c-myc is not involved in cadmium-elicited apoptotic pathway in porcine kidney LLC-PK1 cells.
Cadmium chloride can induce DNA fragmentation, a biochemical characteristics of apoptosis in renal epithelial LLC-PK1 cells. Studies of cadmium cytotoxicity demonstrated that cadmium activates c-myc transcription. In this study, we investigated whether c-myc is a necessary component of cadmium-induced apoptosis. By kinetic analysis, transient activation of c-myc transcript by cadmium occurred before DNA fragmentation was induced by the metal, indicating an apparent correlation between induction of c-myc mRNA and promotion of apoptosis. However, even when using actinomycin D to block transcriptional activation of c-myc, or antisense oligodeoxynucleotide complementary to c-myc to block translation of c-myc, cadmium could still induce apoptosis. Thus, our data show that cadmium elicits apoptosis by a mechanism other than regulation of c-myc expression: transcriptional activation of c-myc during apoptosis is not always involved in the cell-death events.
Environmental Health Sciences Division, National Institute for Environmental Studies, Onogawa, Tsukuba, Japan.
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M
Ishido
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C
Tohyama
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T
Suzuki
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D003609:Dactinomycin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018374:LLC-PK1 Cells; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D015032:Zinc / Q000494:pharmacology
D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D002104:Cadmium; D003609:Dactinomycin; D015032:Zinc