/NADH in mitochondrial matrix) or partially prevented by prazosin. Accumulation of lipid peroxidation products, depletion of GSH, ascorbate and taurine, increase in GSSG/GSH and DHAA/AA ratios were not affected by vasodilator therapy. Antioxidative defense enzyme activities were similar in control and diabetic rats treated with/without prazosin. Blood and nerve glucose concentrations were similarly elevated in prazosin‐treated and untreated diabetic rats. In conclusion, hyperglycemia, but not hypoxia, is a major cause of oxidative stress in diabetic peripheral nerve. Free radical production in PNS is dependent on the degree of hypoxia, and is not initiated by relatively mild hypoxia in early diabetes.

Taurine Replacement Prevents Apoptosis In Experimental Diabetic Neuropathy

The pathophysiology of diabetic neuropathy (DN) is complex involving both metabolic and vascular deficits. Recent data have implicated a potential role for programmed cell death (PCD) in the development of experimental DN (EDN). Oxidative stress has emerged as a leading candidate in the development of nerve blood flow (NBF) and nerve conduction deficits. We have previously shown that replacement of the endogenous antioxidant taurine in the nerve of streptozotocin‐diabetic (STZ‐D) rats corrects neuro‐vascular dysfunction, prevents deficits in Na,K‐ATPase activity and attenuates motor and sensory NCV slowing. The aims of this study were to examine the hypothesis that oxidative stress‐mediated mitochondrial dysfunction may promote the activation of PCD pathways in STZ‐D rats and to determine whether these effects could be attenuated by taurine. Dorsal root ganglion (DRG) neurons were extracted from perfused control (C), STZ‐D and STZ‐D rats given a 1% taurine supplemented diet for 6 weeks. STZ‐D induced a significant decrease in sensory nerve conduction velocity (SNCV) and NBF vs controls and these deficits were corrected by taurine. Lumbar and sacral DRG were sectioned at 10 mm intervals and slides were prepared from two different sampling sites. Apoptosis was detected by TUNEL staining. 150 or more DRG nuclei were counted per animal. In STZ‐D rats 21.3 ± 4.9% of DRG nuclei were found to be TUNEL positive as compared with 2.9 ± 2.1% in controls (p &lt; 0.05). Taurine replacement markedly attenuated apoptosis since only 6.5 ± 2.9% neurons were TUNEL positive. In summary, 6 weeks of STZ‐D increased apoptosis in DRG neurons of STZ‐D rats. This increase in apoptosis could be prevented by replacement of the endogenous antioxidant taurine, implicating a role of taurine depletion in the development of sensory neuron degeneration.

Evaluation of alpha(1)-adrenoceptor antagonist on diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense.

The role for nerve blood flow (NBF) vs. other factors in motor nerve conduction (MNC) slowing in short-term diabetes was assessed by evaluating alpha(1)-adrenoceptor antagonist prazosin on NBF, MNC, as well as metabolic imbalances and oxidative stress in the neural tissue. Control and diabetic rats were treated with or without prazosin (5 mg.kg(-1).d(-1) for 3 wk). NBF was measured by hydrogen clearance. Both endoneurial vascular conductance and MNC velocity were decreased in diabetic rats vs. controls, and this decrease was prevented by prazosin. Free NAD(+):NADH ratios in mitochondrial cristae, matrix, and cytosol assessed by metabolite indicator method, as well as phosphocreatine levels and phosphocreatine/creatine ratios, were decreased in diabetic rats, and this reduction was ameliorated by prazosin. Neither diabetes-induced accumulation of two major glycation agents, glucose and fructose, as well as sorbitol and total malondialdehyde plus 4-hydroxyalkenals nor depletion of myo-inositol, GSH, and taurine or decrease in (Na/K)-ATP-ase activity were affected by prazosin. In conclusion, decreased NBF, but not metabolic imbalances or oxidative stress in the neural tissue, is a key mechanism of MNC slowing in short-term diabetes. Further experiments are needed to estimate whether preservation of NBF is sufficient for prevention of nerve dysfunction and morphological abnormalities in long-standing diabetes or whether the aforementioned metabolic imbalances closely associated with impaired neurotropism are of greater importance in advanced than in early diabetic neuropathy.

