Acute course of deferoxamine promoted neuronal differentiation of neural progenitor cells through suppression of Wnt/beta-catenin pathway: A novel efficient protocol for neuronal differentiation

作者：Ziaei Amin; Ardakani Mohammad Reza Piri; Hashemi Motahare Sadat; Peymani Maryam; Ghaedi Kamran^*; Baharvand Hossein; Nasr Esfahani Mohammad Hossein

来源：Neuroscience Letters, 2015, 590: 138-144.

DOI：10.1016/j.neulet.2015.01.083

• beta-catenin
• Deferoxamine
• Iron
• Neuronal differentiation
• Neural progenitor cell

Neural progenitor cells (NPCs) are feasible therapeutically model cells in regenerative medicine. However, a number of obstacles oppose their applications including insufficiency in differentiation protocols. These complications should be overwhelmed to obtain a significant clinical application. Deferoxamine (DFO), as a small molecule with a clinically high-affinity to chelate intracellular Iron, has been granted orphan drug status for treatment of traumatic spinal cord injury, while its neuroprotective function is not well understood. The aim of the present study is evaluating whether DFO could modulate neuronal differentiation process of NPCs. A varies concentrations of DFO were used to promote neuronal differentiation of mouse and human NPCs with different serum condition as an extracellular source of Iron. Several neural markers were assessed by RT-qPCR and Western analysis. Meanwhile beta-catenin content was evaluated as key member of Wnt pathway. The maximal neuronal differentiation rate was observed when treating cells were treated with acute dosage of DFO (100 mu M) for 6 h in serum free condition. This treatment produced a significant increase in expression of neuronal markers and resulted in dramatically decrease in expression of glial markers. The protein content of beta-catenin was also decreased by this treatment. Despite of chronic concentration of DFO, which reduced the size of EBs apparently due to G1/S arrest of cell cycle as known features of DFO. Application of acute courses of DFO increased neuronal differentiation rate of NPCs in serum free conditions. We concluded that suppression of Wnt/beta-catenin pathway,was induced through chelating of intracellular Iron due to DFO treatment. These findings help to understand therapeutic benefit of DFO as a neuroprotective agent.

• 出版日期2015-3-17