Loss Of Taurine Research Articles

Taurine linked with healthy aging.

Reversing age-associated taurine loss improves mouse longevity and monkey health.

Impact of Sea Warming and 17-α-Ethinylestradiol Exposure on the Lipid Metabolism of Ruditapes philippinarum Clams.

This paper reports on an NMR metabolomics study of lipophilic extracts of Ruditapes philippinarum clams exposed to the hormonal contaminant 17-α-ethinylestradiol (EE2), at 17 °C and 21 °C. The results reveal that exposure at 17 °C triggers a weak response at low EE2 concentrations, suggestive of a slight increase in membrane rigidity, followed by lipid metabolic stability at higher EE2 concentrations. On the other hand, at 21 °C, lipid metabolism begins to respond at 125 ng/L EE2, with antioxidant docosahexaenoic acid (DHA) helping to tackle high-oxidative-stress conditions, in tandem with enhanced storage of triglycerides. Exposure to 625 ng/L EE2 (highest concentration) enhances phosphatidylcholine (PtdCho) and polyunsaturated fatty acid (PUFA) levels, their direct intercorrelation suggesting PUFA incorporation in new membrane phospholipids. This should lead to increased membrane fluidity, probably aided by a decrease in cholesterol. PUFA levels, considered a measure of membrane fluidity, were strongly (and positively) correlated to intracellular glycine levels, thus identifying glycine as the main osmolyte entering the cells under high stress. Membrane fluidity also seems to elicit the loss of taurine. This work contributes to the understanding of the mechanisms of response of R. philippinarum clams to EE2 in tandem with warming while unveiling novel potential markers of stress mitigation, namely high levels of PtdCho, PUFAs (or PtdCho/glycerophosphocholine and PtdCho/acetylcholine ratios) and linoleic acid and low PUFA/glycine ratios.

Plasma and Whole Blood Taurine Concentrations in Dogs May Not Be Sensitive Indicators of Taurine Deficiency When Dietary Sulfur Amino Acid Content Is Reduced

BackgroundTaurine status is impacted by dietary supply of methionine and cysteine (SAA) and possibly intestinal microbial activity, where plasma and whole blood taurine concentrations are currently used to evaluate taurine status.ObjectiveWe determined effects of dietary SAA restriction on rate and extent of taurine depletion of blood and skeletal muscle in dogs of two body sizes, and whether oral antibiotic administration affected the taurine depletion and fecal bile acid excretion of the dogs.MethodsAdult, male, Beagles (n = 6; 10.1–13.1 kg) and larger mixed-breed dogs (n = 6; 28.5–41.1 kg) were given four dry-expanded diets, whereby each successive diet contained lower protein and/or SAA concentration. After receiving the final diet for 44 weeks, all dogs were orally administered a mixture of ampicillin, neomycin sulfate, and metronidazole for 12 weeks. Taurine concentrations were determined every 2–4 weeks in venous blood and voided urine and every 4 to 16 weeks in biopsied semimembranosus muscle. Fecal bile acid excretion before and after antibiotics administration were quantified.ResultsWhen given for 36 weeks the lowest SAA diet, 3.4% methionine and 2.9% cystine, taurine concentrations in whole blood were not different between groups, while taurine in plasma declined (P < 0.05) in large but not in small dogs, and taurine in biopsied muscle decreased (P < 0.05) by 50% in large and by 37% in small dogs. Concentrations of taurine in muscle were lower (P < 0.01) and fecal bile acids greater (P = 0.001) in large than small dogs. Antibiotic administration restored plasma and muscle taurine to initial concentrations and halved fecal bile acid excretion by dogs of both groups.ConclusionsBlood taurine concentration may not be a sensitive indictor of taurine depletion caused by low intake of bioavailable SAA in dogs, especially in large dogs. Taurine status and dietary SAA requirements of dogs may substantively depend on taurine loss mediated by intestinal microbiota.

A longitudinal multimodal in vivo molecular imaging study of the 3xTg-AD mouse model shows progressive early hippocampal and taurine loss.

