Calcium-activated NO production plays a role in neuronal death induced by β-bungarotoxin in primary cultures of cerebellar granular neurons

Wen Pei Tseng, Shoei Yn Lin-Shiau

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

The aim of this study was to elucidate the mechanism underlying the neurotoxic effect of β-bungarotoxin (β-BuTX) on cultured cerebellar granular neurons (CGN). β-BuTX had a potent time- and concentration-dependent neurotoxic effect on mature CGN. β-BuTX appeared to destroy initially the neurites and then caused neuronal death by both apoptotic and necrotic processes. Inspection using Nomarski optics showed that these neurons displayed morphological features of necrotic cells, including cell swelling, loss of membrane integrity and eventual dissolution of the cell. Staining with the fluorescent dye Hoechst 33258 showed that β-BuTX-treated neuron bodies stained more densely with smaller apoptotic bodies. Using microspectrofluorimetry and fura-2 to measure cytosolic [Ca2+] ([Ca2+]i), β-BuTX markedly increased [Ca2+]i. BAPTA-AM, EGTA, MK 801 and diltiazem not only attenuated the β-BuTX-mediated rise in [Ca2+]i but also attenuated β-BuTX-mediated neurotoxicity. In addition, these Ca2+ inhibitors prevented the β-BuTX-induced generation of reactive nitrogen species. The NO synthase inhibitor NG-methyl-L-arginine) also exhibited neuroprotection. This is the first report showing that β-BuTX-induced CGN death is mediated, at least in part, by excessive generation of NO triggered by [Ca2+]i overloading. Activation of NMDA receptors and L-type calcium channels is apparently involved in the increase in [Ca2+]i induced by this neurotoxin. This potent neurotoxin will be a useful tool for studying neurotoxic processes and using this model system will allow us to find neuroprotective agents.

原文English
頁(從 - 到)451-461
頁數11
期刊Naunyn-Schmiedeberg's Archives of Pharmacology
367
發行號5
DOIs
出版狀態Published - 2003 五月 1

All Science Journal Classification (ASJC) codes

  • Pharmacology

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