Taurine Abstracts 4

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Usefulness of taurine in chronic congestive heart failure and its prospective application.
            (Azuma et al., 1992) Download
We compared the effect of oral administration of taurine (3 g/day) and coenzyme Q10 (CoQ10) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echocardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ10-treated group.

Effect of taurine supplementation on exercise capacity of patients with heart failure.
            (Beyranvand et al., 2011) Download
BACKGROUND:  Taurine (2-aminoethanesulfonic acid) is a semi-essential amino acid found in mammalian tissues that is not involved in protein synthesis. The function of taurine is not completely understood. Some studies have demonstrated that taurine supplementation reduces death rate in rabbits with heart failure (HF) and diminishes HF severity in human models of congestive HF. In this study we have evaluated the effect of taurine supplementation on exercise capacity of patients with HF. METHODS:  A randomized single-blind placebo-controlled clinical trial was conducted on 29 patients with HF with left ventricular ejection fraction (LVEF) less than 50% who were in functional class II or III according to New York Heart Association classification. A total of 15 patients received taurine supplementation 500 mg three times a day while the remaining 14 patients received placebo for 2 weeks. All patients performed exercise tolerance test before and after taurine and placebo supplementation. RESULTS:  The mean age of patients was 60.57 ± 6.54 years, they were mostly male (26 of 29), and had mean LVEF of 29.27 ± 6.97%. There were no significant differences in terms of LVEF, body mass index, and also exercise time, metabolic equivalents (METS) and exercise distance before supplementation. Exercise time, METS, and exercise distance increased significantly in patients who received taurine supplement for 2 weeks (p-value<0.0001 for all), but did not increase significantly in patients who received placebo (p-values 0.379, 0.244, and 0.577 respectively). CONCLUSION:  Taurine supplementation in patients with HF who are taking standard medical treatment can increase their exercise capacity.

The effect of taurine supplementation on glucose homeostasis: the role of insulin-degrading enzyme.
            (Camargo et al., 2015) Download
Taurine is a semi-essential sulfur-containing amino acid derived from the metabolism of methionine and cysteine. Taurine controls several biological processes, including glucose homeostasis. The effects of taurine supplementation on insulin secretion and its effects on peripheral organs have been previously described. However, there are no data describing the effects of this amino acid on insulin clearance and the expression of insulin-degrading enzyme (IDE). Therefore, the aim of the present study was to assess the impact of taurine supplementation on IDE expression in the liver and on insulin clearance. Mice supplemented with taurine exhibited increased glucose tolerance and insulin sensitivity, as well as lower food intake and reduced fat pad compared with controls, but they presented no changes in the Lee index, body weight, or insulin secretion by pancreatic islets. In addition, taurine supplementation resulted in increased hepatic IDE expression, which may have affected insulin clearance. We hypothesize that supplementation with taurine, which is important for the control of glucose homeostasis, might stimulate hepatic IDE expression and insulin clearance, and this may explain the improvement in glucose tolerance, despite the lack of on effect on insulin secretion.

Taurine and the renal system.
            (Chesney et al., 2010) Download
Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, taurine plays a role in the renal cell cycle and apoptosis, and functions as an osmolyte during the stress response. The role of the kidney in adaptation to variations in dietary taurine intake and the regulation of taurine body pool size are described. Finally, the protective function of taurine against several kidney diseases is reviewed.


 

Role of AMP-activated protein kinase in healthy and diseased hearts.
            (Dolinsky and Dyck, 2006) Download
The heart is capable of utilizing a variety of substrates to produce the necessary ATP for cardiac function. AMP-activated protein kinase (AMPK) has emerged as a key regulator of cellular energy homeostasis and coordinates multiple catabolic and anabolic pathways in the heart. During times of acute metabolic stresses, cardiac AMPK activation seems to be primarily involved in increasing energy-generating pathways to maintain or restore intracellular ATP levels. In acute situations such as mild ischemia or short durations of severe ischemia, activation of cardiac AMPK appears to be necessary for cardiac myocyte function and survival by stimulating ATP generation via increased glycolysis and accelerated fatty acid oxidation. Whereas AMPK activation may be essential for adaptation of cardiac energy metabolism to acute and/or minor metabolic stresses, it is unknown whether AMPK activation becomes maladaptive in certain chronic disease states and/or extreme energetic stresses. However, alterations in cardiac AMPK activity are associated with a number of cardiovascular-related diseases such as pathological cardiac hypertrophy, myocardial ischemia, glycogen storage cardiomyopathy, and Wolff-Parkinson-White syndrome, suggesting the possibility of a maladaptive role. Although the precise role AMPK plays in the diseased heart is still in question, it is clear that AMPK is a major regulator of cardiac energy metabolism. The consequences of alterations in AMPK activity and subsequent cardiac energy metabolism in the healthy and the diseased heart will be discussed.

Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation.
            (Franconi et al., 1995) Download
Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet aggregation induced by arachidonic acid in vitro at baseline and after oral taurine supplementation (1.5 g/d) for 90 d was also studied. Plasma and platelet taurine concentrations (mean +/- SEM) were lower in diabetic patients (65.6 +/- 3.1 mumol/L, or 0.66 +/- 0.07 mol/g protein) than in control subjects (93.3 +/- 6.3 mumol/L, or 0.99 +/- 0.16 mol/g protein, P < 0.01). After oral supplementation, both plasma and platelet taurine concentrations increased significantly in the diabetic patients, reaching the mean values of healthy control subjects. The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001, whereas after taurine supplementation it equaled the mean value for healthy control subjects (0.72 +/- 0.04 mmol). In in vitro experiments, taurine reduced platelet aggregation in diabetic patients in a dose-dependent manner, whereas 10 mmol taurine/L did not modify aggregation in healthy subjects.

Taurine increases hippocampal neurogenesis in aging mice.
            (Gebara et al., 2015) Download
Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

Taurine attenuates hippocampal and corpus callosum damage, and enhances neurological recovery after closed head injury in rats.
            (Gu et al., 2015) Download
The protective effects of taurine against closed head injury (CHI) have been reported. This study was designed to investigate whether taurine reduced white matter damage and hippocampal neuronal death through suppressing calpain activation after CHI in rats. Taurine (50 mg/kg) was administered intravenously 30 min and 4 h again after CHI. It was found that taurine lessened the corpus callosum damage, attenuated the neuronal cell death in hippocampal CA1 and CA3 subfields and improved the neurological functions 7 days after CHI. Moreover, it suppressed the over-activation of calpain, enhanced the levels of calpastatin, and reduced the degradation of neurofilament heavy protein, myelin basic protein and αII-spectrin in traumatic tissue 24 h after CHI. These data confirm the protective effects of taurine against gray and white matter damage due to CHI, and suggest that down-regulating calpain activation could be one of the protective mechanisms of taurine against CHI.


 

Taurine enhances the growth of neural precursors derived from fetal human brain and promotes neuronal specification.
            (Hernández-Benítez et al., 2013) Download
Taurine is present at high concentrations in the fetal brain and is required for optimal brain development. Recent studies have reported that taurine causes increased proliferation of neural stem/progenitor neural cells (neural precursor cells, NPCs) obtained from embryonic and adult rodent brain. The present study is the first to show that taurine markedly increases cell numbers in cultures and neuronal generation from human NPCs (hNPCs). hNPCs obtained from 3 fetal brains (14-15 weeks of gestation) were cultured and expanded as neurospheres, which contained 76.3% nestin-positive cells. Taurine (5-20 mM) increased the number of hNPCs in culture, with maximal effect found at 10 mM and 4 days of culture. The taurine-induced increase ranged from 57 to 188% in the 3 brains examined. Taurine significantly enhanced the percentage of neurons formed from hNPCs under differentiating conditions, with increases ranging from 172 to 480% over controls without taurine. Taurine also increased the cell number and neuronal generation in cultures of the immortalized human cell line ReNcell VM. These results suggest that taurine has a positive influence on hNPC growth and neuronal formation.

Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease.
            (Kim et al., 2014) Download
Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.


