Current Search:  Taurine -- Physiological effect (x)

View All Items

  • CSV Spreadsheet
(1 - 4 of 4)
New insights into the neuromodulatory role and potential action site of taurine in retinal neurons
Title
New insights into the neuromodulatory role and potential action site of taurine in retinal neurons.
Creator
Bulley, Simon, Charles E. Schmidt College of Science, Department of Biomedical Science
Abstract/Description
Taurine is the second most abundant amino acid in the CNS after glutamate and its functions have been found largely related to intracellular calcium ([Ca2+]i) modulation, osmoregulation, membrane stabilization, reproduction and immunity. The action of taurine has also been implicated in neurotransmission and neuromodulation though its specific sites of action are not fully understood. Isolated retinal neurons from the larval tiger salamanders (Ambystoma tigrinum) were used as a model to study...
Show moreTaurine is the second most abundant amino acid in the CNS after glutamate and its functions have been found largely related to intracellular calcium ([Ca2+]i) modulation, osmoregulation, membrane stabilization, reproduction and immunity. The action of taurine has also been implicated in neurotransmission and neuromodulation though its specific sites of action are not fully understood. Isolated retinal neurons from the larval tiger salamanders (Ambystoma tigrinum) were used as a model to study the neuromodulatory role of taurine in the CNS and to gain insights into its potential sites of action. A combination of techniques was used, including whole-cell patch clamp recording to study taurine's regulation of voltage-gated potassium (K+) and Ca2+ channels and Fluo-4AM Ca2+-imaging to study taurine's regulation of glutamate-induced [Ca2+] I,. Taurine was shown to suppress of glutamate-induced [Ca2+] l, in a dose dependent manner. This suppression was mostly sensitive to the glycine rece ptor antagonist Strychnine but insensitive to any GABA receptor antagonist. The remaining strychnine-insensitive effect was inhibited with the protein kinase A (PKA) inhibitor, PKI, suggesting that there was an additional metabotropic pathway. Moreover, using the protein kinase C (PKC) inhibitor, GF109203X, there was an enhancement in strychnine-insensitive taurine's regulation. Taurine inhibits voltage-gated Ca2+ channels in the retinal neurons and has a dual effect on voltage-gated K+ channels. Taurine causes an increase in K+ current amplitude which is further enhanced with PKI and blocked with GF109203X, suggesting that it is through a PKC-dependent pathway negatively controlled by PKA-dependent pathway., There is a suppression of K+ current by taurine with intracellular application of GF109203X, suggesting that the reduction is through a PKA-dependent pathway. With both PKC and PKA inhibitors there is no longer an enhancement in maximum amplitude but a shift of volt dependence on a hyperpolarizing direction. Taurine's enhancement of K+ current is blocked by the Kv1.3 subtype antagonist Margatoxin, with Kv1.3 accounting for the majority of delayed-rectifier sustained current in bipolar and amacrine cells, as well as 50% of ganglion cells. Interestingly, the enhancement of K+ current by taurine is blocked by 5HT2A antagonist MDL11939, suggesting that activation of PKC is through this metabotropic serotonin receptor subtype. The suppression of voltage-gated Ca2+ channels is reversed with a combination of MDL11939 and the 5HT1A antagonist NAN-190. These results provide the evidence that the natural effect of taurine in the retinal neurons might be dependent on the activation of both 5HT1A and 5HT2A receptors. The high apparent activity of taurine on 5HT receptors could have important implication for the actions of taurine in central brain in which taurine has been known to be beneficial for improving mental health, as well as learning and memory processes.
Show less
Date Issued
2010
PURL
http://purl.flvc.org/FAU/2953206
Subject Headings
Biological transport, Eye, Physiology, Taurine, Physiological effect, Taurine, Therapeutic use, Central nervous system, Physiology
Format
Document (PDF)
Mechanism of neuroprotection in stroke-related models
Title
Mechanism of neuroprotection in stroke-related models.
Creator
Pan, Chunliu., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Stroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three...
