Protection Of Taurine Research Articles

Protection of Taurine Against Neurotoxicity Induced by Arsenic in Primary Cortical Neurons.

Our group previously reported that taurine has a protective capacity on the hippocampus and cerebellum of arsenic (As)-exposed mouse. In the present study, we explore whether taurine demonstrates protection against As toxicity in primary cortical neurons. Primary cortical neurons were exposed to various concentrations of arsenite and cell viability was assessed to confirm the toxicity of As on cortical neurons. The protection of taurine was examined after primary cortical neurons were treating with arsenite and taurine for 24h. The cell viability was examined by MTT and caspase-3 activity assay. The expression of Bax and Bcl-2 was determined by western blot. The results showed that As exposure reduced cell viability and enhanced the activity of caspase-3, which were markedly inhibited by taurine treatment. The expression of Bax and Bcl-2 were disturbed by As exposure, which were reversed by taurine. These results indicated that taurine expose protective effect on As-exposed primary cortical neurons and its mechanism maybe involved the regulation of Bax/Bcl-2.

The Protection of Taurine on Abnormal Expression of Deiodinase 3 Induced by BDE 209 in JEG Cells Under the Normal Culture Conditions.

Taurine is an important amino acid for the growth and development of the central nervous system and plays an important role in the development of the nervous system. Many studies have shown that taurine can prevent and repair neurodevelopmental damage, and its mechanism has also become a research hotspot. While most studies focus on nerve cells, less on placental cells that are closely related to early neurodevelopment (developmental neurotoxicity) by modulating fetal circulation level of thyroid hormones. Studies have shown that exposure of placental cells to the common environmental endocrine disruptor BDE 209 during early pregnancy may lead to developmental neurotoxicity due to thyroid hormone interference caused by abnormal expression of deiodinases. Therefore, in this study, the placenta-derived JEG cells cultured at 95% air/5% CO2 was used as a in vitro model, and the potential protection from taurine on BDE 209-mediated cytotoxicity was examined. When BDE 209 was found to cause a decrease in cell viability and disturbance in the gene and protein expressions of placental deiodinase 3, pretreatment of the JEG cells with taurine can moderately reduce the BDE 209-meditated cytotoxicity, and restore gene and protein expressions of placental deiodinase, so that thyroid hormone levels tend to be normal in cell culture medium. Our data suggest that taurine may have some protection on the developmental neurotoxicity caused by BDE 209.

Alteration of Placental Deiodinase 3 Expression by BDE 209 and Possible Protection by Taurine in Human Placenta-Derived JEG Cells Under Hypoxia.

Thyroid hormones are key hormones involved in growth and development. Changes in their levels can cause embryonic brain developmental damage in the first trimester. Studies have shown that polybrominated diphenyl ethers (PBDEs) have developmental neurotoxicity as environmental pollutants, and exposure during pregnancy can cause irreversible brain damage in offspring, similar to the interference effects of thyroid hormones, but its mechanism has not yet been understood. Since the physiological environment for placental cells is highly hypoxic, in the current study, the human placenta-derived JEG cells were cultured at 1% oxygen, 4% carbon dioxide and 94% nitrogen, to reflect in vivo scenario, and the possible protection of taurine on BDE 209-mediated toxicity in JEG cells was studied. Our data showed that different concentrations of BDE 209 can have profound effects on cell viability and placental deiodinase 3 expression under hypoxic culture condition. Taurine was found to improve BDE 209-induced reductions in cell viability and altered gene and protein expressions of placental deiodinases. The results provide a reference for the establishment of early biomarkers and effective preventive measures.

Taurine Supplementation Ameliorates Arsenic-Induced Hepatotoxicity and Oxidative Stress in Mouse.

We previously reported that taurine treatment inhibited arsenic (As)-induced apoptosis in the liver of mice. This study was designed to explore the effect of taurine on liver function and its underlying mechanism in As-exposed mice. Mice were randomly divided into 3 groups, ten mice in each group. Group 1, control group, only orally received drinking water alone. Group 2, As intoxication group, was exposed to 4mg/L As2O3 via drinking water for 60days. Group 3, taurine protection group, was treated with 4mg/L As2O3 and 150mg/kg both. Taurine administration significantly revered the increases of alanine transaminase (ALT) and aspartate transaminase (AST) activities in serum. The decrease of glutathione (GSH) was inhibited with taurine treatment in the liver of As-exposed mice. At the same time, taurine significantly inhihibited As-induced enhancement of malondialdehyde (MDA) in the liver. Here we show that taurine protective effect on liver function in As-exposed mice maybe involve lipid peroxidation.

