Nitric oxide donor-induced p53-sensitive cell death is enhanced by Bcl-2 reduction in human neuroblastoma cells

Neurochem Int. 1998 Jan;32(1):93-102. doi: 10.1016/s0197-0186(97)00029-6.

Abstract

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 pretreatment for 4 days with N6,2'-O-dibutyryl cyclic AMP (diBu-cAMP) or staurosporine, while those were not changed by pretreatment with phorbol 12-myristate 13-acetate (PMA). Protein level of Bcl-2 was decreased by pretreatment with diBu-cAMP or staurosporine, and, on the contrary, the level was increased by pretreatment with PMA. However, these pretreatments did not change Bax protein level and SNAP-induced p53 expression. However, SNAP-treatment did not change protein levels of Bcl-2 and Bax. These results suggest that SNAP-induced p53-sensitive apoptosis is enhanced by Bcl-2 reduction, and that Bcl-2 and Bax may act downstream of p53 in SH-SY5Y cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bucladesine / pharmacology
  • Cell Death / drug effects*
  • DNA Fragmentation
  • Dimerization
  • Gene Expression
  • Genes, p53 / genetics
  • Humans
  • Immunohistochemistry
  • Mice
  • Neuroblastoma / metabolism*
  • Neuroblastoma / ultrastructure
  • Nitric Oxide / metabolism*
  • Oxidation-Reduction
  • Penicillamine / analogs & derivatives*
  • Penicillamine / pharmacology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • S-Nitroso-N-Acetylpenicillamine
  • Staurosporine / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / physiology*
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Bax protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Nitric Oxide
  • Bucladesine
  • S-Nitroso-N-Acetylpenicillamine
  • Penicillamine
  • Staurosporine
  • Tetradecanoylphorbol Acetate