H2O2-induced apoptotic death in serum-deprived cultures of oligodendrogliaorigin is linked to cell differentiation

When deprived of serum, oligodendroglialike (OLN 93) cells grown on poly-l- lysine-coated culture dishes cease to proliferate after 3 days and morpholo gically extend many fibers resembling morphologically differentiated, immat ure oligodendrocytes, At this time no cell death is apparent unless serum d eprivation is extended for a period longer than 1 week. After 3 days in ser um-deprived medium, treatment of cells with 1 mM H2O2 for 30 min facilitate s apoptotic cell death, even when serum is added during the recovery period . Both serum-deprived, differentiated cells, and proliferating cells, respo nd to H2O2 by an initial growth arrest followed by growth resumption after 48 hr. However proliferating cells show resistance to the apoptotic effect of H2O2. This is correlated with growth arrest in the S phase at different stages of DNA replication, as well as with different timing of induced p21( Waf1) expression. Thus, cells grown in serum, express elevated p21(Waf1) pr otein levels after 4 hr, whereas serum-deprived, differentiated cells, only after 24 hr, The mRNA levels of p21(Waf1) follow a similar timed pattern. Hence p21(Waf1) may protect OLN 93 cells against the genotoxic effect of H2 O2, The data suggest an intimate relationship between G1-arrest, morphologi cal differentiation, and H2O2-mediated apoptosis. (C) 1999 Wiley-Liss, Inc.