Calcium ionophores can induce either apoptosis or necrosis in cultured cortical neurons

B. J. Gwag, L. M T Canzoniero, S. L. Sensi, J. A. Demaro, J. Y. Koh, M. P. Goldberg, M. Jacquin, D. W. Choi

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Cultured cortical neurons exposed for 24 h to low concentrations of the Ca2+ ionophores, ionomycin (250 nM) or A-23187 (100 nM), underwent apoptosis, accompanied by early degeneration of neurites, cell body shrinkage, chromatin condensation and internucleosomal DNA fragmentation. This death could be blocked by protein synthesis inhibitors, as well as by the growth factors brain-derived neurotrophic factor or insulin-like growth factor I. If the ionomycin concentration was increased to 1-3 μM, then neurons underwent necrosis, accompanied by early cell body swelling without DNA laddering, or sensitivity to cycloheximide or growth factors. Calcium imaging with Fura-2 suggested a possible basis for the differential effects of low and high concentrations of ionomycin. At low concentrations, ionomycin induced greater increases in intracellular Ca2+ concentration in neurites than in neuronal cell bodies, whereas at high concentrations, ionomycin produced large increases in intracellular Ca2+ concentration in both neurites and cell bodies. We hypothesize that the ability of low concentrations of Ca2+ ionophores to raise intracellular Ca2+ concentration preferentially in neurites caused early neurite degeneration, leading to loss of growth factor availability to the cell body and consequent apoptosis, whereas high concentrations of ionophores produced global cellular Ca2+ overload and consequent necrosis.

Original languageEnglish (US)
Pages (from-to)1339-1348
Number of pages10
JournalNeuroscience
Volume90
Issue number4
DOIs
StatePublished - Jun 1999

Fingerprint

Ionomycin
Calcium Ionophores
Neurites
Necrosis
Apoptosis
Ionophores
Neurons
Intercellular Signaling Peptides and Proteins
Protein Synthesis Inhibitors
Fura-2
Brain-Derived Neurotrophic Factor
Calcimycin
DNA Fragmentation
Cycloheximide
Insulin-Like Growth Factor I
Chromatin
Cell Body
Calcium
DNA

Keywords

  • Apoptosis
  • BDNF
  • Calcium ionophore
  • Cortical neurons
  • IGF-I
  • Necrosis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gwag, B. J., Canzoniero, L. M. T., Sensi, S. L., Demaro, J. A., Koh, J. Y., Goldberg, M. P., ... Choi, D. W. (1999). Calcium ionophores can induce either apoptosis or necrosis in cultured cortical neurons. Neuroscience, 90(4), 1339-1348. https://doi.org/10.1016/S0306-4522(98)00508-9

Calcium ionophores can induce either apoptosis or necrosis in cultured cortical neurons. / Gwag, B. J.; Canzoniero, L. M T; Sensi, S. L.; Demaro, J. A.; Koh, J. Y.; Goldberg, M. P.; Jacquin, M.; Choi, D. W.

In: Neuroscience, Vol. 90, No. 4, 06.1999, p. 1339-1348.

Research output: Contribution to journalArticle

Gwag, BJ, Canzoniero, LMT, Sensi, SL, Demaro, JA, Koh, JY, Goldberg, MP, Jacquin, M & Choi, DW 1999, 'Calcium ionophores can induce either apoptosis or necrosis in cultured cortical neurons', Neuroscience, vol. 90, no. 4, pp. 1339-1348. https://doi.org/10.1016/S0306-4522(98)00508-9
Gwag, B. J. ; Canzoniero, L. M T ; Sensi, S. L. ; Demaro, J. A. ; Koh, J. Y. ; Goldberg, M. P. ; Jacquin, M. ; Choi, D. W. / Calcium ionophores can induce either apoptosis or necrosis in cultured cortical neurons. In: Neuroscience. 1999 ; Vol. 90, No. 4. pp. 1339-1348.
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