Tyrosine kinase inhibitors and cycloheximide inhibit Li+ protection of cerebellar granule neurons switched to non-depolarizing medium.
Recently, it has been shown that Li+ robustly enhances the survival of cerebellar granule neurons acutely switched to non-depolarizing medium after maturing in vitro, a condition which elicits massive apoptotic death in this cell type. Tyrosine protein phosphorylation is known to underlie the activity of a number of trophic factors. This prompted us to investigate whether specific tyrosine kinase inhibitors could modulate the Li+ protection of cultured granule neurons switched to non-depolarizing medium. Genistein and herbimycin A dose dependently abolished the Li+ effect. Furthermore, this effect was substantially prevented by the translational inhibitor cycloheximide, suggesting that it requires de novo protein synthesis. Overall, these results suggest that Li+ protection of cerebellar granule neurons switched to non-depolarizing medium involves tyrosine kinases and transcriptional activation.
Grignon
S
S
Laboratoire de Pharmacologie Médicale, Faculté de Médecine-Timone, Marseille, France.
Levy
N
N
Couraud
F
F
Bruguerolle
B
B
D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008094:Lithium / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011500:Protein Synthesis Inhibitors; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D003513:Cycloheximide; D008094:Lithium; D019833:Genistein; D011505:Protein-Tyrosine Kinases