The understanding of the natural history of Alzheimer’s disease (AD) and temporal trajectories of in vivo molecular mechanisms requires longitudinal approaches. A behavioral and multimodal imaging study was performed at 4/8/12 and 16 months of age in a triple transgenic mouse model of AD (3xTg-AD). Behavioral assessment included the open field and novel object recognition tests. Molecular characterization evaluated hippocampal levels of amyloid β (Aβ) and hyperphosphorylated tau. Magnetic resonance imaging (MRI) included assessment of hippocampal structural integrity, blood–brain barrier (BBB) permeability and neurospectroscopy to determine levels of the endogenous neuroprotector taurine. Longitudinal brain amyloid accumulation was assessed using 11C Pittsburgh compound B positron emission tomography (PET), and neuroinflammation/microglia activation was investigated using 11C-PK1195. We found altered locomotor activity at months 4/8 and 16 months and recognition memory impairment at all time points. Substantial early reduction of hippocampal volume started at month 4 and progressed over 8/12 and 16 months. Hippocampal taurine levels were significantly decreased in the hippocampus at months 4/8 and 16. No differences were found for amyloid and neuroinflammation with PET, and BBB was disrupted only at month 16. In summary, 3xTg-AD mice showed exploratory and recognition memory impairments, early hippocampal structural loss, increased Aβ and hyperphosphorylated tau and decreased levels of taurine. In sum, the 3xTg-AD animal model mimics pathological and neurobehavioral features of AD, with early-onset recognition memory loss and MRI-documented hippocampal damage. The early-onset profile suggests temporal windows and opportunities for therapeutic intervention, targeting endogenous neuroprotectors such as taurine.

Role of Taurine in Cellular Volume Regulation in Erythrocytes of Air-Breathing Catfish (Clarias magur) Under Osmotic Stress

The present study investigated the role of taurine in cellular volume regulation of erythrocytes isolated from freshwater air-breathing magur catfish (Clarias magur) under osmotic stress. Exposure of erythrocytes, pre-loaded with or without taurine, to hypotonic medium (− 80 mOsmol/L) led to a significant decrease in taurine level in the erythrocytes due to efflux of taurine through a band 3 transporter protein present in the plasma membrane with a slight increase in cellular volume of erythrocytes by 12–13%, whereas incubation of erythrocytes with hypertonic medium (+ 80 mOsmol/L) with taurine caused a significant uptake of taurine by the erythrocytes through the Na+-dependent pathway but without any loss of taurine from the erythrocytes which was accompanied by a slight decrease in the cellular volume of erythrocytes by 11–12%. Furthermore, a direct correlation between the osmosensitive cellular volume and taurine release could be established in the erythrocytes of magur catfish under hypotonic stress (r = 0.9921). In conclusion, the erythrocytes of air-breathing magur catfish do possess a very efficient taurine-dependent volume regulatory mechanism to resist the changes in cellular volume under anisotonic conditions as a unique adaptational strategy to defend against the osmosensitive changes in cellular volume of erythrocytes.

Pathway Analysis of a Transcriptome and Metabolite Profile to Elucidate a Compensatory Mechanism for Taurine Deficiency in the Heart of Taurine Transporter Knockout Mice

Taurine, which is abundant in mammalian tissues, especially in the heart, is essential for cellular osmoregulation. We previously reported that taurine deficiency leads to changes in the levels of several metabolites, suggesting that alterations in those metabolites might compensate in part for tissue taurine loss, a process that would be important in maintaining cardiac homeostasis. In this study, we investigated the molecular basis for changes in the metabolite profile of a taurine-deficient heart using pathway analysis based on the transcriptome and metabolome profile in the hearts of taurine transporter knockout mice (TauTKO mice), which have been reported by us. First, the genes associated with transport activity, such as the solute carrier (SLC) family, are increased in TauTKO mice, while the established transporters for metabolites that are elevated in the TauTKO heart, such as betaine and carnitine, are not altered by taurine deficiency. Second, the integrated analysis using transcriptome and metabolome data revealed significant increases and/or decreases in the genes involved in Arginine metabolism, Ketone body degradation, Glycerophospholipid metabolism, and Fatty acid metabolism in the KEGG pathway database. In conclusion, these pathway analyses revealed genetic compensatory mechanisms involved in the control of the metabolome profile of the taurine-deficient heart.