 

Taurine in 24-h Urine Samples Is Inversely Related to Cardiovascular Risks of Middle Aged Subjects in 50 Populations of the World.
            (Sagara et al., 2015) Download
We previously showed that 24-h urinary taurine (Tau) excretion was inversely associated with mortality due to coronary heart diseases (CHD) and stroke. The aim of this study was to examine the association between 24-h urinary Tau/creatinine (Cre) ratio and cardiovascular disease risk factors, including body mass index (BMI), blood pressure (BP), serum total cholesterol (TC) and prevalence of obesity, hypertension and hypercholesterolemia.
A cross sectional analysis was conducted among 4,211 participants (2,120 men and 2,091 women) aged 48–56 from 50 population samples of 22 countries in the World Health Organization-coordinated Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study (1985–1994).
According to linear regression analyses adjusted for traditional risk factors such as age, sex and anti-hypertensive treatment, Tau/Cre was inversely associated with BMI, systolic BP, diastolic BP and TC (P for linear trend <0.001, respectively). These associations were not markedly altered by further adjustment for 24-h urinary sodium/Cre, potassium/Cre, calcium/Cre, magnesium/Cre and cohort effects. After adjusting for the traditional risk factors, the prevalence of obesity, hypertension and hypercholesterolemia among the subjects within the lowest quintile of the Tau/Cre ratio was 2.84 (95 % CI: 2.04, 3.96; P for trend <0.001), 1.22 (95 % CI: 0.98, 1.51; P < 0.05) and 2.20 (95 % CI: 1.73, 2.80; P < 0.001) times higher than that in the subjects within the highest quintile. These associations were not appreciably altered by further adjustment for other 24-h urinary markers and cohort effects.
In conclusion, higher Tau/Cre was associated with lower cardiovascular disease risk factors, including BMI, BP, TC, obesity, hypertension and hypercholesterolemia.

Physiological roles of taurine in heart and muscle.
            (Schaffer et al., 2010) Download
Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals.

Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain.
            (Shivaraj et al., 2012) Download
Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems.


 

Taurine enhances excitability of mouse cochlear neural stem cells by selectively promoting differentiation of glutamatergic neurons over GABAergic neurons.
            (Wang et al., 2015) Download
Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues, and has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in inner ear neural development is still largely unknown. Here we report that taurine enhanced the viability and proliferation of in vitro mouse cochlear neural stem cell culture, as well as improved neurite outgrowth. Moreover, prolonged taurine treatment also increased the neural electrical activity by escalating changes of intracellular calcium concentration, the number of spontaneous Ca(2+) oscillations in cells, and the frequencies of Ca(2+) spikes. Most importantly, we found that this escalated neural excitability by taurine was due to combined effect of increase in the population of excitatory glutamatergic neuron and decrease in inhibitory GABAergic neuron population. This is the first report on the effect of taurine to selectively promote neural stem cell differentiation by altering neuron type commitment. Our study has supported the potential of taurine as treatment against hearing loss caused by neuron degeneration, or even as an agent to improve sensitivity of hearing by increasing overall excitability of auditory nervous system.

Therapeutic effect of taurine against aluminum-induced impairment on learning, memory and brain neurotransmitters in rats.
            (Wenting et al., 2014) Download
The aim of the study was to demonstrate the therapeutic effect of taurine against aluminum (Al)-induced neurological disorders in rats. Forty-two Wistar rats were randomly allotted into six groups: control (saline only), Al exposure (281.4 mg/kg/day for 1 month), Al + taurine (Al administration as previously plus taurine, doses were 200, 400 and 800 mg/kg/day, respectively, for the next 1 month) and prevention group (along with the Al administration as previously, 400 mg/kg/day taurine was treated for 1 month. During the next 1 month, rats were given taurine 400 mg/kg/day only). Starting from the sixth week, the body weight gain was significantly reduced in Al exposure group compared with saline (P < 0.05), and at the eighth week, the gain in prevention group was increased compared with Al (P < 0.05). Brain coefficient was gained in Al exposure compared with saline or prevention group (P < 0.05). Al exposure resulted in learning and memory impairment by increasing the escape latency and searching distance, meanwhile, decreasing the swimming time in the quadrant of platform and the numbers of crossing the platform (P < 0.05). Unsurprisingly, taurine treatment (400, 800 mg/kg/day and prevention) significantly protected against Al-induced brain dysfunction (P < 0.05). The Al exposure led to significant decreases in levels of γ-GABA and Tau, meanwhile, increased in level of Asp and Glu compared with saline (P < 0.05). And yet, taurine treatment partially reversed the deteriorated changes. The results suggested that taurine probably has neuroprotective effect against Al-induced learning, memory and brain neurotransmitters dysfunction.

