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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bucladesine / pharmacology
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Cell Death / drug effects*
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DNA Fragmentation
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Dimerization
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Gene Expression
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Genes, p53 / genetics
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Humans
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Immunohistochemistry
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Mice
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Neuroblastoma / metabolism*
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Neuroblastoma / ultrastructure
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Nitric Oxide / metabolism*
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Oxidation-Reduction
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Penicillamine / analogs & derivatives*
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Penicillamine / pharmacology
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / analysis
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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S-Nitroso-N-Acetylpenicillamine
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Staurosporine / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / analysis
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Tumor Suppressor Protein p53 / physiology*
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bcl-2-Associated X Protein
Substances
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BAX protein, human
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Bax protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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Nitric Oxide
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Bucladesine
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S-Nitroso-N-Acetylpenicillamine
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Penicillamine
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Staurosporine
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Tetradecanoylphorbol Acetate