Imaging Taurine in the Central Nervous System Using Chemically Specific X-ray Fluorescence Imaging at the Sulfur K-Edge.

A method to image taurine distributions within the central nervous system and other organs has long been sought. Since taurine is small and mobile, it cannot be chemically "tagged" and imaged using conventional immuno-histochemistry methods. Combining numerous indirect measurements, taurine is known to play critical roles in brain function during health and disease and is proposed to act as a neuro-osmolyte, neuro-modulator, and possibly a neuro-transmitter. Elucidation of taurine's neurochemical roles and importance would be substantially enhanced by a direct method to visualize alterations, due to physiological and pathological events in the brain, in the local concentration of taurine at or near cellular spatial resolution in vivo or in situ in tissue sections. We thus have developed chemically specific X-ray fluorescence imaging (XFI) at the sulfur K-edge to image the sulfonate group in taurine in situ in ex vivo tissue sections. To our knowledge, this represents the first undistorted imaging of taurine distribution in brain at 20 μm resolution. We report quantitative technique validation by imaging taurine in the cerebellum and hippocampus regions of the rat brain. Further, we apply the technique to image taurine loss from the vulnerable CA1 (cornus ammonis 1) sector of the rat hippocampus following global brain ischemia. The location-specific loss of taurine from CA1 but not CA3 neurons following ischemia reveals osmotic stress may be a key factor in delayed neurodegeneration after a cerebral ischemic insult and highlights the significant potential of chemically specific XFI to study the role of taurine in brain disease.

Assessment of the in vitro barrier integrity by in vitro TEER measurement for toxicology screening

Cod is a relatively new species in intensive aquaculture. The aim of this study was to compare the nutritional composition and bioactive properties of wild and farmed cod as well as investigate how cooking influenced these parameters. Wild cod contained significantly more docosahexaenoic acid, whereas the levels of linoleic acid, eicosapentaenoic acid, and docosapentaenoic acid were lower than in farmed cod. Only minor difference in amino acid profile were found between wild and farmed cod but protein content was higher in the latter. Baking resulted in lower loss of moisture and a corresponding lower loss of taurine compared to poaching. The angiotensin converting enzyme (ACE) inhibitory capacity did not differ between wild and farmed cod (IC50 values of 0.06 mg/mL) nor was it significantly affected by cooking. From this study, it is evident that intake of wild and farmed cod provides similar health-promoting effects that are maintained during cooking.

A novel approach to introduce nutrients into the fish egg; the effect of egg taurine on first feeding gilthead sea bream (Sparus aurata) performance

A potential key ingredient in broodstock and larval nutrition is the beta amino sulfonic acid; taurine. In the present study we investigated a novel application of electroporation-based methodology to introduce nutrients, such as taurine, into fertilized fish eggs with the aim of improving larval performance. In calibration trials, batches of 60 fertilized gilthead sea bream (Sparus aurata) eggs were electroporated in order to evaluate various combinations of voltage (V), time interval (ms) and pulse number. These resulted in egg hatchability and larval survival 24h later that were not significantly (P>0.05) different from the non-electroporated controls. The chosen electroporation protocol demonstrated a more permeable egg membrane by the significantly (P<0.001) higher proportion of eggs incorporating a fluorescein marker in the yolk sac compared to the controls. The selected protocol was used to taurine enrich sea bream eggs in order to determine the effect of taurine level in pre- and exogenous feeding larvae.The taurine content of the taurine electroporated eggs was 6.2× higher (P<0.05) than the control eggs (4.36±2.24 and 0.7±0.02mgg−1 DW, respectively). On the other hand, the taurine level dropped considerably after hatching but was still significantly higher than the control pre-larvae (1.11±0.07 and 0.87±0.04mgg−1 DW, respectively) while the taurine levels in the control and treatment 10days post hatch (dph) larvae were not significantly (P>0.05) different. Taurine treated eggs exhibited a significantly (P<0.01) lower incidence of urinary calculi at 4, 6, 8 and 10dph and a lower frequency (P<0.01) of the larger (>50μm) calculi. Moreover, the control larvae ingested less rotifers, which was significant (P<0.05) at 4dph, than the taurine larvae. Interestingly, larvae from either the control or taurine treatment having large calculi ingested significantly (P<0.01) less rotifers. These results suggest a correlation between the presence of large calculi and reduced prey hunting success. However taurine enrichment of eggs did not promote growth by 10dph larvae suggesting that this technique should be modified to reduce taurine loss at hatching and/or that taurine live food enrichment is also necessary in order to maintain the level of this critical nutrient in early stage larvae. Nevertheless, the present study demonstrated the potential of electroporation as a novel high throughput approach to introduce taurine and/or other critical nutrients into the developing eggs and a potential alternative to costly broodstock dietary supplementation. Statement of relevance to the field of commercial aquaculturePotential alternative to broodstock dietary supplementation.

