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Regulation of Glial Cell Line‐Derived Neurotrophic Factor Release from Rat C6 Glioblastoma Cells
Author(s) -
Verity A. Neil,
Wyatt T. L.,
Hajos B.,
Eglen R. M.,
Baecker P. A.,
Johnson R. M.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020531.x
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , gdnf family of ligands , endocrinology , biology , medicine , signal transduction , microbiology and biotechnology , forskolin , neuroglia , proinflammatory cytokine , chemistry , biochemistry , receptor , immunology , inflammation , central nervous system , stimulation
We have monitored glial cell line‐derived neurotrophic factor (GDNF) secretion from rat C6 glioblastoma cells by ELISA. Representative cytokines, neurotrophins, growth factors, neuropeptides, and pharmacological agents were tested for their ability to modulate GDNF release. Whereas most factors tested had minimal effect, a 24‐h treatment with fibroblast growth factor‐1, −2, or −9 elevated secreted GDNF protein levels five‐ to 10‐fold. The proinflammatory cytokines interleukin‐1β, interleukin‐6, tumor necrosis factor‐α, and lipopolysaccharide elevated GDNF release 1.5‐ to twofold. Parallel studies aimed at elucidating intracellular events that may regulate GDNF synthesis/release demonstrated the involvement of multiple signaling pathways. GDNF levels were increased by phorbol 12,13‐didecanoate (10 n M ) activation of protein kinase C, the Ca 2+ ionophore A23187 (1 µ M ), okadaic acid (10 n M ) inhibition of type‐2A protein phosphatases, nitric oxide donors (1 m M ), and H 2 O 2 (1 m M )‐induced oxidative stress. Elevation of cyclic AMP levels by either forskolin (10 µ M ) or dibutyryl cyclic AMP (1 m M ) repressed GDNF secretion, as did treatment with the glucocorticoid dexamethasone (1 µ M ). Our results demonstrate that diverse biological factors are capable of modulating GDNF protein levels and that multiple signal transduction systems can regulate GDNF synthesis and/or release.