Protective role of taurine against oxidative stress (Review).

Taurine is a fundamental mediator of homeostasis that exerts multiple roles to confer protection against oxidant stress. The development of hypertension, muscle/neuro­â€‹associated disorders, hepatic cirrhosis, cardiac dysfunction and ischemia/reperfusion are examples of some injuries that are linked with oxidative stress. The present review gives a comprehensive description of all the underlying mechanisms of taurine, with the aim to explain its anti­oxidant actions. Taurine is regarded as a cytoprotective molecule due to its ability to sustain normal electron transport chain, maintain glutathione stores, upregulate anti­oxidant responses, increase membrane stability, eliminate inflammation and prevent calcium accumulation. In parallel, the synergistic effect of taurine with other potential therapeutic modalities in multiple disorders are highlighted. Apart from the results derived from research findings, the current review bridges the gap between bench and bedside, providing mechanistic insights into the biological activity of taurine that supports its potential therapeutic efficacy in clinic. In the future, further clinical studies are required to support the ameliorative effect of taurine against oxidative stress.

GABAA Receptors and Maternally Derived Taurine Regulate the Temporal Specification of Progenitors of Excitatory Glutamatergic Neurons in the Mouse Developing Cortex.

Temporal specification of the neural progenitors (NPs) producing excitatory glutamatergic neurons is essential for histogenesis of the cerebral cortex. Neuroepithelial cells, the primary NPs, transit to radial glia (RG). To coincide with the transition, NPs start to differentiate into neurons, undergoing a switch from symmetric to asymmetric cell division. After the onset of neurogenesis, NPs produce layer-specific neurons in a defined order with precise timing. Here, we show that GABAA receptors (GABAARs) and taurine are involved in this regulatory mechanism. Foetal exposure to GABAAR-antagonists suppressed the transition to RG, switch to asymmetric division, and differentiation into upper-layer neurons. Foetal exposure to GABAAR-agonists caused the opposite effects. Mammalian foetuses are dependent on taurine derived from the mothers. GABA and taurine function as endogenous ligands for GABAARs. Ca2+ imaging showed that NPs principally responded to taurine but not GABA before E13. The histological phenotypes of the taurine transporter knockout mice resembled those of the mice foetally exposed to GABAAR-antagonists. Foetal exposure to GABAAR-modulators resulted in considerable alterations in offspring behavior like core symptoms of autism. These results show that taurine regulates the temporal specification of NPs and that disrupting the taurine-receptor interaction possibly leads to neurodevelopmental disorders.

Taurine chloramine selectively regulates neutrophil degranulation through the inhibition of myeloperoxidase and upregulation of lactoferrin.

Taurine is a free amino acid rich in neutrophils, and neutrophils play an important role in the forefront defense against infection. Upon neutrophil activation, taurine reacts with hypochlorous acid (HOCl/OCl-) produced by the myeloperoxidase (MPO) system and gets converted to taurine chloramine (Tau-Cl). Neutrophils have three types of granules, of which the primary granule MPO, secondary granule lactoferrin, and tertiary granule matrix metalloproteinase (MMP)-9 are released into the extracellular space by a process called degranulation. MPO produces hypochlorous acid to kill microorganisms, and the released MPO forms neutrophil extracellular traps (NETs) with released chromatin. Excessive secretion of MPO causes oxidative damage to the surrounding tissues. Lactoferrin exerts antioxidant activity, prevents pro-inflammatory pathway activation, sepsis, and tissue damages, and delays neutrophil apoptosis. Our experimental results show that neutrophils released small amount of granules in an inactive state, and phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionine-leucyl-phenylalanine induced neutrophil degranulation. Tau-Cl inhibited the PMA-induced degranulation of MPO and formation of NETs. While Tau-Cl increased the degranulation of lactoferrin, it had no effect on MMP-9 degranulation. MPO negatively regulated the production of macrophage inflammatory protein (MIP)-2, which stimulates the degranulation and migration of neutrophils. Tau-Cl abrogated MIP-2 expression, suggestive of its inhibitory effect on MPO release. The increase in the intracellular level of MPO may negatively regulates MIP-2 expression, thereby contributing to the further regulation of neutrophil degranulation and migration. Here, we suggest that Tau-Cl selectively inhibits MPO degranulation and stimulates lactoferrin degranulation from neutrophils, thereby protecting inflamed tissues from oxidative damage induced by excessively released MPO.

