Role of taurine in the central nervous system

Taurine demonstrates multiple cellular functions including a central role as a neurotransmitter, as a trophic factor in CNS development, in maintaining the structural integrity of the membrane, in regulating calcium transport and homeostasis, as an osmolyte, as a neuromodulator and as a neuroprotectant. The neurotransmitter properties of taurine are illustrated by its ability to elicit neuronal hyperpolarization, the presence of specific taurine synthesizing enzyme and receptors in the CNS and the presence of a taurine transporter system. Taurine exerts its neuroprotective functions against the glutamate induced excitotoxicity by reducing the glutamate-induced increase of intracellular calcium level, by shifting the ratio of Bcl-2 and Bad ratio in favor of cell survival and by reducing the ER stress. The presence of metabotropic taurine receptors which are negatively coupled to phospholipase C (PLC) signaling pathway through inhibitory G proteins is proposed, and the evidence supporting this notion is also presented

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

<p>Abstract</p> <p>Background</p> <p>Taurine 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.</p> <p>Methods</p> <p>In 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.</p> <p>Results</p> <p>It 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.</p> <p>Conclusion</p> <p>In 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.</p

Demonstration of functional coupling between dopamine synthesis and its packaging into synaptic vesicles

This is the publisher's version, also available electronically from "http://link.springer.com".We have previously shown that the membrane-associated form of the GABA-synthesizing enzyme, glutamate decarboxylase 65 (GAD65), is activated by synaptic vesicle proton gradient-mediated protein phosphorylation. We now report that the rate-limiting enzyme in dopamine (DA) biosynthesis, tyrosine hydroxylase (TH), is regulated similarly to GAD65. The membrane-associated form of TH (MTH) was activated by conditions favoring protein phosphorylation (e.g. ATP) and was inhibited by phosphatase (e.g. calf intestine phosphatase). Furthermore, the ATP-mediated activation of MTH was abolished by conditions that disrupted the proton gradient of synaptic vesicles, e.g. the presence of carbonyl cyanidem-chorophenylhydrazone, gramicidin, or the V-type ATPase inhibitor (bafilomycin), but not the P-type ATPase inhibitor (vanadate). Moreover, DA newly synthesized from tyrosine by MTH and membrane-associated aromatic amino acid decarboxylase was taken up preferentially rather than pre-existing DA. Therefore, the previously proposed model showing close coupling between GABA synthesis and GABA packaging into synaptic vesicles by vesicular GABA transporters is also applicable to the DA system. Hence, it is concluded that there is a general coupling mechanism between neurotransmitter synthesis and packaging of transmitter into synaptic vesicles

Mechanisms of Neuronal Protection against Excitotoxicity, Endoplasmic Reticulum Stress, and Mitochondrial Dysfunction in Stroke and Neurodegenerative Diseases

In stroke and neurodegenerative disease, neuronal excitotoxicity, caused by increased extracellular glutamate levels, is known to result in calcium overload and mitochondrial dysfunction. Mitochondrial deficits may involve a deficiency in energy supply as well as generation of high levels of oxidants which are key contributors to neuronal cell death through necrotic and apoptotic mechanisms. Excessive glutamate receptor stimulation also results in increased nitric oxide generation which can be detrimental to cells as nitric oxide interacts with superoxide to form the toxic molecule peroxynitrite. High level oxidant production elicits neuronal apoptosis through the actions of proapoptotic Bcl-2 family members resulting in mitochondrial permeability transition pore opening. In addition to apoptotic responses to severe stress, accumulation of misfolded proteins and high levels of oxidants can elicit endoplasmic reticulum (ER) stress pathways which may also contribute to induction of apoptosis. Two categories of therapeutics are discussed that impact major pro-death events that include induction of oxidants, calcium overload, and ER stress. The first category of therapeutic agent includes the amino acid taurine which prevents calcium overload and is also capable of preventing ER stress by inhibiting specific ER stress pathways. The second category involves N-methyl-D-aspartate receptor (NMDA receptor) partial antagonists illustrated by S-Methyl-N, N-diethyldithiocarbamate sulfoxide (DETC-MeSO), and memantine. DETC-MeSO is protective through preventing excitotoxicity and calcium overload and by blocking specific ER stress pathways. Another NMDA receptor partial antagonist is memantine which prevents excessive glutamate excitation but also remarkably allows maintenance of physiological neurotransmission. Targeting of these major sites of neuronal damage using pharmacological agents is discussed in terms of potential therapeutic approaches for neurological disorders

Areca Users in Combination with Tobacco and Alcohol Use Are Associated with Younger Age of Diagnosed Esophageal Cancer in Taiwanese Men

