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  • Title: Tyrosine kinase inhibitors and cycloheximide inhibit Li+ protection of cerebellar granule neurons switched to non-depolarizing medium.
    Author: Grignon S, Levy N, Couraud F, Bruguerolle B.
    Journal: Eur J Pharmacol; 1996 Nov 07; 315(1):111-4. PubMed ID: 8960871.
    Abstract:
    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.
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