Thiotaurine: From Chemical and Biological Properties to Role in H2S Signaling.

In the last decade thiotaurine, 2-aminoethane thiosulfonate, has been investigated as an inflammatory modulating agent as a result of its ability to release hydrogen sulfide (H2S) known to play regulatory roles in inflammation. Thiotaurine can be included in the "taurine family" due to structural similarity to taurine and hypotaurine, and is characterized by the presence of a sulfane sulfur moiety. Thiotaurine can be produced by different pathways, such as the spontaneous transsulfuration between thiocysteine - a persulfide analogue of cysteine - and hypotaurine as well as in vivo from cystine. Moreover, the enzymatic oxidation of cysteamine to hypotaurine and thiotaurine in the presence of inorganic sulfur can occur in animal tissues and last but not least thiotaurine can be generated by the transfer of sulfur from mercaptopyruvate to hypotaurine catalyzed by a sulfurtransferase. Thiotaurine is an effective antioxidant agent as demonstrated by its ability to counteract the damage caused by pro-oxidants in the rat. Recently, we observed the influence of thiotaurine on human neutrophils functional responses. In particular, thiotaurine has been found to prevent human neutrophil spontaneous apoptosis suggesting an alternative or additional role to its antioxidant activity. It is likely that the sulfane sulfur of thiotaurine may modulate neutrophil activation via persulfidation of target proteins. In conclusion, thiotaurine can represent a biologically relevant sulfur donor acting as a biological intermediate in the transport, storage and release of sulfide.

Roles of taurine in cognitive function of physiology, pathologies and toxication.

Taurine is a key functional amino acid with many functions in the nervous system. The effects of taurine on cognitive function have aroused increasing attention. First, the fluctuations of taurine and its transporters are associated with cognitive impairments in physiology and pathology. This may help diagnose and treat cognitive impairment though mechanisms are not fully uncovered in existing studies. Then, taurine supplements in cognitive impairment of different physiologies, pathologies and toxicologies have been demonstrated to significantly improve and restore cognition in most cases. However, elevated taurine level in cerebrospinal fluid (CSF) by exogenous administration causes cognition retardations only in physiologically sensitive period between the perinatal to early postnatal period. In this review, taurine levels are summarized in different types of cognitive impairments. Subsequently, the effects of taurine supplements on cognitions in physiology, different pathologies and toxication of cognitive impairments (e.g. aging, Alzheimer' disease, streptozotocin (STZ)-induced brain damage, ischemia model, mental disorder, genetic diseases and cognitive injuries of pharmaceuticals and toxins) are analyzed. These data suggest that taurine can improve cognition function through multiple potential mechanisms (e.g. restoring functions of taurine transporters and γ-aminobutyric acid (GABA) A receptors subunit; mitigating neuroinflammation; up-regulating Nrf2 expression and antioxidant capacities; activating Akt/CREB/PGC1α pathway, and further enhancing mitochondria biogenesis, synaptic function and reducing oxidative stress; increasing neurogenesis and synaptic function by pERK; activating PKA pathway). However, more mechanisms still need explorations.

Taurine: A Regulator of Cellular Redox Homeostasis and Skeletal Muscle Function.

Taurine is a nonproteinogenic ß-aminosulfonic acid. Important dietary sources of taurine are fish and seafood. Taurine interacts with ion channels, stabilizes membranes, and regulates the cell volume. These actions confirm its high concentrations in excitable tissues like retina, neurons, and muscles. Retinal degeneration, cardiomyopathy, as well as skeletal muscle malfunction are evident in taurine-deficient phenotypes. There is evidence that taurine counteracts lipid peroxidation and increases cellular antioxidant defense in response to inflammation. In activated neutrophils, taurine reacts with hypochloric acid to form taurine chloramine, which triggers the Kelch-like ECH-associated protein 1-nuclear factor E2-related factor 1 (Keap1-Nrf2) pathway. Consequently, Nrf2 target genes, such as heme oxygenase-1 and catalase, are induced. Furthermore, taurine may prevent an overload of reactive oxygen species (ROS) directly by an inhibition of ROS generation within the respiratory chain. Taurine affects mitochondrial bioenergetics and taurine-deficient mice exhibit an impaired exercise performance. Moreover, some studies demonstrate that taurine enhances the glycogen repletion in the postexercise recovery phase. In the case of taurine deficiency, many studies observed a phenotype known in muscle senescence and skeletal muscle disorders. Overall, taurine plays an important role in cellular redox homeostasis and skeletal muscle function.

