Mechanism of Hoechst 33342-induced apoptosis in BC3H-1 myocytes.
Hoechst 33342, a bisbenzimidazole dye, binds to adenine/thymine rich regions in the minor groove of deoxyribonucleic acid (DNA). This dye induces apoptosis in BC3H-1 myocytes. The mechanism of Hoechst 33342-induced apoptosis was investigated. Inhibitors of ribonucleic acid (RNA) synthesis, protein synthesis, and serine or cysteine proteases failed to prevent BC3H-1 myocyte death induced by Hoechst 33342. Apoptosis may be dependent on increased p53 expression. Hoechst 33342 had no effect on p53 expression in BC3H-1 myocytes. Lactate oxidation, a monitor of mitochondrial function, was altered by Hoechst 33342 in dose dependent manner. Also, nuclear extracts were used to assay endogenous topoisomerase I activity which was inhibited by Hoechst 33342 treatment of BC3H-1 myocytes. Therefore, Hoechst 33342 appears to initiate apoptosis in BC3H-1 myocytes by a pathway which is independent of de novo RNA and protein synthesis. However, the dye does initiate mitochondrial dysfunction and inhibition of nuclear topoisomerase I as two important steps in the apoptotic pathway.
Zhang
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Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Kiechle
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D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000494:pharmacology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53 / Q000235:genetics; D051379:Mice; D009132:Muscles / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D011480:Protease Inhibitors; D011500:Protein Synthesis Inhibitors; D059004:Topoisomerase I Inhibitors; D003609:Dactinomycin; D003513:Cycloheximide; C017807:bisbenzimide ethoxide trihydrochloride