Abstract
Recent studies have proposed that tumor necrosis factor alpha (TNF-alpha) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apoptosis and induced by ionizing radiation, is accompanied by concomitant decreases in Bcl-2 and Bcl-X mRNA levels in HL-60 and U-937 human leukemia cells. Apoptotic DNA fragmentation after exposure to TNF-alpha and C2-ceramide was also associated with down-regulation of Bcl-2 mRNA in HL-60 and U-937 cells, while Bcl-X mRNA production was unaffected. These results suggest that modulation of Bcl-2 gene expression may be a target for ceramide-mediated apoptosis following exposure to ionizing radiation and TNF-alpha. Changes in Bcl-2 expression may be the basis for the interactive killing observed between radiation and TNF-alpha in some human and tumor cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / physiology
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Apoptosis / radiation effects*
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Base Sequence
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Cell Death / drug effects
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Cell Death / physiology
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Ceramides / pharmacology*
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Combined Modality Therapy
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DNA Damage
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DNA, Neoplasm / drug effects
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DNA, Neoplasm / metabolism
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DNA, Neoplasm / radiation effects
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Down-Regulation
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Gene Expression / drug effects
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Gene Expression / radiation effects
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Gene Expression Regulation, Leukemic
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Humans
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Leukemia / drug therapy
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Leukemia / pathology
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Leukemia / radiotherapy
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Molecular Sequence Data
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Proto-Oncogene Proteins / biosynthesis*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger / biosynthesis
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RNA, Messenger / drug effects
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RNA, Messenger / radiation effects
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / radiation effects
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Tumor Necrosis Factor-alpha / pharmacology*
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bcl-X Protein
Substances
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BCL2L1 protein, human
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Ceramides
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DNA, Neoplasm
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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bcl-X Protein