Taurine is Involved in Energy Metabolism in Muscles, Adipose Tissue, and the Liver.

Energy metabolism is a basic and general process, by which the body acquires and uses energy to maintain normal function, and taurine plays a vital role in energy metabolism. Taurine deficiency may cause a weak energy metabolism and energy metabolism dysfunction. Taurine biosynthetic ability is limited, and its supplementation in the diet can strengthen energy metabolism in muscle performance, cardiac function, liver activity, and adipose tissue. Combining taurine with other drugs may have a superior effect in energy metabolism. In many metabolic disorders, taurine, or the combination of taurine with other drugs, also functions as a repair treatment for damaged tissues, and acts as a promoter for the balance of energy metabolism. The present study discusses the potential roles of taurine in energy metabolism.

Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration.

Purpose: To examine if light exposure exacerbates retinal neuronal loss induced by taurine depletion. Methods: Albino rats received ß-alanine in the drinking water to induce taurine depletion. One month later, half of the animals were exposed to white light (3000 lux) continuously for 48 hours and the rest remained in normal environmental conditions. A control group of animals nontreated with ß-alanine also was prepared, and half of them were exposed to light using the same protocol. All the animals were processed 2 months after the beginning of the experiment. Retinas were dissected as wholemounts and immunodetected with antibodies against Brn3a, melanopsin, S-opsin, and L-opsin to label different retinal populations: Brn3a+ retinal ganglion cells (RGCs) (image-forming RGCs), m+RGCs (non-image-forming RGCs), and S- and L/M-cones, respectively. Results: Light exposure did not affect the numbers of Brn3a+RGCs or m+RGCs but diminished the numbers of S- and L/M-cones and caused the appearance of rings devoid of cones, mainly in an "arciform" area in the superotemporal retina. Taurine depletion caused a diminution of all the studied populations, with m+RGCs the most affected, followed by S-cones. Light exposure under taurine depletion increased photoreceptor degeneration but did not seem to increase Brn3a+RGCs or m+RGCs loss. Conclusions: Our results document that taurine is necessary for cell survival in the rat retina and even more under light-induced photoreceptor degeneration. Thus, taurine supplementation may help to prevent retinal degenerations, especially those that commence with S-cone degeneration or in which light may be an etiologic factor, such as inherited retinal degenerations, AMD, or glaucoma.

Understanding taurine CNS activity using alternative zebrafish models.

Taurine is a highly abundant "amino acid" in the brain. Despite the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action. In this context, we also highlight how zebrafish models of brain disorders may present interesting approaches to assess molecular mechanisms underlying positive effects of taurine in the brain. Finally, we outline recent advances in zebrafish drug screening that significantly improve neuropsychiatric translational researches and small molecule screens.

Persistent GABAA/C responses to gabazine, taurine and beta-alanine in rat hypoglossal motoneurons.

In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30µM), allopregnanolone (0.3µM) and midazolam (0.5µM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. The results indicate the involvement of hybrid heteromeric receptors, including at least a GABA receptor ρ subunit and a γ subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous ß amino acids, taurine and ß-alanine, which are released under various pathological conditions and show neuroprotective properties, were then studied. In the presence of the glycine receptor blocker strychnine (1µM), both taurine (0.3-1mM) and ß-alanine (0.3mM) activated sustained anionic currents, which were partly blocked by TPMPA (100µM). Thus, both ß amino acids activated ρ-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20µM) reduced responses to taurine and ß-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to ß-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and ß-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations.

Impact of taurine depletion on glucose control and insulin secretion in mice.

Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism.

The ubiquitin-proteasome system and autophagy are defective in the taurine-deficient heart.

