Molecular mechanisms of enhanced susceptibility to apoptosis in differentiating oligodendrocytes

Several studies have shown that the progression of oligodendrocyte progenitors along the lineage correlates with increased susceptibility to death stimuli. The molecular basis of this phenomenon remains unclear. This study demonstrates that the protein levels of several proapoptotic molecules, including Bax, Bad (nonphosphorylated form), and certain caspase proforms, increase during oligodendrocyte development. In contrast, the steady-state levels of antiapoptotic molecules, such as Bcl2 and Bcl(XL), remain constant. This altered equilibrium between proapoptotic and antiapoptotic molecules correlates with increased cytochrome C in the cytosol. We conclude that, as oligodendrocytes mature, their susceptibility to apoptosis increases because of a change in the balance between protective mechanisms and proapoptotic pathways. This suggests the possible existence of a death susceptibility program, which is intrinsic to differentiating oligodendrocyte progenitors. (C) 2002 Wiley-Liss, Inc.