Mitogenic and differetiative effects of iron on schwann cells

Abstract

Recent studies indicate that iron and transferrin (Tf) play significant roles in growth and differentiation of oligodendrocytes, the myelin-forming cells of the CNS. On the other hand, the relationship of iron to Schwann cells and PNS myelination has not yet been elucidated. In this study, we hypothesize that activation of Schwann cell iron metabolism could recapitulate the relationship of iron to oligodendrocytes and myelination and could be essential for the process of nerve regeneration. Therefore, the effect of iron on Schwann cell line D6P2T was examined with regard to its proliferation and differentiation. It was found that D6P2T cells expressed the receptors for Tf similar to Schwann sell in vivo. We then investigated the effect of iron citrate at various concentrations (50-100ug/ml) on Schwann cell proliferation using MTT assay, which was confirmed by trypan blue dye exclusion method. The results demonstrated that Schwann cell exposed to 50 ug/ml iron for 24 h increased cell proliferation by 20%, when compared to untreated Schwann cells. Percent proliferation of Schwann cell was diminished with increasing concentration of iron, but still higher than that of the untreated cells. Exposure to iron also reduced the expression of Tf receptors on Schwann cell surface and increased the expression of iron storage protein ferritin as determined by flow cytometry and immunoblot, respectively, suggesting that iron treatment elevated intracellular iron levels. However, it appeared that exposure of Schwann cells with increasing concentration of iron significantly decreased ferritin levels without showing a dose-dependent cytotoxicity of iron. We then examined the effect of iron on the expression of myelin gene associated with schwann cell differentiation. RT-PCR results showed that exposure of Schwann cells to iron induced mRNA expression of myelin protein zero (P0) and myelin basic protein (MBP) in a dose-dependent manner. Thus, these findings suggest that iron may be an indispensable factor for Schwann cell proliferation and differentiation.