Hoechst 33342 induces apoptosis and alters tata box binding protein/DNA complexes in nuclei from BC3H-1 myocytes.
Hoechst 33342 and Hoechst 33258 bind to adenine-thymine rich regions of the minor groove of DNA. Hoechst 33342, but not Hoechst 33258, induces BC3H-1 myocyte cell death and DNA fragmentation into an internucleosomal pattern characteristics of apoptosis. Hoechst 33342 has been shown to inhibit endogenous nuclear topoisomerase I activity. Another enzymatic activity utilizing the minor groove of DNA, the initiation of RNA polymerase II activity by formation of a TATA box binding protein/TATA box promoter complex, is shown to be altered using a gel mobility shift assay. A [32P]-labeled 24-oligonucleotide containing a TATA box element formed one molecular weight complex in control and Hoechst 33258 treated cells. The presence of Hoechst 33342 (26.7 microM) decreased the amount of the control complex and increased the presence of lower molecular weight species suggesting degradation of nuclear TBP and/or release of other transcription factors from the complex creating a smaller sized molecular complex which retains TATA box binding capacity. These results suggest that the pathway utilized to induce apoptosis in BC3H-1 myocytes may also involve the alteration of normal TBP/DNA complex formation and reduction in the initiation of new transcription.
Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, Michigan 48073-6769, USA.
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D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000494:pharmacology*; D006690:Bisbenzimidazole / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051379:Mice; D009132:Muscles / Q000166:cytology* / Q000187:drug effects; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism*
D001562:Benzimidazoles; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D004247:DNA; D006690:Bisbenzimidazole; C017807:bisbenzimide ethoxide trihydrochloride