AP-1 Activity during the Growth, Differentiation, and Death of O-2A Lineage Cells

Abstract

Oligodendrocyte differentiation has been correlated with AP-1 activity, being low in progenitors and high in differentiated cells. In this study we have carried out a detailed temporal analysis of AP-1 activity in oligodendrocyte-type-2 astrocyte (O-2A) lineage cells. We show that low AP-1 activity in progenitor cells depended on the application of growth factors. Treatment of cells with B104-conditioned medium induced high AP-1 activity, increased process length, and improved growth. The role of AP-1 in proliferation and process extension was emphasized when progenitor cells overexpressing a c-Jun dominant-negative mutant had impaired growth and shortened processes. AP-1 DNA-binding activity during O-2A differentiation in vitro showed an initial down-regulation followed by up-regulation after 2 days. Increased AP-1 levels in oligodendrocytes were inhibited by overexpression of bcl-2, indicating that AP-1 in mature oligodendrocytes is involved in the regulation of apoptosis. Prevention of cell death by bcl-2 in oligodendrocytes was accompanied by progressive differentiation and expression of MOG and PLP.