Anti-apoptotic Effect of Taurine on Schwann Cells Exposed to High Glucose In Vitro.

It was reported that apoptosis of Schwann cells could increase in the diabetic rats. The studies showed that taurine inhibited apoptosis in a variety of cells. However, there were few reports on studying the protection of taurine against apoptosis of Schwann cells induced by high glucose (HG) and the underlying mechanism. In our study, the cells were divided into five groups: Control: the normal medium; HG group: 50mM high glucose; T1: 50mM high glucose+Taurine (10mM) group; T2: 50mM high glucose+Taurine (20mM) group; T3: 50mM high glucose+Taurine (40mM) group. We used MTT and Tunel assays to measure the cell viability and apoptosis, respectively. Then, we also used western blotting to detect the protein levels of apoptosis-related protein. The results demonstrate that taurine promoted cell viability and decreased apoptosis in RSC96 cells exposed to HG. Furthermore, taurine markedly improved imbalance of Bax and Bcl-2, inhibited the translocation of Cytochrome C (Cyt C) from mitochondria to cytosol and reduced caspase-3 activity in HG-induced RSC96 cells. Our results indicate that taurine protect against apoptosis of Schwann cells induced by HG via inhibiting mitochondria-dependent caspase-3 pathway.

Effect of Taurine on Alterations in Deiodinase 3 Expression Induced by BDE 209 in Human Neuroblasoma-Derived SK-N-AS Cells.

PBDEs (stands for polybrominated diphenyl ethers) are extensively utilized flame retardants, and BDE 209 is one of the most widely used congeners. Studies have suggested the general toxic effects of PBDEs on the endocrine system and neural development. Our previous studies found that BDE 209 changed Type 3 iodothyronine deiodinase (Dio 3) expression in human SK-N-AS neuroblastoma cells. The current study was designed to examine the potential protection of taurine on alterations of Dio 3 expression induced by BDE 209 in SK-N-AS cells. Briefly, SK-N-AS cells were pretreated with taurine prior to the BDE 209 treatment, and the cell viability was evaluated by the MTT (methyl-thiazolyl-tetrazolium) assay. The disturbance or restoration in the levels of Dio 3 proteins and mRNA were observed separately by the western blot and qRT-PCR. Our data showed that taurine moderately attenuated BDE 209-mediated the loss of cell viability. Also, taurine moderately prevented the reduction in the Dio 3 protein expression and mRNA expression induced by BDE 209 in the SK-N-AS cells. Our findings indicated that taurine potentially provide the protection on PBDEs-induced toxicity on endocrine and neuro-development.

Protection of Taurine Against PFOS-Induced Neurotoxicity in PC12 Cells.

As a new member of persistent organic pollutants, the potent neurotoxicity of perfluorooctane sulfonates (PFOS) found in epidemiological studies and laboratory research has drawn increasing attention around the world. Previous studies showed that apoptosis driven by oxidative stress and autophagy were both observed in PFOS-induced toxicity. Taurine has been demonstrated to exert potent protections against oxidative stress as an efficient antioxidant. Whether taurine could protect against the PFOS neurotoxicity is not known. In the present study, PC12 cells were treated with several concentrations of PFOS (31.25, 250 μM) for 24 h. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was applied to assess the cell viability. DCFH-DA detector was used to explore the production of ROS. Caspase 3 activity was used to reflect the possible apoptosis pathway. The lyso-tracker red dying was invited to evaluate the autophagy. Our data showed that taurine could significantly reverse the decreased viability and the increased ROS production in PC12 cells treated with PFOS. Moreover, the increased autophagy and apoptosis elicited by PFOS in PC12 cells could also be attenuated by taurine. Collectively, our results indicate that taurine may be an effective antioxidant in fighting against PFOS cytotoxicity and therefore could potentially serve as a preventative and therapeutic agent for environmental pollution-related toxicities.

Protection of Taurine Against Impairment in Learning and Memory in Mice Exposed to Arsenic.