Taurine depletion leads to impaired mitochondrial function, as characterized by reduced ATP production and elevated superoxide generation. These defects can fundamentally alter cardiomyocyte function and if left unchanged can result in cell death. To protect against these stresses, cardiomyocytes possess quality control processes, such as the ubiquitin-proteasome system (UPS) and autophagy, which can rejuvenate cells through the degradation of damaged proteins and organelles. Hence, the present study tested the hypothesis that reactive oxygen species generated by damaged mitochondria initiates UPS and autophagy in the taurine-deficient heart. Using transgenic mice lacking the taurine transporter (TauTKO) as a model of taurine deficiency, it was shown that the levels of ubiquitinated protein were elevated, an effect associated with a decrease in ATP-dependent 26S ß5 proteasome activity. Treating the TauTKO mouse with the mitochondria-specific antioxidant, mitoTEMPO, largely abolished the increase in ubiquitinated protein content. The TauTKO heart was also associated with impaired autophagy, characterized by an increase in the initiator, Beclin-1, and autophagosome content, but a defect in the generation of active autophagolysosomes. Although mitoTEMPO treatment only restores the oxidative balance within the mitochondria, it appeared to completely disrupt the crosstalk between the damaged mitochondria and the quality control processes. Thus, mitochondrial oxidative stress is the main trigger initiating the quality control systems in the taurine-deficient heart. We conclude that the activation of the UPS and autophagy is another fundamental function of mitochondria.

Role of taurine in the pathogenesis of obesity.

Taurine is a sulfur-containing amino acid that is present in mammalian tissues in millimolar concentrations. Taurine is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. The prevalence of obesity and being overweight continues to rise worldwide at an alarming rate. Obesity is associated with a higher risk of metabolic and cardiovascular diseases, cancer, and other clinical conditions. Ingestion of taurine has been shown to alleviate metabolic diseases such as hyperlipidemia, diabetes, hypertension, and obesity in animal models. A global epidemiological survey showed that 24-h urinary taurine excretion, as a marker of dietary taurine intake, was inversely associated with BMI, blood pressure, and plasma cholesterol in humans. In addition, taurine chloramine, an endogenous product derived from activated neutrophils, has been reported to suppress obesity-induced oxidative stress and inflammation in adipocytes. Synthetic activity and concentration of taurine in adipose tissues and plasma have been shown to decrease in humans and animals during the development of obesity, suggesting a relationship between taurine deficiency and obesity. In this review, I summarize the effects of taurine on the progression of obesity in animal models and humans. Furthermore, I discuss possible mechanisms underlying the antiobesity effects of taurine.

Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations.

Taurine is the most abundant amino acid in the retina. In the 1970s, it was thought to be involved in retinal diseases with photoreceptor degeneration, because cats on a taurine-free diet presented photoreceptor loss. However, with the exception of its introduction into baby milk and parenteral nutrition, taurine has not yet been incorporated into any commercial treatment with the aim of slowing photoreceptor degeneration. Our recent discovery that taurine depletion is involved in the retinal toxicity of the antiepileptic drug vigabatrin has returned taurine to the limelight in the field of neuroprotection. However, although the retinal toxicity of vigabatrin principally involves a deleterious effect on photoreceptors, retinal ganglion cells (RGCs) are also affected. These findings led us to investigate the possible role of taurine depletion in retinal diseases with RGC degeneration, such as glaucoma and diabetic retinopathy. The major antioxidant properties of taurine may influence disease processes. In addition, the efficacy of taurine is dependent on its uptake into retinal cells, microvascular endothelial cells and the retinal pigment epithelium. Disturbances of retinal vascular perfusion in these retinal diseases may therefore affect the retinal uptake of taurine, resulting in local depletion. The low plasma taurine concentrations observed in diabetic patients may further enhance such local decreases in taurine concentration. We here review the evidence for a role of taurine in retinal ganglion cell survival and studies suggesting that this compound may be involved in the pathophysiology of glaucoma or diabetic retinopathy. Along with other antioxidant molecules, taurine should therefore be seriously reconsidered as a potential treatment for such retinal diseases.

N-Acyl amino acids and their impact on biological processes.

