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| 題名: | Activation of NMDA Receptor Partly Involved in β-bungarotoxin-induced Neurotoxicity in Cultured Primary Neurons |
| 作者: | Tseng, Wen-Pei;Shoei-Yn Lin-Shiau |
| 貢獻者: | 運動健康所 |
| 關鍵詞: | β-Bungarotoxin;Neurotoxicity;NMDA receptor binding;Oxidative stress;Caspase activity |
| 日期: | 2003-03
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| 上傳時間: | 2014-01-15T04:02:39Z
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| 出版者: | Elsevier B.V. |
| 摘要: | In this study, we demonstrated that a snake presynaptic toxin, beta-bungarotoxin (beta-BuTX), was capable of binding to NMDA receptors of the cultured primary neurons (cerebellar granule neurons, CGNs). We labeled beta-BuTX with fluorescent FITC (FITC-beta-BuTX) and showed that the binding of FITC-beta-BuTX was inhibited by unlabeled beta-BuTX and MK801 (an NMDA receptor antagonist). Meanwhile, the binding of [3H]-MK801 was also reduced by unlabeled MK801 and beta-BuTX. In addition, beta-BuTX produced a very potent neurotoxic effect on mature CGNs with the EC(50) of 3ng/ml (equivalent to 144pM), but was less effective in immature CGNs. We explored the signaling pathway of neuronal death and found that it was apparently due to the excessive production of reactive oxygen species (ROS) induced by beta-BuTX. MK801 and antioxidants (Vitamin C, N-acetylcysteine (NAC), melatonin, epigallocatechin gallate (EGCG), superoxide dismutase (SOD) and catalase) attenuated not only ROS production but also beta-BuTX-neurotoxicity. The downstream signaling of ROS was identified as the activation of caspase-3. Caspase inhibitor (z-DEVD-fmk) and antioxidants depressed both caspase-3 activation and neurotoxicity. Based on these findings and our previous reports, we conclude that the binding and activation of NMDA receptors by beta-BuTX was crucial step to produce the potent neurotoxic effect. The binding of NMDA receptors resulted in excessive Ca(2+) influx, followed by ROS production and activation of caspase-3. This snake toxin is considered not only to be a useful tool for exploring the death-signaling pathway of neurotoxicity, but also provides a model for searching neuroprotective agents. |
| 關聯: | Neurochemistry International, 42(4): 333-344 |
| 顯示於類別: | [運動健康研究所] 期刊論文
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