To evaluate protection of taurine against arsenic (As)-induced impairment of learning and memory as well as explore its protective mechanism, mice were divided into control, As and taurine protection groups. Mice of As exposure group exposed to drinking water containing 4ppm As2O3. Mice of taurine protective group received both 4ppm As2O3 and 150 mg taurine per kilogram. Mice of control group only drank double-distilled water. All animals were treated for 60days. Morphology of brain was observed by HE staining. Morris water maze (MWM) tests and step-down passive avoidance task were performed to examine cognition function. Moreover, expressions of some genes and proteins related to regulation learning and memory in brain were tested by Real Time RT-PCR and Western Blot. As a result, abnormal morphologic changes in brain tissue and poor performance in cognition functions were observed in As-exposed mice. The expression of TRβ protein, a regulator of CaMK IV gene, significantly decreased in brains of As-exposed mice than in controls. By contrast, impairment in learning and memory, change in brain morphology and disturbance in protein expression were significantly mitigated in mice of taurine protective group. Our results suggest that taurine supplementation protects against neurotoxicity induced by As in mice.

Protection of Taurine Against Arsenic-Induced DNA Damage of Mice Kidneys.

The purpose of this study was to explore the protective capacity of taurine on arsenic (As)-induced neurotoxicity. Thirty mice were used and ten rats in each group. We treated the As exposure group with 4 ppm As2O3 for 60 days by drinking water and the protective group with 4 ppm As2O3 and 150 mg/kg taurine. Drinking water was only given in the control group. Pathologic changes and DNA damage in the mice kidney were examined by HE staining, immunohistochemistry and comet assay. Abnormal morphological changes were found in the kidney of As exposed mouse. Moreover, 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and comet number, tail moment, and tail length of comet were markedly elevated in the As intoxication mice. However, histopathological changes and low expression of 8-OHdG were shown in the protective group. Our results indicate that supplementation of taurine protects against the histopathologic changes and DNA damage of mouse kidneys in As exposure group.

Taurine Protects Mouse Liver Against Arsenic-Induced Apoptosis Through JNK Pathway.

A great number of evidences demonstrated that the increased apoptosis is related to arsenic (As)-induced liver injury. The object of the present study was to explore the protection of taurine (Tau) against As-induced impairment in liver and the related mechanism. Adult mice were divided into control group, As exposure group and Tau protection group. The results of RT-PCR and WB showed that Tau treatment significantly reversed the disturbance of Bax and Bcl-2 expression. The release of cytochrome c and caspase-3 activation in liver both were prohibited by Tau in As-intoxicated mice. Furthermore, Tau markedly attenuated As-induced decrease of p-JNK level in mouse liver. These results indicated that Tau attenuated As-induced hepatic injury via JNK pathway.

Taurine inhibits 2,5-hexanedione-induced oxidative stress and mitochondria-dependent apoptosis in PC12 cells.

2,5-hexanedione (HD) is the ultimate neurotoxic metabolite of hexane, causing the progression of nerve diseases in human. It was reported that HD induced apoptosis and oxidative stress. Taurine has been shown to be a potent antioxidant. In the present study, we investigated the protection of taurine against HD-induced apoptosis in PC12 cells and the underlying mechanism. Our results showed the decreased viability and increased apoptosis in HD-exposed PC12 cells. HD also induced the disturbance of Bax and Bcl-2 expression, the loss of MMP, the release of mitochondrial cytochrome c and caspase-3 activation in PC12 cells. Moreover, HD resulted in an increase in reactive oxygen species (ROS) level and a decline in the activities of superoxidedismutase and catalase in PC12 cells. However, taurine pretreatment ameliorated the increased apoptosis and the alterations in key regulators of mitochondria-dependent pathway in PC12 exposed to HD. The increased ROS level and the decreased activities of the antioxidant enzymes in HD group were attenuated by taurine. These results indicate that pretreatment of taurine may, at least partly, prevent HD-induced apoptosis via inhibiting mitochondria-dependent pathway. It is also suggested that the potential of taurine against HD-induced apoptosis may benefit from its anti-oxidative property.

Neuroprotection of taurine against reactive oxygen species is associated with inhibiting NADPH oxidases

It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner.

Potential protection of taurine on antioxidant system and ATPase in brain and blood of rats exposed to aluminum.

Taurine (Tau) is used in clinical treatments but its protection of brains against aluminum-induced oxidative damage has been explored for the first time. The positive effect of Tau was studied on the activities of antioxidant enzymes and ATPase. Aluminum (Al) intake caused significant increasement of malondialdehyde (MDA) but reduction of the activities of superoxide dismutase, glutathione peroxidase (GSH-Px), Na(+)K(+)-ATPase and Mg(2+)-ATPase in brain compared to control group (P < 0.05). Tau administration, however, significantly reduced the MDA content, and increased the activities of aforementioned enzymes (P < 0.05). The MDA content was higher and the activities of GSH-Px, Ca(2+)-ATPase and Mg(2+)-ATPase lower in the blood of the Al-treated group' (P < 0.05), while Tau markedly decreased MDA content and improved the activities of GSH-Px and Ca(2+)-ATPase (P < 0.05). Tau may play a crucial role in the protection of antioxidant system and ATPase against Al-induced toxicity in brain and blood of rats.

