Suramin inhibits β-bungarotoxin-induced activation of N-methyl-D-aspartate receptors and cytotoxicity in primary neurons

Wen Pei Tseng, Shoei Yn Lin-Shiau

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We demonstrated that β-bungarotoxin (β-BuTX), a snake presynaptic neurotoxin, exhibited a potent cytotoxic effect on cultured cerebellar granule neurons. The mechanism of action of β-BuTX and the cytoprotective agents against β-BuTX were studied. The neuronal death of cerebellar granule neurons induced by β-BuTX was manifested with apoptosis and necrosis processes as revealed by neurite fragmentation, morphological alterations, and staining apoptotic bodies with the fluorescent dye Hoechst 33258. By means of microspectrofluorimetry and fura-2, we measured intracellular Ca2+ concentration, [Ca2+]i and found that [Ca2+]i was increased markedly prior to the morphological changes and cytotoxicity. The downstream pathway of the increased [Ca2+]i was investigated: there was increased production of free radicals, decreased mitochondrial membrane potential, and depleted cellular ATP content. MK801 and suramin effectively suppressed these detrimental effects of β-BuTX. Furthermore, the [3H]MK801 binding was reduced by unlabeled MK801, β-BuTX, and suramin. Thus, activation of N-methyl-D-aspartate (NMDA) receptors appeared to play a crucial role in the cytotoxic effects following βBuTX exposure. In conclusion, the novel finding of this study was that a polypeptide β-BuTX exerted a potent cytotoxic effect through sequential events, including activating NMDA receptors followed by increasing [Ca2+]i, ROS production, and impaired mitochondrial energy metabolism. Suramin, clinically used as a trypanocidal agent, was an effective antagonist against β-BuTX. Data suggest that suramin might have value to detect the possible pathway of certain neuropathological disorders.

Original languageEnglish
Pages (from-to)45-55
Number of pages11
JournalToxicology and Applied Pharmacology
Volume189
Issue number1
DOIs
Publication statusPublished - 2003 May 15

Fingerprint

Suramin
Bungarotoxins
Cytotoxicity
N-Methyl-D-Aspartate Receptors
Neurons
Chemical activation
Trypanocidal Agents
Bisbenzimidazole
Snakes
Fura-2
Mitochondrial Membrane Potential
Neurotoxins
Neurites
Fluorescent Dyes
Energy Metabolism
Free Radicals
Necrosis
Adenosine Triphosphate
Apoptosis
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

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title = "Suramin inhibits β-bungarotoxin-induced activation of N-methyl-D-aspartate receptors and cytotoxicity in primary neurons",
abstract = "We demonstrated that β-bungarotoxin (β-BuTX), a snake presynaptic neurotoxin, exhibited a potent cytotoxic effect on cultured cerebellar granule neurons. The mechanism of action of β-BuTX and the cytoprotective agents against β-BuTX were studied. The neuronal death of cerebellar granule neurons induced by β-BuTX was manifested with apoptosis and necrosis processes as revealed by neurite fragmentation, morphological alterations, and staining apoptotic bodies with the fluorescent dye Hoechst 33258. By means of microspectrofluorimetry and fura-2, we measured intracellular Ca2+ concentration, [Ca2+]i and found that [Ca2+]i was increased markedly prior to the morphological changes and cytotoxicity. The downstream pathway of the increased [Ca2+]i was investigated: there was increased production of free radicals, decreased mitochondrial membrane potential, and depleted cellular ATP content. MK801 and suramin effectively suppressed these detrimental effects of β-BuTX. Furthermore, the [3H]MK801 binding was reduced by unlabeled MK801, β-BuTX, and suramin. Thus, activation of N-methyl-D-aspartate (NMDA) receptors appeared to play a crucial role in the cytotoxic effects following βBuTX exposure. In conclusion, the novel finding of this study was that a polypeptide β-BuTX exerted a potent cytotoxic effect through sequential events, including activating NMDA receptors followed by increasing [Ca2+]i, ROS production, and impaired mitochondrial energy metabolism. Suramin, clinically used as a trypanocidal agent, was an effective antagonist against β-BuTX. Data suggest that suramin might have value to detect the possible pathway of certain neuropathological disorders.",
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Suramin inhibits β-bungarotoxin-induced activation of N-methyl-D-aspartate receptors and cytotoxicity in primary neurons. / Tseng, Wen Pei; Lin-Shiau, Shoei Yn.

In: Toxicology and Applied Pharmacology, Vol. 189, No. 1, 15.05.2003, p. 45-55.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Lin-Shiau, Shoei Yn

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