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Differential regulation of glial cell line–derived neurotrophic factor (GDNF) expression in human neuroblastoma and glioblastoma cell lines
Author(s) -
Verity A.N.,
Wyatt T.L.,
Lee W.,
Hajos B.,
Baecker P.A.,
Eglen R.M.,
Johnson R.M.
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990115)55:2<187::aid-jnr6>3.0.co;2-t
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , cell culture , biology , microbiology and biotechnology , chemistry , endocrinology , medicine , biochemistry , receptor , genetics
Human SK‐N‐AS neuroblastoma and U‐87MG glioblastoma cell lines were found to secrete relatively high levels of glial cell line–derived neurotrophic factor (GDNF). In response to growth factors, cytokines, and pharmacophores, the two cell lines differentially regulated GDNF release. A 24‐hr exposure to tumor necrosis factor‐α (TNFα; 10 ng/ml) or interleukin‐1β (IL‐1β; 10 ng/ml) induced GDNF release in U‐87MG cells, but repressed GDNF release from SK‐N‐AS cells. Fibroblast growth factors (FGF)‐1, ‐2, and ‐9 (50 ng/ml), the prostaglandins PGA 2 , PGE 2 , and PGI 2 (10 μM), phorbol 12,13‐didecanoate (PDD; 10 nM), okadaic acid (10 nM), dexamethasone (1 μM), and vitamin D 3 (1 μm) also differentially effected GDNF release from U‐87MG and SK‐N‐AS cells. A result shared by both cell lines, was a two‐ to threefold increase in GDNF release by db‐cAMP (1 mM), or forskolin (10 μM). In general, analysis of steady‐state GDNF mRNA levels correlated with changes in extracellular GDNF levels in U‐87MG cells but remained static in SK‐N‐AS cells. The data suggest that human GDNF synthesis/release can be regulated by numerous facto, signaling through multiple and diverse secondary messenger systems. Furthermore, we provide evidence of differential regulation of human GDNF synthesis/release in cells of glial (U‐87MG) and neuronal (SK‐N‐AS) origin. J. Neurosci. Res. 55:187–197, 1999. © 1999 Wiley‐Liss, Inc.