Protective Effects of Taurine against Closed Head Injury in Rats

Taurine, an abundant amino acid in the nervous system, is reported to reduce ischemic brain injury in a dose-dependent manner. This study was designed to investigate whether taurine protected the brain against closed head injury (CHI) in rats. Taurine was administered intravenously 30 min after CHI. It was found that taurine lessened body-weight loss and improved neurological functions at 7 days after CHI. Moreover, it lowered brain edema and blood-brain barrier permeability, enhanced activity of superoxide dismutase and the level of glutathione, and reduced levels of malondialdehyde and lactic acid in traumatic tissue 24 h after CHI. In addition, it attenuated neuronal cell death in hippocampal CA1 and CA3 subfields 7 days after CHI. All of these effects were dose dependent. These data demonstrated the dose-dependent protection of taurine against experimental CHI and suggest that taurine treatment might be beneficial in reducing trauma-induced oxidative damage to the brain, thus showing the potential for clinical implications.

Mechanisms Underlying Taurine Protection Against Glutamate-Induced Neurotoxicity

Taurine appears to exert potent protections against glutamate (Glu)-induced injury to neurons, but the underlying molecular mechanisms are not fully understood. The possibly protected targets consist of the plasma membrane and the mitochondrial as well as endoplasmic reticulum (ER) membranes. Protection may be provided through a variety of effects, including the prevention of membrane depolarization, neuronal excitotoxicity and mitochondrial energy failure, increases in intracellular free calcium ([Ca2+]i), activation of calpain, and reduction of Bcl-2 levels. These activities are likely to be linked spatially and temporally in the neuroprotective functions of taurine. In addition, events that occur downstream of Glu stimulation, including altered enzymatic activities, apoptotic pathways, and necrosis triggered by the increased [Ca2+]i, can be inhibited by taurine. This review discusses the possible molecular mechanisms of taurine against Glu-induced neuronal injury, providing a better understanding of the protective processes, which might be helpful in the development of novel interventional strategies.

Taurine Protection against Endoplasmic Reticulum Stress in an Animal Stroke Model of Cerebral Artery Occlusion and Stroke Related conditions in Primary Neuronal Cell Culture

Taurine has been shown to provide protection against neurological diseases, such as Huntington's and stroke. We have shown that taurine can provide effective protection against Endoplasmic Reticulum (ER) stress induced by excitotoxicity or oxidative stress in PC12 cell line or primary neuronal cell cultures. In this study, we employed hypoxia/reoxygenation conditions for primary cortical neuronal cell cultures as well as the model of rat focal Middle Cerebral Artery Occlusion (MCAO). Using taurine greatly increased cell viability in primary neuronal cell culture and decreased the infarct area of sections at 6mm from 47.42±9.86% to 26.76 ± 6.91% in the MCAO model. Furthermore levels of the ER stress protein markers GRP78, Caspase12, CHOP and p‐IRE‐1 which were markedly increased in both the in vitro and in vivo models, significantly declined after taurine administration, suggesting that taurine may exert neuroprotection functions in both models. Moreover, taurine could downregulate the ratio of cleaved ATF6 and full length ATF6 in both models. In the animal model of stroke, taurine induced an upregulation of the Bcl‐2/Bax ratio and downregulation of Caspase‐3 protein activity indicating that it attenuates apoptosis in the core of the ischemic infarct. Our results show not only taurine elicits neuroprotection through the activation of the ATF6 and the IRE1 pathways, but also it can reduce apoptosis in these modelsGrant Funding Source: 09KW‐11, Department of Health, State of Florida