Intracellular levels of glutamate in swollen astrocytes are preserved via neurotransmitter reuptake and de novo synthesis: implications for hyponatremia.

Hyponatremia and several other CNS pathologies are associated with substantial astrocytic swelling. To counteract cell swelling, astrocytes lose intracellular osmolytes, including l-glutamate and taurine, through volume-regulated anion channel. In vitro, when swollen by exposure to hypo-osmotic medium, astrocytes lose endogenous taurine faster, paradoxically, than l-glutamate or l-aspartate. Here, we explored the mechanisms responsible for differences between the rates of osmolyte release in primary rat astrocyte cultures. In radiotracer assays, hypo-osmotic efflux of preloaded [(14) C]taurine was indistinguishable from d-[(3) H]aspartate and only 30-40% faster than l-[(3) H]glutamate. However, when we used HPLC to measure the endogenous intracellular amino acid content, hypo-osmotic loss of taurine was approximatelyfivefold greater than l-glutamate, and no loss of l-aspartate was detected. The dramatic difference between loss of endogenous taurine and glutamate was eliminated after inhibition of both glutamate reuptake [with 300μM dl-threo-β-benzyloxyaspartic acid (TBOA)] and glutamate synthesis by aminotransferases [with 1mM aminooxyacetic acid (AOA)]. Treatment with TBOA+AOA made reductions in the intracellular taurine and l-glutamate levels approximately equal. Taken together, these data suggest that swollen astrocytes actively conserve intracellular glutamate via reuptake and de novo synthesis. Our findings likely also explain why in animal models of acute hyponatremia, extracellular levels of taurine are dramatically elevated with minimal impact on extracellular l-glutamate. We identified mechanisms that allow astrocytes to conserve intracellular l-glutamate (Glu) upon exposure to hypo-osmotic environment. Cell swelling activates volume-regulated anion channel (VRAC) and triggers loss of Glu, taurine (Tau), and other cytosolic amino acids. Glu is conserved via reuptake by Na(+) -dependent transporters and de novo synthesis in the reactions of mitochondrial transamination (TA). These findings explain why, in acute hyponatremia, extracellular levels of Tau can be dramatically elevated with minimal changes in extracellular Glu.

MTOR ensures increased release and reduced uptake of the organic osmolyte taurine under hypoosmotic conditions in mouse fibroblasts

