NITRIC-OXIDE DONOR-INDUCED P53-SENSITIVE CELL-DEATH IS ENHANCED BY BCL-2 REDUCTION IN HUMAN NEUROBLASTOMA-CELLS

In human neuroblastoma SH-SY5Y cells, S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO)-donor, caused cell death accompanying p53 expression, nucleosomal DNA fragmentation and cell death. In addition, SNAP-induced cell death and DNA fragmentation were enhanced by pretre atment for 4 days with N-6,2'-O-dibutyryl cyclic AMP (diBu-cAMP) or st aurosporine, while those were not changed by pretreatment with phorbol 12-myristate 13-acetate (PMA). Protein level of Bcl-2 was decreased b y pretreatment with diBu-cAMP or staurosporine, and, on the contrary, the level was increased by pretreatment with PMA. However, these pretr eatments did not change Bax protein level and SNAP-induced p53 express ion. However, SNAP-treatment did not change protein levels of Bcl-2 an d Bax. These results suggest that SNAP-induced p53-sensitive apoptosis is enhanced by Bcl-2 reduction, and that Bcl-2 and Bax may act downst ream of p53 in SH-SY5Y cells. (C) 1998 Elsevier Science Ltd. All right s reserved.