Therapeutic window of taurine against experimental stroke in rats

The dose-dependent protection of taurine against experimental stroke has been demonstrated previously. The objective of this study was to investigate the therapeutic window of taurine against experimental stroke, and the effects of delayed administration of taurine on inflammatory reaction in a rat model of stroke. Rats received 2-h ischemia by intraluminal filament, and then reperfused. Taurine (50 mg/kg) was administered intravenously 4 h, 8 h, 10 h, or 12 h after ischemia. The neurologic scores and the infarct volumes were evaluated 24 h after ischemia. Then, the effect of administration of taurine at 8 h after ischemia on the neutrophil infiltration in ischemic region was determined. Treatment with taurine 4 h or 8 h after ischemia significantly improved the neurologic function, and decreased the infarct volumes 24 h after ischemia. However, administration of taurine at 10 h or 12 h after ischemia had no significant neuroprotection. Further, taurine administered at 8 h after ischemia markedly reduced myeloperoxidase activity and attenuated neutrophil infiltration in ischemic region. Our data suggest that the therapeutic window of taurine against experimental stroke is of at least 8 h, and suppressing the neutrophil infiltration may be one of the mechanisms of delayed administration of taurine against experimental stroke.

Taurine protects against bilirubin-induced neurotoxicity in vitro

Kernicterus is a bilirubin-induced encephalopathy in newborn. Its spectrum ranges from subtle extrapyramidal to acute encephalopathy and chronic posticteric sequelae. Current treatment of this serious problem is far from optimal. Taurine has been documented to have protective effects on neuronal cells against ischemia in vivo and in vitro. This study used primary neuronal culture to investigate the toxicological effects of unconjugated bilirubin (UCB) and the protection of taurine against UCB-mediated neuron damage. Dose-dependent reduction of cell viability was found. Changes in neurite outgrowth preceded the reduction of cell viability. The bilirubin-mediated neurotoxicity is mainly due to increased rate of cell apoptosis and higher levels of intracellular free calcium ion level. Taurine dramatically improved cell viability in cultured neurons exposed to 12.5 µM UCB. Taurine pretreatment reduced UCB-mediated apoptotic cell death in primary cultured neurons in a concentration-dependent manner, which was associated with reversal of the increased intracellular free calcium ion levels caused by UCB. This study suggests the potential of taurine as a broad-spectrum agent for preventing and/or treating neuronal damage in neonatal jaundice.

Protection of taurine and granulocyte colony-stimulating factor against excitotoxicity induced by glutamate in primary cortical neurons

sBackgroundBoth taurine, an inhibitory neurotransmitter and granulocyte colony-stimulating factor (G-CSF), a growth factor, possess neuroprotective and neurotrophic properties in vitro. However, the mechanisms of their underlying neuroprotective effects are not fully understood.MethodsIn the present study, we investigated the potential protective benefits of taurine, G-CSF and the combination of taurine and G-CSF against excitotoxicity induced by glutamate in primary cortical neuronal cultures.Results25 mM taurine, 25 ng/ml G-CSF and the combination of 25 mM taurine and 25 ng/ml G-CSF showed a protective effect reaching 75%, 75% and 88%, respectively. Furthermore, taurine exerted its protective effect through down-regulation of expression of GRP 78, CHOP, Bim and caspase 12.ConclusionThe results showed that all of these treatments, taurine, G-CSF and the combination of taurine and G-CSF, protected primary cortical neurons against excitotoxicity induced by glutamate. ER stress is suppressed by taurine after glutamate toxicity.

Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress

BackgroundTaurine is a free amino acid present in high concentrations in a variety of organs of mammalians. As an antioxidant, taurine has been found to protect cells against oxidative stress, but the underlying mechanism is still unclear.MethodsIn this report, we present evidence to support the conclusion that taurine exerts a protective function against endoplasmic reticulum (ER) stress induced by H2O2 in PC 12 cells. Oxidative stress was introduced by exposure of PC 12 cells to 250 uM H2O2 for 4 hours.ResultsIt was found that the cell viability of PC 12 cells decreased with an increase of H2O2 concentration ranging from approximately 76% cell viability at 100 uM H2O2 down to 18% at 500 uM H2O2. At 250 uM H2O2, cell viability was restored to 80% by taurine at 25 mM. Furthermore, H2O2 treatment also caused a marked reduction in the expression of Bcl-2 while no significant change of Bax was observed. Treatment with taurine restored the reduced expression of Bcl-2 close to the control level without any obvious effect on Bax. Furthermore, taurine was also found to suppress up-regulation of GRP78, GADD153/CHOP and Bim induced by H2O2, suggesting that taurine may also exert a protective function against oxidative stress by reducing the ER stress.ConclusionIn summary, taurine was shown to protect PC12 cells against oxidative stress induced by H2O2. ER stress was induced by oxidative stress and can be suppressed by taurine.