Evaluation of α1‐adrenoceptor antagonist on diabetes‐induced changes in peripheral nerve function, metabolism, and antioxidative defense

The role for nerve blood flow (NBF) vs. other factors in motor nerve conduction (MNC) slowing in short-term diabetes was assessed by evaluating α1-adrenoceptor antagonist prazosin on NBF, MNC, as well as metabolic imbalances and oxidative stress in the neural tissue. Control and diabetic rats were treated with or without prazosin (5 mg·kg−1·d−1 for 3 wk). NBF was measured by hydrogen clearance. Both endoneurial vascular conductance and MNC velocity were decreased in diabetic rats vs. controls, and this decrease was prevented by prazosin. Free NAD+:NADH ratios in mitochondrial cristae, matrix, and cytosol assessed by metabolite indicator method, as well as phosphocreatine levels and phosphocreatine/creatine ratios, were decreased in diabetic rats, and this reduction was ameliorated by prazosin. Neither diabetes-induced accumulation of two major glycation agents, glucose and fructose, as well as sorbitol and total malondialdehyde plus 4-hydroxyalkenals nor depletion of myo-inositol, GSH, and taurine or decr...

Interaction between the actions of taurine and angiotensin II.

The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion of taurine has been linked to developmental defects, retinal damage, immunodeficiency, impaired cellular growth and the development of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy promoting drinks. Nonetheless, the use of taurine as a drug to treat specific diseases has been limited. One disease that responds favorably to taurine therapy is congestive heart failure. In this review, we discuss three mechanisms that might underlie the beneficial effect of taurine in heart failure. First, taurine promotes natriuresis and diuresis, presumably through its osmoregulatory activity in the kidney, its modulation of atrial natriuretic factor secretion and its putative regulation of vasopressin release. However, it remains to be determined whether taurine treatment promotes salt and water excretion in humans with heart failure. Second, taurine mediates a modest positive inotropic effect by regulating [Na+]i and Na+/Ca2+ exchanger flux. Although this effect of taurine has not been examined in human tissue, it is significant that it bypasses the major calcium transport defects found in the failing human heart. Third, taurine attenuates the actions of angiotensin II on Ca2+ transport, protein synthesis and angiotensin II signaling. Through this mechanism taurine would be expected to minimize many of the adverse actions of angiotensin II, including the induction of cardiac hypertrophy, volume overload and myocardial remodeling. Since the ACE inhibitors are the mainstay in the treatment of congestive heart failure, this action of taurine is probably very important.

Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor.

Taurine is a sulphonic aminoacid present in high amounts in various tissues including cardiac and skeletal muscles showing different properties such as antioxidative, antimyotonic and anti-schaemic effects. The cellular mechanism of action of taurine is under investigation and appears to involve the interaction of the sulphonic aminoacid with several ion channels. Using the patch-clamp technique we studied the effects of taurine in rat skeletal muscle fibres on ATP-sensitive K(+) channel (K(ATP)) immediately after excision and on channels that underwent rundown. The cytoplasmic application of 20 mM of taurine reduced the K(ATP) current; this effect was reverted by washout of the drug solution. In this experimental condition the IC(50) was 20.1 mM. After rundown, taurine inhibited the K(ATP) current with similar efficacy. Competition experiments showed that taurine shifted the dose-response inhibition curve of glybenclamide to the left on the log-dose axis without significantly affecting those of ATP or Ca(2+) ion. Single channel recording revealed that taurine affects the close state of the channel prolonging it and reducing the bursts duration. Our data indicate that taurine inhibits the muscular K(ATP) channel interfering with the glybenclamide site on the sulphonylurea receptor of the channel or on the site allosterically coupled to it. During ischaemia and hypoxia, the skeletal and heart muscles undergo several changes; for example, the activation of K(ATP) channels and loss of the intracellular taurine content. The depletion of taurine during ischaemia would contribute to the early activation of K(ATP) channels and salvage the intracellular ATP content.

TAURINE ATTENUATES COLD ISCHEMIA-REOXYGENATION INJURY IN RAT LIVER1

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

Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy.

