Hydrogen peroxide induces nuclear translocation of p53 and apoptosis in cells of oligodendroglia origin

The observation that apoptosis is an inherent pathway in oligodendrocytes d evelopment coupled with the notion that wild-type p53 is expressed in these cells, prompted us to investigate the interrelationship between the two ph enomena. Using a permanent oligodendroglia-like cell line (OLN 93), we exam ined the role of p53 protein in apoptosis following a DNA insult induced by a brief exposure to H2O2. A marked translocation of p53 from the cytosolic to the nuclear compartment was notable by 20 min, following a 5 min treatm ent with 1 mM H2O2 as identified by cell immunostaining. By 48 h following H2O2 addition, nearly 60% of the cells exhibited p53 in the nuclei. At this time, a large proportion of the cells underwent apoptosis as identified by DAPI nuclear staining. The genotoxic-induced p53 relocalization appeared t o be cell cycle phase specific; thus OLN 93 cultures enriched for cells in the G(0)/G(1) stage by serum starvation, and abundant in nuclear-associated p53, were more susceptible to H2O2-induced apoptosis than their untreated counterparts and than double thymidine block, G(1)/S enriched, cultures. An alysis of the expression of p53 downstream genes indicated that p21 and mdm 2 were upregulated following p53 nuclear translocation. From the kinetics o f protein accumulation, it appears that mdm2 enhancement accelerated the ex it of p53 from the nucleus to the cytosol. Our results suggest that followi ng stress, oligodendroglia-like cells are induced to undergo p53-dependent apoptosis, an event that coincides with p53 nuclear translocation and is ce ll-cycle related. (C) 1999 Elsevier Science B.V. All rights reserved.