Activation of PKC isoforms by ATP/UTP and PMA in murine astrocytes |
| |
Authors: | G Y Sun J Xu Z Liao S-C Lo G A Weisman |
| |
Institution: | Thomas Jefferson University, Philadelphia, PA, USA |
| |
Abstract: | Abnormal myelin formation appears to be one defect contributing to the neuropathology associated with the fetal alcohol syndrome, the major cause of noncongenital mental retardation. Using the CG-4 cell line we previously showed that 25–75 m m ethanol (EtOH) down-regulates myelin basic protein (MBP) expression in differentiating oligodendrocytes (OLGs) without affecting the 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) expression or morphological development (Bichenkov and Ellingson 2001). Here we observed that a relatively low concentration of 12-phorbol-13-myristate acetate (PMA) mimicked the EtOH-caused inhibition of MBP expression without affecting CNP expression or morphology. The inhibition of MBP expression by 100 m m EtOH or 1 n m PMA was completely counteracted by three inhibitors of protein kinase C (PKC); bisinodoylmaleimide I, chelerythrine chloride, and calphostin C, indicating that EtOH down-regulated MBP expression by activating PKC. We investigated whether the EtOH-caused activation resulted in part from up-regulation of the expression of PKC isozymes. Of 11 PKC isozymes examined, CG-4 OLGs expressed nine; PKC α, β1, β2, δ, ε, λ, μ, nu and zeta; while PKC isozymes γ and theta were not detected. Only five PKC isozymes, α, β1, β2, μ, and nu, displayed developmental changes in expression. However, EtOH did not up-regulate the early expression of any PKC isozyme during the first two days of differentiation, the developmental stage when it down-regulates the MBP expression in CG-4 cells. The results indicate that EtOH delays MBP expression by activating at least one phorbol ester-sensitive PKC isozyme in differentiating oligodendrocytes without up-regulating its expression. Acknowledgements: Support: NIAAA Grant AA072185. |
| |
Keywords: | |
|
|