VP-16-induced nucleotide pool changes and poly(ADP-ribose) synthesis: The role of VP-16 in interphase death
1989; Elsevier BV; Volume: 185; Issue: 1 Linguagem: Inglês
10.1016/0014-4827(89)90052-9
ISSN1090-2422
AutoresAkihiko Tanizawa, Masaru Kubota, Hisako Hashimoto, Tsunehiro Shimizu, Tetsuya Takimoto, Toshiyuki Kitoh, Yuichi Akiyama, Harukí Mikawa,
Tópico(s)Calcium signaling and nucleotide metabolism
ResumoExposure of human promyelocytic leukemia cell line (HL-60) to VP-16 resulted in accumulation of DNA strand breaks. Concomitantly, intracellular NAD levels fell at 1 h, followed by declines in ATP at 2 h and in GTP, CTP, and UTP at 3 h. Furthermore, marked morphological changes, such as loss of microvilli or bleb formation, appeared at 4 h and cell death by 8–10 h. The addition of an inhibitor of poly(ADP-ribose) polymerase, 3-aminobenzamide (5 mM), theophylline (2 mM), or thymidine (1 mM), prevented these sequential reductions of nucleotide pools and cell death. In fact, the activation of poly(ADP-ribose) synthesis was detectable within a few hours after treatment with VP-16, although it was smaller than that induced by N-methyl-N′-nitro-N-nitrosoguanidine. These results may suggest the possible role of activation of poly(ADP-ribosyl)ation in VP-16-induced nucleotide pool changes and subsequent interphase death.
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