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that modulates translation in response to growth factors and alterations in nutrient availability following hypoxia and DNA damage. Here we demonstrate that mTOR activity in Ehrlich Lettré ascites (ELA) cells is transiently increased within minutes following osmotic cell swelling and that inhibition of phosphatidylinositol-3-phosphatase (PTEN) counteracts the upstream phosphatidylinositol kinase and potentiates mTOR activity. PTEN inhibition concomitantly potentiates swelling-induced taurine release via the volume-sensitive transporter for organic osmolytes and anion channels (VSOAC) and enhances swelling-induced inhibition of taurine uptake via the taurine-specific transporter (TauT). Chronic osmotic stress, i.e., exposure to hypotonic or hypertonic media for 24 h, reduces and increases mTOR activity in ELA cells, respectively. Using rapamycin, we demonstrate that mTOR inhibition is accompanied by reduction in TauT activity and increase in VSOAC activity in cells expressing high (NIH3T3 fibroblasts) or low (ELA) amounts of mTOR protein. The effect of mTOR inhibition on TauT activity reflects reduced TauT mRNA, TauT protein abundance, and an overall reduction in protein synthesis, whereas the effect on VSOAC is mimicked by catalase inhibition and correlates with reduced catalase mRNA abundance. Hence, mTOR activity favors loss of taurine following hypoosmotic cell swelling, i.e., release via VSOAC and uptake via TauT during acute hypotonic exposure is potentiated and reduced, respectively, by phosphorylation involving mTOR and/or the kinases upstream to mTOR. Decrease in TauT activity during chronic hypotonic exposure, on the other hand, involves reduction in expression/activity of TauT and enzymes in antioxidative defense.

Leaching of taurine from commercial type aquaculture feeds

Leaching of soluble compounds from pelleted feeds is an issue for the aquaculture industry through increased environmental impact and reduced ingestion essential components. This study was undertaken to examine the leaching rates of taurine, a non-protein amino acid with critical physiological roles in teleosts. To this end we adapted a new liquid chromatography mass spectrometry (LC-MS) method for quantifying taurine. Twelve different feeds (4 mm dia.) varying in protein source and taurine levels were examined. Fishmeal content ranged from 0.0% to 45.5% with taurine supplementation ranging from 0.0% to 5.0%. Taurine was extracted and quantified from individual pellets in triplicate at six time points (0, 1, 5, 10, 20 and 40 min). Leaching rates ranged from 0.026 ± 0.005 to 0.826 ± 0.121 mg min−1 over 40 min at 27°C and were strongly correlated to initial taurine content of the feeds (for distilled water n = 12, P < 0.001, R2 = 0.91 for artificial seawater, 25 ppt, n = 4, P = 0.020, R2 = 0.96). Loss of taurine from feeds was 59.5 ± 16.5% after 40 min. This study shows that a significant amount of taurine is lost over time from uneaten feed and that taurine supplementation should exceed requirement levels for slow consumers or feed being delivered as multiple additions.

Nutritional content and bioactive properties of wild and farmed cod (Gadus morhua L.) subjected to food preparation

Cod is a relatively new species in intensive aquaculture. The aim of this study was to compare the nutritional composition and bioactive properties of wild and farmed cod as well as investigate how cooking influenced these parameters. Wild cod contained significantly more docosahexaenoic acid, whereas the levels of linoleic acid, eicosapentaenoic acid, and docosapentaenoic acid were lower than in farmed cod. Only minor difference in amino acid profile were found between wild and farmed cod but protein content was higher in the latter. Baking resulted in lower loss of moisture and a corresponding lower loss of taurine compared to poaching. The angiotensin converting enzyme (ACE) inhibitory capacity did not differ between wild and farmed cod (IC50 values of 0.06mg/mL) nor was it significantly affected by cooking. From this study, it is evident that intake of wild and farmed cod provides similar health-promoting effects that are maintained during cooking.

Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase

Pathophysiological conditions challenge cell volume homeostasis and perturb cell volume regulatory mechanisms leading to alterations of cell metabolism, active transepithelial transport, cell migration, and death. We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT₁) with the antiasthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium-sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (butylated hydroxytoluene, N-acetyl cysteine) and potentiated by H₂O₂. Ca²⁺ mobilization with ionomycin or ATP stimulates the swelling-induced taurine release whereas calmodulin inhibition (W7) inhibits the release. Chelation of the extracellular Ca²⁺ (EGTA) had no effect on swelling-induced taurine release but prevented ATP-induced stimulation. H₂O₂, ATP, and ionomycin were unable to stimulate the taurine release in the presence of AA861 or Zafirlukast, placing 5-LO and CysLT₁ as essential elements in the swelling-induced activation of VSOAC with ROS and Ca²⁺ as potent modulators. Inhibition of tyrosine kinases (genistein, cucurbitacin) reduces volume-sensitive taurine release, adding tyrosine kinases (Janus kinase) as regulators of VSOAC activity. Caspase-3 activity during hypoxia is unaffected by inhibition of 5-LO/CysLT₁ but reduced when swelling-induced taurine loss via VSOAC is prevented by DIDS excess extracellular taurine, indicating a beneficial role of taurine under hypoxia.