Over the last two decades a large number of N-long-chain acyl amino acids have been identified in the mammalian body. The pharmacological activities of only a few of them have been investigated and some have been found to be of considerable interest. Thus arachidonoyl serine is vasodilatory and neuroprotective, arachidonoyl glycine is antinociceptive, and oleoyl serine rescues bone loss. However, the pathophysiological/biochemical roles of these amides are mostly unknown.

Mechanism of the protective action of taurine in toxin and drug induced organ pathophysiology and diabetic complications: a review.

Taurine (2-aminoethanesulfonic acid), a conditionally essential amino acid, is found in large concentrations in all mammalian tissues and is particularly abundant in aquatic foods. Taurine exhibits membrane stabilizing, osmoregulatory and cytoprotective effects, antioxidative properties, regulates intracellular Ca(2+) concentration, modulates ion movement and neurotransmitters, reduce the levels of pro-inflammatory cytokines in various organs and controls blood pressure. Recently, emerging evidence from the literature shows the effectiveness of taurine as a protective agent against several environmental toxins and drug-induced multiple organ injuries as the outcome of hepatotoxicity, nephrotoxicity, neurotoxicity, testicular toxicity and cardiotoxicity in several animal models. Besides, taurine is also effective in combating diabetes and its associated complications, including cardiomyopathy, nephropathy, neuropathy, retinopathy and atherosclerosis. These beneficial effects appear to be due to the multiple actions of taurine on cellular functions. This review summarizes the mechanism of the prophylactic role of taurine against several environmental toxins and drug-induced organ pathophysiology and diabetes.

Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain.

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.

Hypochlorous acid regulates neutrophil extracellular trap release in humans.

Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine.

An in vitro paradigm for diabetic cerebral oedema and its therapy: a critical role for taurine and water channels.

The pathophysiology of cerebral oedema (CE) in diabetic ketoacidosis (DKA) remains enigmatic. We investigated the role of the idiogenic osmol taurine and aquaporin channels in an in vitro model, the SH-SY5Y neuroblastoma cell line, by sequentially mimicking DKA-like hyperglycemia/hypertonicity and hypotonic fluid therapy. Exposure to DKA-like hyperosmolarity led to shrinkage, while hypotonic fluid exposure led to cell swelling and impaired viability. Low sodium compensated in part for elevated glucose, pointing to a critical role for overall osmolality. Taurine, was synthesized and retained intracellularly during DKA-like hypertonicity, and released during hypotonicity, in part mitigating neuronal swelling. Metabolic labeling showed that the rate of taurine release was inadequate to fully prevent neuronal swelling during hypotonic fluid therapy following DKA-like hypertonicity. Under these conditions, Aquaporin4 & 9 channels were respectively down and up-regulated. Our study provides further novel insights into molecular mechanisms contributing to CE in DKA and its therapy.

The synthesis and role of taurine in the Japanese eel testis.

In teleost fish, the progestin 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) is an essential component of the spermatogenesis pathway. In a series of investigations on the mechanisms underlying progestin-stimulated spermatogenesis, we have found that DHP up-regulates the expression of cysteine dioxygenase1 (CDO1) in the Japanese eel testis. CDO1 is one of the enzymes involved in the taurine biosynthesis pathway. To evaluate whether taurine is synthesized in the eel testis, cysteine sulfinate decarboxylase (CSD), another enzyme involved in taurine synthesis, was isolated from this species. RT-PCR and in vitro eel testicular culture revealed that although CSD was also expressed in eel testis, neither DHP nor other sex steroids affect CSD mRNA expression in a similar manner to CDO1. Using an in vitro eel testicular culture system, we further investigated the effects of DHP on taurine synthesis in the eel testis. HPLC analysis showed that DHP treatment significantly increases the taurine levels in the eel testis. These results suggest that DHP promotes taurine synthesis via the up-regulation of CDO1 mRNA expression during eel spermatogenesis. Furthermore, we observed from our analysis that although taurine does not induce complete spermatogenesis, it promotes spermatogonial DNA synthesis and the expression of Spo11, a meiosis-specific marker. These data thus suggest that taurine augments the effects of sex steroids in the promotion of spermatogonial proliferation and/or meiosis and hence that taurine plays important roles in spermatogenesis.