Effects of Altered Cyclophilin A Expression on Growth and Differentiation of Human and Mouse Neuronal Cells

Publisher Website
Google Scholar
Abstract
1. Cyclophilin A (CyP-A), a soluble cytoplasmic immunophilin, is known for its involvement in T cell differentiation and proliferation. Although CyP-A has a pivotal role in the immune response, it is most highly concentratedin brain, where its functions are largely unknown. 2. We reported previously that a murine neuroblastoma (NB-P2) cellline can partially differentiate into neurons when treated with cyclosporin A (CyS-A), implicating a role for CyP-A in neuronal differentiation (Hovland et al. [1999]. Neurochem. Int. 3:229–235). 3. The role of CyP-A in regulating neuronal growth and differentiation is not well defined. To investigate this, we first tested the utility of retroviral-mediated gene transfer and expression in human embryonic brain (HEB) and NB-P2 cells. Second, we examined the effects of retroviral-mediated overexpression or antisense-mediated reduction of CyP-A in HEB and NB-P2 cells. 4. Our data show that retroviral vectors are efficient for stable gene transfer and expression in both cell lines. Moreover, neither overexpression nor reduction of CyP-A expression in NB-P2 cells altered the growth rate or induced differentiation. More importantly, the up- or down-regulation of CyP-A expressiondid not affect the magnitude of cAMP-induced NB-P2 differentiation. However, overexpression of CyP-A increased the growth rate of HEB cells. 5. In summary, the utility of retroviral vectors for stable gene expression in human embryonic brain and murine neuroblastoma cells was shown. Furthermore,a novel role for CyP-A in augmenting the proliferation of human embryonic braincells was demonstrated in vitro.