Effect of taurine on ischemia–reperfusion injury

Taurine is an abundant β-amino acid that regulates several events that dramatically influence the development of ischemia-reperfusion injury. One of these events is the extrusion of taurine and Na+ from the cell via the taurine/Na+ symport. The loss of Na+ during the ischemia-reperfusion insult limits the amount of available Na+ for Na+/Ca2+ exchange, an important process in the development of Ca2+ overload and the activation of the mitochondrial permeability transition, a key process in ischemia-reperfusion mediated cell death. Taurine also prevents excessive generation of reactive oxygen species by the respiratory chain, an event that also limits the activation of the MPT. Because taurine is an osmoregulator, changes in taurine concentration trigger "osmotic preconditioning," a process that activates an Akt-dependent cytoprotective signaling pathway that inhibits MPT pore formation. These effects of taurine have clinical implications, as experimental evidence reveals potential promise of taurine therapy in preventing cardiac damage during bypass surgery, heart transplantation and myocardial infarction. Moreover, severe loss of taurine from the heart during an ischemia-reperfusion insult may increase the risk of ventricular remodeling and development of heart failure.

Regulation of taurine homeostasis by protein kinase CK2 in mouse fibroblasts

Increased expression of the ubiquitous serine/threonine protein kinase CK2 has been associated with increased proliferative capacity and increased resistance towards apoptosis. Taurine is the primary organic osmolyte involved in cell volume control in mammalian cells, and shift in cell volume is a critical step in cell proliferation, differentiation and induction of apoptosis. In the present study, we use mouse NIH3T3 fibroblasts and Ehrlich Lettré ascites tumour cells with different CK2 expression levels. Taurine uptake via the Na(+) dependent transporter TauT and taurine release are increased and reduced, respectively, following pharmacological CK2 inhibition. The effect of CK2 inhibition on TauT involves modulation of transport kinetics, whereas the effect on the taurine release pathway involves reduction in the open-probability of the efflux pathway. Stimulation of PLA(2) activity, exposure to exogenous reactive oxygen species as well as inhibition of protein tyrosine phosphotases (PTP) potentiate the swelling-induced taurine loss. Inhibition of PI3K and PTEN reduces and potentiates swelling-induced taurine release, respectively. Inhibition of CK2 has no effect on PLA(2) activity and ROS production by NADPH oxidase, whereas it lifts the effect of PTEN and PTP inhibition. It is suggested that CK2 regulates the taurine release downstream to known swelling-induced signal transducers including PLA(2), NADPH oxidase and PI3K.

Impact of processing on the taurine content in processed seafood and their corresponding unprocessed raw materials

Processing of foods can lead to losses of water-soluble components, and some of these may have beneficial health effects. Taurine has lately attracted attention due to its suggested strong contribution to the health-promoting effects of seafood. The lack of systematic information on the content of conditionally essential nutrients, such as taurine, has led to this study. The taurine concentrations in a variety of common marine dinners and spreads, and their corresponding raw materials, have been determined. Losses of taurine in processed products ranged up to 100% when compared with the taurine content of freshly caught specimens. Products soaked in brines or products subjected to rough processing conditions such as mincing and washing had greater loss compared with products with more intact muscle. Levels of taurine in processed seafood vary according to product type and brand, showing a potential for the industry to take measures in preventing losses of taurine and other water-soluble components.

