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December 1, 1993Proceedings of the National Academy of SciencesOpen Access

Induction of apoptosis in cerebellar granule neurons by low potassium: inhibition of death by insulin-like growth factor I and cAMP.

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Authors

SDSantosh R. D’MelloItron (United States)CGCinzia GalliInstitute of Neurobiology and Molecular MedicineTCTeresa CiottiInstitute of Cell Biology and Neurobiology

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Overview

In vitro study reveals that low potassium induces transcription-dependent apoptosis in cerebellar granule neurons, indicating that IGF-I and cAMP promote neuronal survival.

Key Points

  • To determine the mechanism of cell death triggered by lowering extracellular potassium in cultured cerebellar granule neurons and to evaluate factors that prevent this degeneration.
  • Switched differentiated cerebellar granule neuron cultures from high potassium (25 mM) medium to physiological low potassium (5 mM) medium.
  • Assessed neuronal viability, DNA fragmentation, and the protective effects of transcription and translation inhibitors.
  • Screened neurotrophic factors and intracellular messengers, including insulin-like growth factor I (IGF-I), cAMP, and phorbol 12-myristate 13-acetate (PMA), for survival-promoting activity.
  • Shifting to 5 mM potassium triggered apoptotic death characterized by internucleosomal genomic DNA cleavage.
  • Transcription and translation inhibitors suppressed low-potassium-induced apoptosis, indicating a requirement for newly synthesized gene products.
  • Insulin-like growth factor I and cAMP prevented apoptosis in low potassium, whereas other growth factors and the protein kinase C activator PMA did not support survival.

Cite This Study

D’Mello et al. (1993) studied this question.

synapsesocial.com/papers/6a6f8e076c240de38cdb83cahttps://doi.org/10.1073/pnas.90.23.10989
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