Activation of G proteins bidirectionally affects apoptosis of cultured cerebellar granule neurons.
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.
Yan
G M
GM
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, USA.
Lin
S Z
SZ
Irwin
R P
RP
Paul
S M
SM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D003470:Culture Media; D019204:GTP-Binding Proteins / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010455:Peptides; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
D003470:Culture Media; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; C037500:mastoparan; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011188:Potassium