Activation of G proteins bidirectionally affects apoptosis of cultured cerebellar granule neurons

J Neurochem. 1995 Dec;65(6):2425-31. doi: 10.1046/j.1471-4159.1995.65062425.x.

Abstract

Cultured cerebellar granule neurons maintained in depolarizing concentrations of K+ (25 mM) and then switched to physiological concentrations of K+ (5 mM) undergo apoptosis. We now report that activation of specific G proteins robustly and bidirectionally affects apotosis of cultured rat cerebellar granule neurons. Stimulation of Gs with cholera toxin completely blocks apoptosis induced by nondepolarizing concentrations of K+, whereas stimulation of Go/Gi with the wasp venom peptide mastoparan induces apoptosis of cerebellar granule neurons even in high (depolarizing) concentrations of K+. Moreover, pretreatment of cerebellar granule neurons with cholera toxin attenuates neuronal death induced by mastoparan. By contrast, pertussis toxin, cell-permeable analogues of cyclic AMP, and activators of protein kinase A do not affect apoptosis of cultured cerebellar granule neurons. These data suggest that G proteins may function as key switches for controlling the programmed death of mammalian neurons, especially in the developing CNS.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cells, Cultured
  • Cerebellum / cytology*
  • Cerebellum / drug effects
  • Cholera Toxin / pharmacology
  • Culture Media
  • GTP-Binding Proteins / physiology*
  • Intercellular Signaling Peptides and Proteins
  • Neurons / drug effects
  • Neurons / physiology*
  • Peptides
  • Pertussis Toxin
  • Potassium / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Virulence Factors, Bordetella / pharmacology
  • Wasp Venoms / pharmacology

Substances

  • Culture Media
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Virulence Factors, Bordetella
  • Wasp Venoms
  • mastoparan
  • Cholera Toxin
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Potassium