Neuronal survival activity of s100betabeta is enhanced by calcineurin inhibitors and requires activation of NF-kappaB. FASEB J 1999 Sep;13(12):1611-20
Date
08/27/1999Pubmed ID
10463953DOI
10.1096/fasebj.13.12.1611Scopus ID
2-s2.0-0032851616 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
S100betabeta is a calcium binding, neurotrophic protein produced by nonneuronal cells in the nervous system. The pathway by which it enhances neuronal survival is unknown. Here we show that S100betabeta enhances survival of embryonic chick forebrain neurons in a dose-dependent manner. In the presence of suboptimal amounts of S100betabeta, neuronal survival is enhanced by the immunosuppressants FK506 and cyclosporin A at concentrations that inhibit calcineurin, which is present in these cells. Rapamycin, an immunosuppressant that does not inhibit calcineurin, did not enhance cell survival. Cypermethrin, a direct and highly specific calcineurin inhibitor, mimicked the immunophilin ligands in its neurotrophic effect. None of the drugs stimulated neuronal survival in the absence of S100betabeta. In the presence of suboptimal amounts of S100betabeta, FK506, cyclosporin A, and cypermethrin (but not rapamycin) also increased NF-kappaB activity, as measured by immunofluorescence of cells stained with antibody to the active subunit (p65) and by immunoblotting of nuclear extracts. Antioxidant and glucocorticoid inhibitors of NF-kappaB decreased both the amount of active NF-kappaB and the survival of neurons caused by S100betabeta alone or in the presence of augmenting drugs. We conclude that S100betabeta enhances the survival of chick embryo forebrain neurons through the activation of NF-kappaB.
Author List
Alexanian AR, Bamburg JRAuthor
Arshak R. Alexanian VMD, PhD Adjunct Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntioxidants
Brain Chemistry
Calcineurin Inhibitors
Calcium-Binding Proteins
Cattle
Cell Nucleus
Cell Survival
Cells, Cultured
Chick Embryo
Coumarins
Cyclosporine
Dexamethasone
Dimerization
Immunophilins
Immunosuppressive Agents
Isocoumarins
Macromolecular Substances
NF-kappa B
Nerve Growth Factors
Neurons
Prosencephalon
Pyrethrins
Pyrrolidines
S100 Calcium Binding Protein beta Subunit
S100 Proteins
Serine Proteinase Inhibitors
Sirolimus
Tacrolimus
Thiocarbamates
