Enhanced neurogenesis from neural progenitor cells with G1/S-phase cell cycle arrest is mediated by transforming growth factor beta1
| Autor: | Tae-Sun Kim, Tadashi Masuda, Hitoo Nishino, Fujiya Furuyama, Yoshiaki Isobe, Cha-Gyun Jung, Hideki Hida, Sachiyo Misumi, Susumu Urakawa |
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| Rok vydání: | 2008 |
| Předmět: |
Neurite
Dopamine Siderophores Deferoxamine S Phase Transforming Growth Factor beta1 Aphidicolin Cyclin-dependent kinase Pregnancy Tubulin Neurosphere Phosphoprotein Phosphatases Animals Smad3 Protein Progenitor cell Enzyme Inhibitors Rats Wistar Neurons biology General Neuroscience Stem Cells Neurogenesis G1 Phase Cell Differentiation Cyclin-Dependent Kinase 5 Cell cycle Neural stem cell Cell biology Rats biology.protein Female Neuroscience Receptors Transforming Growth Factor beta Cyclin-Dependent Kinase Inhibitor p27 Transforming growth factor Signal Transduction |
| Zdroj: | The European journal of neuroscience. 28(6) |
| ISSN: | 1460-9568 |
| Popis: | We have previously demonstrated that a G1/S-phase cell cycle blocker, deferoxamine (DFO), increased the number of new neurons from rat neurosphere cultures, which correlated with prolonged expression of cyclin-dependent kinase (cdk) inhibitor p27(kip1) [H. J. Kim et al. (2006)Brain Research, 1092, 1-15]. The present study focuses on neuronal differentiation mechanisms following treatment of neural stem/progenitor cells (NPCs) with a G1/S-phase cell cycle blocker. The addition of DFO (0.5 mm) or aphidicolin (Aph) (1.5 microm) to neurospheres for 8 h, followed by 3 days of differentiation, resulted in an increased number of neurons and neurite outgrowth. DFO induced enhanced expression of transforming growth factor (TGF)-beta1 and cdk5 at 24 h after differentiation, whereas Aph only increased TGF-beta1 expression. DFO-induced neurogenesis and neurite outgrowth were attenuated by administration of a cdk5 inhibitor, roscovitine, suggesting that the neurogenic mechanisms differ between DFO and Aph. TGF-beta1 (10 ng/mL) did not increase neurite outgrowth but rather the number of beta-tubulin III-positive cells, which was accompanied by enhanced p27(kip1) mRNA expression. In addition, TGF-beta receptor type II expression was observed in nestin-positive NPCs. Results indicated that DFO-induced TGF-beta1 signaling activated smad3 translocation from the cytoplasm to the nucleus. In contrast, TGF-beta1 signaling inhibition, via a TGF-beta receptor type I inhibitor (SB-505124), resulted in decreased DFO-induced neurogenesis, in conjunction with decreased p27(kip1) protein expression and smad3 translocation to the nucleus. These results suggest that cell cycle arrest during G1/S-phase induces TGF-beta1 expression. This, in turn, prompts enhanced neuronal differentiation via smad3 translocation to the nucleus and subsequent p27(kip1) activation in NPCs. |
| Databáze: | OpenAIRE |
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