Abstract
We have shown that pre-treatment with deferoxamine (DFO: cell cycle blocker in G1/S phase) increase the number of neurons from neural stem/progenitor cells (NPCs) with relation to prolonged enhancement of p27kip1 mRNA expression, and transfection of p27kip1 induced neuroD promoter activation and increase of the number of β-tubulin III-positive cells. To investigate the molecular mechanism of neuronal differentiation by cell cycle blocker in detail, we focused on the relation between p27kip1 and cyclin-dependent kinase 5 (cdk5). As cdk5 is known to bind with p27kip1 and an cdk5 activator p35, the expression of cdk5 or p35 was investigated at the end point of DFO treatment for 8 hours and at 24 hours after differentiation to neurons. Expression of cdk5 mRNA was significantly elevated after the differentiation, although it was decreased during DFO treatment. On the other hand, expression of p35 mRNA was reduced during DFO treatment, but did not alter after differentiation. Data suggest that enhancement of cdk5 expression following to transient decrease during treatment would be included in the mechanism of neuronal differentiation followed by cell cycle arrest. [J Physiol Sci. 2007;57 Suppl:S132]