Reduced plasma taurine level in Parkinson's disease: association with motor severity and levodopa treatment.
            (Zhang et al., 2015) Download
PURPOSE:  This study aimed to evaluate the level of taurine in plasma, and its association with the severity of motor and non-motor symptoms (NMS) and chronic levodopa treatment in Parkinson's disease (PD). PATIENTS AND METHODS:  Plasma taurine level was measured in treated PD (tPD), untreated PD (ntPD) and control groups. Motor symptoms and NMS were assessed using the Unified Parkinson's Disease Rating Scale, the short form of the McGill Pain Questionnaire, the Hamilton Depression Scale, the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms and the Pittsburgh Sleep Quality Index. Longtime exposure to levodopa was indicated by its approximate cumulative dosage. RESULTS:  The plasma taurine levels of PD patients were decreased when compared with controls and negatively associated with motor severity but not NMS. Moreover, tPD patients exhibited lower levels of plasma taurine than ntPD patients. Interestingly, plasma taurine levels negatively correlated with cumulative levodopa dosage in tPD. After controlling for potential confounders, the association between taurine and levodopa remained significant. CONCLUSION:  Our study supports that taurine may play important roles in the pathophysiology of PD and the disturbances caused by chronic levodopa administration.


 

References

Azuma, J, A Sawamura, and N Awata (1992), ‘Usefulness of taurine in chronic congestive heart failure and its prospective application.’, Jpn Circ J, 56 (1), 95-99. PubMed: 1538580
Beyranvand, MR, et al. (2011), ‘Effect of taurine supplementation on exercise capacity of patients with heart failure.’, J Cardiol, 57 (3), 333-37. PubMed: 21334852
Camargo, RL, et al. (2015), ‘The effect of taurine supplementation on glucose homeostasis: the role of insulin-degrading enzyme.’, Adv Exp Med Biol, 803 715-24. PubMed: 25833539
Chesney, RW, X Han, and AB Patters (2010), ‘Taurine and the renal system.’, J Biomed Sci, 17 Suppl 1 S4. PubMed: 20804616
Dolinsky, VW and JR Dyck (2006), ‘Role of AMP-activated protein kinase in healthy and diseased hearts.’, Am J Physiol Heart Circ Physiol, 291 (6), H2557-69. PubMed: 16844922
Franconi, F., et al. (1995), ‘Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation’, Am J Clin Nutr, 61 (5), 1115-19. PubMed: 7733037
Gebara, E, et al. (2015), ‘Taurine increases hippocampal neurogenesis in aging mice.’, Stem Cell Res, 14 (3), 369-79. PubMed: 25889858
Gu, Y, et al. (2015), ‘Taurine attenuates hippocampal and corpus callosum damage, and enhances neurological recovery after closed head injury in rats.’, Neuroscience, 291 331-40. PubMed: 25290011
Hernández-Benítez, R, et al. (2013), ‘Taurine enhances the growth of neural precursors derived from fetal human brain and promotes neuronal specification.’, Dev Neurosci, 35 (1), 40-49. PubMed: 23466467
Kim, HY, et al. (2014), ‘Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer’s disease.’, Sci Rep, 4 7467. PubMed: 25502280
Sagara, M, et al. (2015), ‘Taurine in 24-h Urine Samples Is Inversely Related to Cardiovascular Risks of Middle Aged Subjects in 50 Populations of the World.’, Adv Exp Med Biol, 803 623-36. PubMed: 25833532
Schaffer, SW, et al. (2010), ‘Physiological roles of taurine in heart and muscle.’, J Biomed Sci, 17 Suppl 1 S2. PubMed: 20804594
Shivaraj, MC, et al. (2012), ‘Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain.’, PLoS One, 7 (8), e42935. PubMed: 22916184
Wang, Q, et al. (2015), ‘Taurine enhances excitability of mouse cochlear neural stem cells by selectively promoting differentiation of glutamatergic neurons over GABAergic neurons.’, Neurochem Res, 40 (5), 924-31. PubMed: 25725997
Wenting, L, et al. (2014), ‘Therapeutic effect of taurine against aluminum-induced impairment on learning, memory and brain neurotransmitters in rats.’, Neurol Sci, 35 (10), 1579-84. PubMed: 24770980
Zhang, L, et al. (2015), ‘Reduced plasma taurine level in Parkinson’s disease: association with motor severity and levodopa treatment.’, Int J Neurosci, 1-7. PubMed: 26004911