Activation of NMDA receptor partly involved in β-bungarotoxin-induced neurotoxicity in cultured primary neurons

Wen-Pei Tseng, Shoei Yn Lin-Shiau

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21 Citations (Scopus)


In this study, we demonstrated that a snake presynaptic toxin, β-bungarotoxin (β-BuTX), was capable of binding to NMDA receptors of the cultured primary neurons (cerebellar granule neurons, CGNs). We labeled β-BuTX with fluorescent FITC (FITC-β-BuTX) and showed that the binding of FITC-β-BuTX was inhibited by unlabeled β-BuTX and MK801 (an NMDA receptor antagonist). Meanwhile, the binding of [3H]-MK801 was also reduced by unlabeled MK801 and β-BuTX. In addition, β-BuTX produced a very potent neurotoxic effect on mature CGNs with the EC50 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 β-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 β-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 β-BuTX was crucial step to produce the potent neurotoxic effect. The binding of NMDA receptors resulted in excessive Ca2+ 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.

Original languageEnglish
Pages (from-to)333-344
Number of pages12
JournalNeurochemistry International
Issue number4
Publication statusPublished - 2003 Mar 1

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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