Purinergic activation of anion conductance and osmolyte efflux in cultured rat hippocampal neurons

The majority of mammalian cells demonstrate regulatory volume decrease (RVD) following swelling caused by hyposmotic exposure. A critical signal initiating RVD is activation of nucleotide receptors by ATP. Elevated extracellular ATP in response to cytotoxic cell swelling during pathological conditions also may initiate loss of taurine and other intracellular osmolytes via anion channels. This study characterizes neuronal ATP-activated anion current and explores its role in net loss of amino acid osmolytes. To isolate anion currents, we used CsCl as the major electrolyte in patch electrode and bath solutions and blocked residual cation currents with NiCl(2) and tetraethylammonium. Anion currents were activated by extracellular ATP with a K(m) of 70 microM and increased over fourfold during several minutes of ATP exposure, reaching a maximum after 9.0 min (SD 4.2). The currents were blocked by inhibitors of nucleotide receptors and volume-regulated anion channels (VRAC). Currents showed outward rectification and inactivation at highly depolarizing membrane potentials, characteristics of swelling-activated anion currents. P2X agonists failed to activate the anion current, and an inhibitor of P2X receptors did not block the effect of ATP. Furthermore, current activation was observed with extracellular ADP and 2-(methylthio)adenosine 5'-diphosphate, a P2Y(1) receptor-specific agonist. Much less current activation was observed with extracellular UTP, suggesting the response is mediated predominantly by P2Y(1) receptors. ATP caused a dose-dependent loss of taurine and alanine that could be blocked by inhibitors of VRAC. ATP did not inhibit the taurine uptake transporter. Thus extracellular ATP triggers a loss of intracellular organic osmolytes via activation of anion channels. This mechanism may facilitate neuronal volume homeostasis during cytotoxic edema.

Evaluation of changes in nutrient composition during production of cross-linked protein microencapsulated diets for marine fish larvae and suspension feeders

Cross-linked protein capsules as a vehicle for delivery of nutrients to marine fish larvae and marine suspension feeders were investigated. The effects of the production process on both qualitative and quantitative changes in protein, lipid and micronutrient concentrations were evaluated. There were no changes in lipid concentration and only minor (but significant) differences in crude protein concentrations as a result of the encapsulation process. However, there was nearly a complete loss of water-soluble nitrogen during capsule production — almost 100% of the water-soluble protein was cross-linked and made insoluble and 79% of the TCA-soluble N was lost. Peptides and free amino acids were lost during the capsule washing stages, but except for a 100% loss of taurine, small changes in the amino acid profile were observed. There was more than 90% loss of water-soluble micronutrients such as thiamin, vitamin C and zinc during capsule production, and only minor increase in concentration of thiamin and zinc in the diet by increasing the levels of these minerals and vitamins were possible. The fat-soluble vitamin E was not affected by the production process and can be delivered at controlled concentrations, but vitamin A had loss ranging from 4–57% with increased inclusion of vitamin A. With the existing production protocol, the results suggest that cross-linked protein capsules are not suitable for the delivery of water-soluble nutrients to fish larvae and marine suspension feeders.

GABAA‐receptor modification in taurine transporter knockout mice causes striatal disinhibition

The Striatum is involved in the regulation of movements and motor skills. We have shown previously, that the osmolyte and neuromodulator taurine plays a role in striatal plasticity. We demonstrate now that hereditary taurine deficiency in taurine-transporter knock-out (TAUT KO) mice results in disinhibition of striatal network activity, which can be corrected by taurine supplementation. Modification of GABAA but not glycine receptors (taurine is a ligand for both receptor types) underlies this disinhibition. Whole-cell recordings from acutely isolated as well as cultured striatal neurons revealed a decreased agonist sensitivity of the GABAA receptor in TAUT KO neurons in the absence of changes in the maximal GABA-evoked current amplitude. The striatal GABA level in TAUT KO mice was unchanged. The amplitude enhancement of spontaneous IPSCs by zolpidem was stronger in TAUT KO than in wild-type (WT) animals. Tonic inhibition was absent in striatal neurons under control conditions but was detected after incubation with the GABA-transaminase inhibitor vigabatrin: bicuculline induced a larger shift of baseline current in WT as compared to TAUT KO neurons. Lack of taurine leads to reduced sensitivity of synaptic and extrasynaptic GABAA receptors and consequently to disinhibition. These findings help in understanding neuropathologies accompanied by the loss of endogenous taurine, for instance in hepatic encephalopathy.