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Mechanism of taurine as a neuroprotector

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Date Issued:
2005
Summary:
Taurine is one of the most abundant amino acids in mammals and several functions of taurine have been reported. One important function of taurine is its neuroprotection against the glutamate-induced neuronal damage. It was shown that the glutamate-induced neurotoxicity is caused by overexcitation of glutamate receptors and intracellular calcium, [Ca2+]i, elevation. In this dissertation, the mechanism underlying the action of taurine as a neuroprotector was investigated. It was found that taurine protected neurons against glutamate or Bay K 8644-induced neurotoxicity only at the concentration that inhibits the calcium influx induced by those two compounds. Furthermore, taurine couldn't protect neurons against sodium nitroprusside, a NO free radical donor, induced neurotoxicity. These results indicate that taurine exerts its neuroprotection by reducing the glutamate-induced [Ca2+]i elevation. Besides necrosis, apoptosis is another major way that glutamate induces neuronal cell death. The effect of taurine on the glutamate-induced apoptosis was investigated. It was found that taurine prevented the glutamate-induced DNA fragmentation, indicating taurine prevents the glutamate-induced apoptosis. We found that anti-apoptotic proteins (BCL-2 and BCL-X) were down-regulated by glutamate treatment and this down-regulation was prevented by taurine. No difference in pro-apoptotic proteins (BAX and BAD) was found. It was found that the down-regulation of BCL-2 and BCL-X was through calpain-mediated proteolysis, and taurine may exert its anti-apoptotic function by preventing the activation of calpain, which is due to the prevention of [Ca2+]i elevation. Furthermore, it was found that pre-treatment with taurine inhibited the glutamate-induced calcium influx through L-, P/Q-, N-type voltage-gated calcium channels and NMDA receptor. Surprisingly, taurine had no effect on calcium influx through the NMDA receptor when neurons were treated with NMDA in Mg 2+-free medium. The effect of taurine is unlikely through GABA A, or glycine receptors, since bicuculline and picrotoxin (GABA A receptor antagonists), and strychnine (glycine receptor antagonist), failed to block taurine's inhibitory effect on the glutamate-induced calcium influx. Since taurine was found to prevent the glutamate-induced membrane depolarization, we propose that taurine protects neurons against the glutamate excitotoxicity by preventing the glutamate-induced membrane depolarization, probably through the opening of chloride channels, therefore preventing the glutamate-induced calcium influx and the downstream events.
Title: Mechanism of taurine as a neuroprotector.
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Name(s): Wu, Heng
Florida Atlantic University, Degree Grantor
Charles E. Schmidt College of Science
Center for Complex Systems and Brain Sciences
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Issuance: monographic
Date Issued: 2005
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 161 p.
Language(s): English
Summary: Taurine is one of the most abundant amino acids in mammals and several functions of taurine have been reported. One important function of taurine is its neuroprotection against the glutamate-induced neuronal damage. It was shown that the glutamate-induced neurotoxicity is caused by overexcitation of glutamate receptors and intracellular calcium, [Ca2+]i, elevation. In this dissertation, the mechanism underlying the action of taurine as a neuroprotector was investigated. It was found that taurine protected neurons against glutamate or Bay K 8644-induced neurotoxicity only at the concentration that inhibits the calcium influx induced by those two compounds. Furthermore, taurine couldn't protect neurons against sodium nitroprusside, a NO free radical donor, induced neurotoxicity. These results indicate that taurine exerts its neuroprotection by reducing the glutamate-induced [Ca2+]i elevation. Besides necrosis, apoptosis is another major way that glutamate induces neuronal cell death. The effect of taurine on the glutamate-induced apoptosis was investigated. It was found that taurine prevented the glutamate-induced DNA fragmentation, indicating taurine prevents the glutamate-induced apoptosis. We found that anti-apoptotic proteins (BCL-2 and BCL-X) were down-regulated by glutamate treatment and this down-regulation was prevented by taurine. No difference in pro-apoptotic proteins (BAX and BAD) was found. It was found that the down-regulation of BCL-2 and BCL-X was through calpain-mediated proteolysis, and taurine may exert its anti-apoptotic function by preventing the activation of calpain, which is due to the prevention of [Ca2+]i elevation. Furthermore, it was found that pre-treatment with taurine inhibited the glutamate-induced calcium influx through L-, P/Q-, N-type voltage-gated calcium channels and NMDA receptor. Surprisingly, taurine had no effect on calcium influx through the NMDA receptor when neurons were treated with NMDA in Mg 2+-free medium. The effect of taurine is unlikely through GABA A, or glycine receptors, since bicuculline and picrotoxin (GABA A receptor antagonists), and strychnine (glycine receptor antagonist), failed to block taurine's inhibitory effect on the glutamate-induced calcium influx. Since taurine was found to prevent the glutamate-induced membrane depolarization, we propose that taurine protects neurons against the glutamate excitotoxicity by preventing the glutamate-induced membrane depolarization, probably through the opening of chloride channels, therefore preventing the glutamate-induced calcium influx and the downstream events.
Identifier: 9780542391606 (isbn), 12183 (digitool), FADT12183 (IID), fau:9090 (fedora)
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Adviser: Jang-Yen Wu.
Thesis (Ph.D.)--Florida Atlantic University, 2005.
Subject(s): Biology, Neuroscience
Held by: Florida Atlantic University Libraries
Persistent Link to This Record: http://purl.flvc.org/fcla/dt/12183
Sublocation: Digital Library
Use and Reproduction: Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Use and Reproduction: http://rightsstatements.org/vocab/InC/1.0/
Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.