Regulation of the rat oligodendroglia cell line OLN-93 by antisense transfection of butyrylcholinesterase

Butyrylcholinesterase (BChE) is a glial cell marker with unknown function. For neuroepithelial cells,:BChE has been shown to regulate cell division an d expression of the postmitotic marker acetylcholinesterase (AChE), while s imilar studies are lacking for glial cells. By transducing an antisense-5'B ChE cDNA expression vector via calcium phosphate precipitation, we have ana lyzed the effect of BChE inhibition on proliferation and differentiation of rat oligodendroglia-derived OLN-93 cells. OLN-93 cells were chosen because they are highly proliferative, while expressing markers of differentiated oligodendrocytes (Richter-Landsberg and Heinrich, 1996). First, we establis hed that OLN-93 cells do express BChE protein, albeit chiefly in an inactiv e state, and that BChE was decreased by antisense-5'BChE transfection. Cell proliferation was also strongly diminished, protein kinase C (PKC alpha) w as upregulated, and expression of cytoskeletal and cell surface proteins wa s altered. In particular, immunoreactivities of the intermediate filament p roteins vimentin and the cell adhesion protein F11 were detected, indicatin g that BChE-inhibited OLN-93 cells have shifted toward an astrocytic phenot ype. These data support a role of the glia marker BChE in CNS glial cell pr oliferation and differentiation, achieved via a nonenzymatic mechanism. The possible biomedical impact of BChE protein, e.g., on CNS nerve regeneratio n, is briefly discussed. (C) 2000 Wiley-Liss, Inc.