Experimental diabetic peripheral neuropathy (DPN) is marked by impaired nerve conduction velocity (NCV), reduced nerve blood flow (NBF), and a variety of metabolic abnormalities in peripheral nerve that have been variously ascribed to hyperglycemia, abnormal fatty acid metabolism, ischemic hypoxia, and/or oxidative stress. Some investigators propose that NCV slowing in experimental DPN can be explained entirely on the basis of nerve energy depletion secondary to reduced NBF. This article reports highly selective effects of administration of the antioxidant DL-alpha-lipoic acid (LA) to streptozotocin-injected diabetic rats. LA improved digital sensory but not sciatic-tibial motor NCV, corrected endoneurial nutritive but not composite NBF, increased the mitochondrial oxidative state without correcting nerve energy depletion, and enhanced the accumulation of polyol pathway intermediates without worsening myo-inositol or taurine depletion. These studies implicate oxidative stress as an important pathophysiological factor in experimental DPN. They reveal complex interrelationships among nerve perfusion, energy metabolism, osmolyte content, conduction velocity, and oxidative stress that may reflect the heterogeneous and compartmentalized composition of peripheral nerve.

Plasma taurine levels in broilers with pulmonary hypertension syndrome induced by unilateral pulmonary artery occlusion

Low plasma levels of taurine are associated with losses of cardiac sarcomeric proteins, leading to heart failure in mammals. Recently, it was proposed that cardiac taurine depletion serves to defend the heart against injury caused by regional ischemia in mammals. The role of taurine has not been well documented in broilers, particularly in relation to pulmonary hypertension syndrome (PHS; ascites). Three independent experiments evaluated plasma taurine in male broilers by utilizing the following treatments: unoperated controls (CONTROL; n = 10 in each experiment); sham operated (SHAM; n = 11, 12, and 10); or, unilaterally pulmonary artery clamped (PAC; n = 18, 29, and 24) that did (PAC-ascites) or did not (PAC-normal) develop ascites within 12 d postsurgery. Plasma samples were collected 9 and 11 d postsurgery in Experiments 1 and 2, respectively, and 2 d before and 4, 8, and 12 d after surgery in Experiment 3. Plasma taurine was analyzed by HPLC. Twelve days postsurgery, the birds were euthanatized, and ventricles were weighed for calculating the right:total ventricular weight ratio (RV:TV). The RV:TV of PAC birds (>0.35) consistently was higher (P < 0.01) than that of CONTROL and SHAM birds (<0.27 and 0.25, respectively). In Experiments 1 and 2, plasma taurine was higher (P < 0.05) in PAC-ascites (380 and 370 nmol/mL) than in SHAM broilers (183 and 186 nmol/mL), whereas CONTROL (262 and 278 nmol/mL) and PAC-normal (362 and 300 nmol/mL) broilers tended to have intermediate plasma taurine levels. In Experiment 3, PAC birds had higher (P < 0.05) plasma taurine at 8 and 12 d postsurgery when compared with presurgery levels, whereas plasma taurine was unchanged over time in CONTROL and SHAM birds. These results suggest cardiac taurine may be released into the plasma as a protective mechanism in response to the induction of pulmonary hypertension, hypoxemia, and right-side heart failure, similar to the mechanism reported for protecting cardiac muscle from ischemia in mammals.

Downregulation of the human taurine transporter by glucose in cultured retinal pigment epithelial cells.

In diabetes, activation of the aldose reductase (AR) pathway and alterations of glucose-sensitive signal transduction pathways have been implicated in depletion of intracellular taurine, an endogenous antioxidant and compatible osmolyte. Cellular taurine accumulation occurs by an osmotically induced, protein kinase C (PKC)-regulated Na(+)-taurine cotransporter (hTT). The effects of ambient glucose on taurine content, hTT activity, and hTT gene expression were therefore evaluated in low and high AR-expressing human retinal pigment epithelial cell lines. In low AR-expressing cells, 20 mM glucose decreased taurine content, hTT transporter activity, and mRNA levels, and these effects were unaffected by AR inhibition (ARI). In these cells, the inhibitory effects of high glucose on hTT appeared to be posttranscriptionally mediated, because 20 mM glucose decreased hTT mRNA stability without affecting hTT transcriptional rate. Inhibition of PKC overcame the decrease in hTT activity in high glucose-exposed cells. In high AR-expressing cells, prolonged exposure to 20 mM glucose resulted in intracellular taurine depletion, which paralleled sorbitol accumulation and was prevented by ARI. In these cells exposed to 5 mM glucose, hTT mRNA abundance was decreased and declined further in 20 mM glucose but was corrected by ARI. In 5 mM glucose, hTT transcriptional rate was markedly decreased in high AR-expressing cells, did not decline further in 20 mM glucose, but was increased by ARI to levels above those observed in low AR-expressing cells. Therefore, glucose rapidly and specifically decreases taurine content, hTT activity, and mRNA abundance by AR-unrelated and AR-related posttranscriptional and transcriptional mechanisms.