BACKGROUND: Whether the habitual use of substances (tobacco, alcohol, or areca nut (seed of the Areca palm)) can affect the age of esophageal squamous cell carcinoma (ESCC) presentation has rarely been examined. METHODS: The study subjects were those who were males and the first time to be diagnosed as ESCC (ICD-9 150) and who visited any of three medical centers in Taiwan between 2000 and 2009. A standardized questionnaire was used to collect substance uses and other variables. RESULTS: Mean age (±SD) at presentation of ESCC was 59.2 (±11.3) years in a total of 668 cases. After adjusting for other covariates, alcohol drinkers were 3.58 years younger to have ESCC than non-drinkers (p = 0.002). A similar result was found among areca chewers, who were 6.34 years younger to have ESCC than non-chewers (p<0.0001), but not among cigarette smokers (p = 0.10). When compared to the group using 0-1 substances, subjects using both cigarettes and alcohol were nearly 3 years younger to contract ESCC. Furthermore, those who use areca plus another substance were 7-8 years younger. Subjects using all three substances had the greatest age difference, 9.20 years younger (p<0.0001), compared to the comparison group. CONCLUSION: Our findings suggest that habitually consuming tobacco, alcohol, and areca nut can influence the age-onset of ESCC. Since the development of ESCC is insidious and life-threatening, our observation is worthy to be reconfirmed in the large-scale and long-term follow-up prospective cohort studies to recommend the screening strategy of this disease

A Vision-Based Driver Nighttime Assistance and Surveillance System Based on Intelligent Image Sensing Techniques and a Heterogamous Dual-Core Embedded System Architecture

This study proposes a vision-based intelligent nighttime driver assistance and surveillance system (VIDASS system) implemented by a set of embedded software components and modules, and integrates these modules to accomplish a component-based system framework on an embedded heterogamous dual-core platform. Therefore, this study develops and implements computer vision and sensing techniques of nighttime vehicle detection, collision warning determination, and traffic event recording. The proposed system processes the road-scene frames in front of the host car captured from CCD sensors mounted on the host vehicle. These vision-based sensing and processing technologies are integrated and implemented on an ARM-DSP heterogamous dual-core embedded platform. Peripheral devices, including image grabbing devices, communication modules, and other in-vehicle control devices, are also integrated to form an in-vehicle-embedded vision-based nighttime driver assistance and surveillance system

Development of biomaterial surfaces with and without microbial nanosegments

Infections by microorganisms are a major problem in public health throughout the world. Artificial materials, including biomedical goods, inherently lack defense against microbial development. Therefore, microbial cells can adhere on any type of artificial surface, particularly in a moist environment, and start to multiply to form a huge population. In this review, we will discuss a strategy for designing antimicrobial polymers and antimicrobial surfaces. Generally, there are five types of antimicrobial polymers: (a) polymeric biocides, (b) biocidal polymers, (c) biocide-releasing polymers, (d) bioactive oligopeptides, and (e) antimicrobial surfaces. Antimicrobial surfaces preventing the growth of microorganisms are a promising method to inhibit the spread of microbial infections. The antimicrobial surfaces can reject the attachment of microbes and/or kill microbes in the vicinity and can be designed to kill microbes on contact. It is recommended that the material surface not release biocidal substances, therefore preventing exhaustion of biocide release to kill microbes. Furthermore, the antimicrobial surfaces are desired to be nontoxic to human cells. The development of contact-active antimicrobial surfaces by grafting antimicrobial nanosegments onto the material surface will be an important topic in the future

Molecular Dynamics Simulation of Nanoindentation-induced Mechanical Deformation and Phase Transformation in Monocrystalline Silicon

This work presents the molecular dynamics approach toward mechanical deformation and phase transformation mechanisms of monocrystalline Si(100) subjected to nanoindentation. We demonstrate phase distributions during loading and unloading stages of both spherical and Berkovich nanoindentations. By searching the presence of the fifth neighboring atom within a non-bonding length, Si-III and Si-XII have been successfully distinguished from Si-I. Crystallinity of this mixed-phase was further identified by radial distribution functions

Problematic Internet Use in High School Students in Guangdong Province, China

BACKGROUND: Problematic Internet Use (PIU) is a growing problem in Chinese adolescents. There are many risk factors for PIU, which are found at school and at home. This study was designed to investigate the prevalence of PIU and to investigate the potential risk factors for PIU among high school students in China. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was conducted. A total of 14,296 high school students were surveyed in four cities in Guangdong province. Problematic Internet Use was assessed by the 20-item Young Internet Addiction Test (YIAT). Information was also collected on demographics, family and school-related factors and Internet usage patterns. Of the 14,296 students, 12,446 were Internet users. Of those, 12.2% (1,515) were identified as problematic Internet users (PIUs). Generalized mixed-model regression revealed that there was no gender difference between PIUs and non-PIUs. High study-related stress, having social friends, poor relations with teachers and students and conflictive family relationships were risk factors for PIU. Students who spent more time on-line were more likely to develop PIU. The habits of and purposes for Internet usage were diverse, influencing the susceptibility to PIU. CONCLUSIONS/SIGNIFICANCE: PIU is common among high school students, and risk factors are found at home and at school. Teachers and parents should pay close attention to these risk factors. Effective measures are needed to prevent the spread of this problem