Protection of neuro‐2a cells against calcium ionophore cytotoxicity by gangliosides

K. Nakamura, G. Wu, R. W. Ledeen

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Gangliosides are known to assert both neuritogenic and neuroprotective effects when applied to a variety of neuroblastoma and primary neuronal cultures. We have developed a model employing Neuro‐2a Neuroblastoma cells with Ca2+ ionophore A23187 as neurotoxic agent causing neurite retraction and eventual cell death. Gangliosides attenuated the toxicity of this substance, increasing both cell survival and neurite stability. In one series of experiments, cells were exposed to A23187 for 24 hr and then incubated in fresh medium (washout) for 18 hr; gangliosides were present at varying times. The paradigm in which cells were only preincubated (2 hr) with ganglioside provided no benefit, nor did incubation of the cells in both ionophore and ganglioside during the 24‐hr exposure period. Significant protection was achieved by exposing the cells to ganglioside after washout of A23187, or continuously throughout the whole period. Bovine brain ganglioside mixture and the four major components (GM1, GDla, GDlb, GTlb) applied individually were all effective. By contrast, GM3 and GMl‐alcohol, a neutral derivative of GM1, provided little or no protection. Dichlorobenzamil an inhibitor of the Na+ −Ca2+ exchanger, tended to block the neurite stabilizing effect of gangliosides, suggesting that the mechanism might involve potentiation of this antiporter.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalJournal of Neuroscience Research
Volume31
Issue number2
DOIs
StatePublished - Feb 1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Keywords

  • Na−Caexchanger
  • Neuro‐2a cells
  • calcium
  • calcium ionophore
  • cytotoxicity
  • dichlorobenzamil
  • gangliosides

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