Profiles of serum proteins and free amino acids associated with chloroquine retinopathy.

The effects of chronic chloroquine administration on serum proteins and free amino acids of rabbits and the accompanying ultrastructural changes in the retina were investigated. Thirty pigmented rabbits were injected intramuscularly with chloroquine diphosphate (14 mg/Kg bw). Fifteen rabbits served as control. Blood samples drawn after 1, 2, 3, 4, 5, 6 and 12 months were assayed for serum proteins by Bio-analytic kits and horizontal electrophoretic technique. Free amino acids were determined by Beckman analyzer. Central retinal tissue was fixed in 4% glutaraldehyde, embedded in araldite CY212 and sectioned for ultrastructural examination. Histopathologic changes were apparent within three months, initially affecting the pigment epithelium and photoreceptors and later involving the remaining neuroretinal layers. Hypoproteinemia gradually developed mainly due to a sharp drop in albumin and alpha 1 and 2 globulin fractions, inspite of an increase in beta and gamma globulin fractions. The concentration of non-essential amino acids varied considerably from a depletion of taurine, aspartine, glutamine, tryptophan and arginine to an increase of serine, alanine, GABA and ornithine. The most outstanding effect was the disappearance of tyrosine and its return to normal value at the end of the experiment. The disturbances in protein pattern and free amino acid levels are an indication of chloroquine toxicity and may be implicated in the retinopathy.

Taurine Status in Cats Is Not Maintained by Dietary Cysteinesulfinic Acid ,

Endogenous synthesis of taurine by cats is limited. Putative precursors of taurine, cysteinesulfinic acid and cysteic acid, were fed to cats to determine whether they were utilized. Groups of five cats were depleted of taurine by a resin (Colestipol®) diet, then given 6 dietary treatments containing (g/kg diet): 0.0, 0.4, or 0.8 taurine; or 0.98 or 1.96 cysteinesulfinic acid, or 0.4 taurine + 1.0 cysteic acid for 12 wk. Plasma and whole blood taurine concentrations and body weights were measured weekly. Concentration of taurine in semitendinosus muscle was measured initially, after 2 wk of taurine depletion (after resin-diet), and monthly thereafter. The resin diet decreased concentrations of taurine in plasma, whole blood, and muscle to 0.20, 0.49, and 0.37 of initial values, respectively. Cysteinesulfinic acid diets resulted in no significant (P > 0.05) increase in the concentration of taurine in plasma, whole blood, or muscle, and no increased excretion of cysteinesulfinate or taurine in urine or feces. Cats fed the diets containing 1.0 g cysteic acid + 0.4 g taurine, or 0.8 g taurine/kg diet had similar concentrations of taurine in plasma, whole blood, and muscle. Aminotransferase activity for cysteinesulfinic acid in the liver and intestinal mucosa of cats and rats was higher than that for aspartic or cysteic acids. Transamination of dietary cysteinesulfinic acid to β-sulfinylpyruvate (which spontaneously decomposes), rather than decarboxylation is postulated as the basis for no detectable conversion to taurine. In contrast, cysteic acid is reversibly transaminated to β-sulfopyruvate which is stable and thereby is a precursor for taurine in cats.

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

Alveolar macrophages isolated by pulmonary lavage from partially taurine-depleted rats demonstrated 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% beta-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.

Effects of taurine depletion on cell migration and NCAM expression in cultures of dissociated mouse cerebellum and N2A cells.

Cultures of dissociated cerebellum from 5- to 6-day-old mice as well as of the N2A neuronal cell line were exposed to guanidino ethane sulfonate (GES, 2-5 mM) to reduce the cellular taurine content. Control cultures were kept in culture medium or medium containing 2-5 mM GES plus 2-5 mM taurine to restore the intracellular taurine content. Taurine depletion led to changes in the expression of certain splice variants of NCAM mRNA such as the AAG and the VASE containing forms, while no differences were seen in the expression of the three forms of NCAM protein. In the N2A cells taurine depletion led to a decreased migration rate of the cells. The results suggest that the reduced migration rate of neurons caused by taurine depletion may be correlated to changes in expression of certain adhesion molecules such as NCAM. Moreover, taurine appears to be involved in regulation of transcription processes.

