FK506 antagonizes apoptosis and c-jun protein expression in neuronal cultures.
FK506 is an immunosuppressive drug that binds to FK506 binding protein (FKBPs), a subgroup of cytosolic proteins called immunophillins. Previous works have revealed that FK506 protects neural cells from ischemia or excitotoxicity. Here we report that FK506 (10(-6) M) and not cyclosporine A (10(-6) M) blocks neuronal apoptosis induced by serum deprivation in rat neuronal cultures. In addition the immunohistochemical staining of C-jun protein in deprived cultures is markedly attenuated by FK506. The proportion of C-jun-positive neurons in control cultures, in serum-deprived cultures (48 h) and in serum-deprived cultures exposed to FK506 (10(-6) M) were 12.5%, 56.5% and 16.5%, respectively. The down-regulation of C-jun could play a major role in the anti-apoptotic action of FK506 in stressed neuronal cultures.
Unit of Neurobiology and Cellular Pathology, CRNS 6101, Laboratory of Histology and Cell Biology, Faculty of Medicine, Limoges, France.
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C
Yardin
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F
Terro
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M
Lesort
F
F
Esclaire
J
J
Hugon
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free; D016572:Cyclosporine / Q000494:pharmacology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology*
D016895:Culture Media, Serum-Free; D007166:Immunosuppressive Agents; D016755:Proto-Oncogene Proteins c-jun; D016572:Cyclosporine; D016559:Tacrolimus