Show moreStroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three stroke-related models : hypoxia, excessive glutamtate and oxidative stress. In the first part of this dissertation, we studied the neuroprotection of taurine against oxidative stress induced by H2O2 in PC12 cells. Our results show that extracellular taurine exerts a neuroprotective function by restoring the expression of Bcl-2 and downregulation of the three Endoplasmic Reticulum (ER) stress markers : GRP78, Bim and CHOP/GADD153, suggesting that ER stress can be provoked by oxidative stress and can be suppressed by taurine. In the second part, glutamate excitotoxicity-induced ER stress was studied with dose and time as variables in primary cortical neurons. The results demonstrate that glutamate excitotoxicity leads to the activation of three ER stress pathways (PERK, ATF6 and IRE1) by initiating PERK first, ATF6 second and IRE1 pathway last. The third part of this dissertation studied the robust and beneficial protection of taurine in cortical neurons under hypoxia/reoxygenation or glutamate toxicity condition. We found that taurine suppresses the up-regulation of GRP778, Bim, caspase-12 and GADD153/CHOP induced by excessive glutamate or hypoxia/reoxygenation, suggesting that taurine may exert a protective function against hypoxia/regeneration by reducing the ER stress., Moreover, taurine can down-regulate the ratio of cleaved ATF6 and full length ATF6, and p-IRE1 expresssion, indicating that taurine inhibits the ER stress induced by hypoxia/reoxygenation or glutamate through suppressing ATF6 and IRE1 pathways. In the fourth part, the synergistic benefits of the combination of taurine and G-CSF, and the neuroprotective effects of G-CSF, sulindac or DETC-MeSO are studied in cortical neurons. Our results show that G-CSF, sulindac or DETC-MeSO can highly increase the neuron visibility by inhibiting ER stress induced by hypoxia/reoxygenation or glutamate toxicity. Furthermore, we proved that G-CSF or sulindac can significantly inhibit the activation of ATF6 or IRE1 pathway stimulated by hypoxia/reoxygenation, and DETC-MeSO can suppress the activation of both PERK and IRE1 pathways in primary neuron cultures. These findings provide promising and rational strategies for stroke therapy.
Show less
Date Issued
2012
PURL
http://purl.flvc.org/FAU/3352284
Subject Headings
Sulindac, Physiological effect, Taurine, Physiological effect, Cerebral ischemia, Prevention, Biochemical markers, Diagnostic use, Apoptosis, Oxidation reduction reaction
Format
Document (PDF)
Taurine inhibits glutamate-induced excitotoxicity through a calpain dependent pathway
Title
Taurine inhibits glutamate-induced excitotoxicity through a calpain dependent pathway.
Creator
Leon, Rebecca, Prentice, Howard, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Taurine, an endogenous ammo acid and neuromodulator, has been found to be neuroprotective against numerous forms of neurotoxicity including glutamate-induced excitotoxicity. Previously we have shown that taurine inhibits glutamate-induced calcium influx through VGCCs and NMDA receptors. Although the neuroprotective effects of taurine against excitotoxicity have been attributed to its intracellular Ca2+ regulatory functions, the complete mechanism underling taurine neuroprotection has remained...
Show moreTaurine, an endogenous ammo acid and neuromodulator, has been found to be neuroprotective against numerous forms of neurotoxicity including glutamate-induced excitotoxicity. Previously we have shown that taurine inhibits glutamate-induced calcium influx through VGCCs and NMDA receptors. Although the neuroprotective effects of taurine against excitotoxicity have been attributed to its intracellular Ca2+ regulatory functions, the complete mechanism underling taurine neuroprotection has remained unclear. Using primary rat cortical neuronal cell cultures, we have determined key cytosolic components to the mechanism of taurine neuroprotection. In this study we have found that taurine inhibits excitotoxicity by suppressing glutamate-induced elevations in [Ca2+]i, preventing calpain activation, and inhibiting reductions in Bel- 2:Bax ratios and consequently activation of the intrinsic pathway.
Show less
Date Issued
2008
PURL
http://purl.flvc.org/fau/fd/FA00000788
Subject Headings
Cellular signal transduction, Taurine--Physiological effect, Proteolytic enzymes--Research
Format
Document (PDF)
Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress
Title
Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress.
Creator
Pan, Chunliu, Giraldo, Grace S., Prentice, Howard, Wu, Jang-Yen
Date Issued
2010-08-24
PURL
http://purl.flvc.org/fcla/dt/3327276
Subject Headings
Oxidative Stress, Oxidative Stress --drug effects, Oxidative Stress --physiology, Antioxidants --pharmacology, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-bcl-2, PC12 Cells --drug effects, Endoplasmic Reticulum --drug effects, Transcription Factor CHOP, Taurine
Format
Document (PDF)