Shape and size changes induced by taurine depletion in neonatal cardiomyocytes.

Taurine is a very important organic osmolyte in most adult cells. Because of this property it has been proposed that large changes in the intracellular content of taurine can osmotically stress the cell, causing changes in its size and shape. This hypothesis was examined by measuring cell dimensions of taurine deficient cardiomyocytes using confocal microscopy. Incubation of isolated neonatal rat myocytes with medium containing 5 mM beta-alanine led to a 55% decrease in intracellular taurine content. Associated with the loss of taurine was a reduction in cell size. Two factors contributed to the change in cell size. First, there was a shift in cell shape, favoring the smaller of the two cellular configurations commonly found in the myocyte cell culture. Second, the size of the polyhedral configuration was reduced after beta-alanine treatment. These same two events also contributed to size reduction in cardiomyocytes incubated with medium containing 30 mM mannitol. Nonetheless, some qualitative differences exist between cells osmotically stressed by increasing the osmolality of the incubation medium and decreasing intracellular osmolality. The results support a role for taurine in the regulation of osmotic balance in the neonatal cardiomyocyte.

Effect of taurine depletion on angiotensin II-mediated modulation of myocardial function.

Taurine depletion was induced by either incubation of isolated myocytes with 5 mM beta-alanine or feeding rats with water containing 3% beta-alanine. Hearts of taurine depleted rats exhibited an impairment in myocardial relaxation, associated with a decrease in Na(+)-Ca2+ exchanger activity. Exposure of the heart to angiotensin II, an activator of the Na(+)-Ca2+ exchanger, eliminated the relaxation defect. In agreement with the contractile results, taurine depletion prolonged the calcium transient, an effect which was partially eliminated by exposure to angiotensin II. Although peak systolic [Ca2+]i was modestly depressed in the taurine depleted myocyte, peak ventricular pressure was normal. This may be related to an elevation in pHi induced by taurine depletion. Angiotensin II had little effect on contractility of the taurine depleted heart, presumably because of two opposing effects, a reduction in pHi and an increase in [Ca2+]i. Thus, taurine depletion alters contractile function and ion transport and both of these effects are modulated by exposure of the heart to angiotensin II.

Extensive taurine depletion and retinal degeneration in cats treated with beta-alanine for 40 weeks.

It has now been established that cats are dependent on dietary sources of taurine to maintain their body reserve, and when deprived, they develop a variety of disorders including retinal degeneration, myocardial failure, depressed immune responsiveness and extensive reproductive deficits37,38,39. Feline central retinal degeneration, a photoreceptor degenerative condition originally described as bilaterally symmetrical generalized focal lesions of unknown etiology3,4,26, was among the first to be clearly linked to taurine deficiency16. The small incipient lesions visible by fundus ophthalmoscope as hyper-reflective round or oval foci in the area centralis, extend nasally and temporally in advanced stages of taurine deprivation accompanied by significant reductions in rod and cone ERG amplitudes5,6,34. The progression of retinal degeneration, however inevitable, is a relatively slow process and takes at least 6 to 12 months for cats fed a completely taurine-free diet to show the first signs. Moreover, tissue taurine levels are lowered only to the point that equilibrium with biosynthesized taurine is reached, with considerable individual variation, no matter how long cats are maintained on such a diet. In an attempt to reduce tissue taurine levels further, we provided adult female cats with β-alanine which competes with taurine for the same transport system, thereby limiting taurine uptake21,25. Previously, we reported that tissue taurine concentrations were greatly reduced while large amounts of β-alanine accumulated in visceral tissues and neural tissues of acutely taurine-depleted cats after 20 weeks of ß-alanine treatment42. The morphological changes associated with photoreceptor degeneration in the retinas of these cats were considerably more extensive and widespread than any described in cats rendered taurine-deficient by means of taurine-free diet alone17,40. In the present report we describe the consequence of extreme taurine depletion attained by extending the period of ß-alanine treatment to 40 weeks.KeywordsOuter SegmentRetinal DegenerationOuter Nuclear LayerPhotoreceptor DegenerationTaurine ConcentrationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.