Glucocorticoid inhibits growth factor-induced differentiation of hippocampal progenitor HiB5 cells
- Authors
- Son G.H.; Geum D.; Jung H.; Kim K.
- Issue Date
- 2001
- Keywords
- Differentiation; Extracellular signal-regulated kinases1/2; Glucocorticoid; Hippocampal progenitor; Protein tyrosine phosphatase
- Citation
- Journal of Neurochemistry, v.79, no.5, pp 1013 - 1021
- Pages
- 9
- Indexed
- SCOPUS
- Journal Title
- Journal of Neurochemistry
- Volume
- 79
- Number
- 5
- Start Page
- 1013
- End Page
- 1021
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/22847
- DOI
- 10.1046/j.1471-4159.2001.00634.x
- ISSN
- 0022-3042
1471-4159
- Abstract
- In the present study, we investigated the effect of glucocorticoid on neuronal differentiation of hippocampal progenitor HiB5 cells. Dexamethasone (DEX), a synthetic glucocorticoid, inhibited platelet-derived growth factor (PDGF)-induced differentiation of HiB5 cells. The inhibitory effect of DEX was antagonized by RU486, a glucocorticoid receptor (GR) antagonist, indicating the GR-mediated processes. Nestin mRNA level was decreased and midsize neurofilament (NF-M) mRNA level was increased as a function of neuronal differentiation. DEX significantly blocked PDGF-induced down-regulation of nestin mRNA level, and up-regulation of NF-M mRNA level, which were similar to those of undifferentiated cells. DEX inhibited PDGF-induced activation of cyclic AMP-responsive element binding protein (CREB) and AP-1, suggesting that glucocorticoid interfered with signal transduction cascades linking the PDGF receptor and downstream transcription factors. Indeed, DEX reduced PDGF-induced phosphorylation of extracellular signal-regulated kinases1/2 (ERK1/2). Tyrosine phosphatase inhibitor reversed the effect of DEX on ERK1/2. In accordance with this finding, blockage of ERK1/2 signaling pathway with PD098059, a potent inhibitor for Ras/ERK pathway, mimicked the inhibitory effect of DEX on differentiation processes. Taken together, these results indicate that glucocorticoid inhibits PDGF-induced differentiation of hippocampal progenitor HiB5 cells by inhibiting the ERK1/2 signaling cascade via a tyrosine phosphatase-dependent mechanism.
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Collections - 3. Graduate School > Biomedical Research Center > 1. Journal Articles
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