Induction of Apoptosis in TNF-Treated L929 Cells in the Presence of Necrostatin-1
AbstractIt has been shown that necroptosis—caspase-independent programmed necrotic cell death—can be induced by treatment with tumor necrosis factor (TNF) in the L929 murine fibrosarcoma cell line, even in the absence of a caspase inhibitor. Although it was reported that necrostatin-1—a specific inhibitor of necroptosis—inhibited TNF-induced necroptosis in L929 cells, it has not been elucidated whether the cells eventually die by apoptosis in the presence of necrostatin-1. In this paper, induction of apoptosis was demonstrated in TNF-treated L929 cells in the presence of necrostatin-1. Co-treatment with cycloheximide expedited apoptosis induction in necrostatin-1/TNF-treated L929 cells: typical apoptotic morphological changes, including membrane blebbing and nuclear fragmentation, induction of caspase-3 activity, proteolytic activation of caspases-3, -8, and -9, and cleavage of poly(ADP-ribose) polymerase (PARP) (a well-known substrate of caspase-3) were observed. Moreover, co-treatment with Z-VAD-fmk (a pan-caspase inhibitor) inhibited apoptosis by completely inhibiting caspases, resulting in a shift from apoptosis to necroptosis. In contrast, co-treatment with Z-Asp-CH2-DCB (a caspase inhibitor preferential to caspase-3) inhibited apoptosis without expediting necroptosis. These results indicate that apoptosis can be induced in TNF-treated L929 cells when the cells are protected from necroptosis, and support the notion that partial activation of caspase-8 in the presence of a caspase inhibitor preferential to caspase-3 suppresses both apoptosis and necroptosis. View Full-Text
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Sawai, H. Induction of Apoptosis in TNF-Treated L929 Cells in the Presence of Necrostatin-1. Int. J. Mol. Sci. 2016, 17, 1678.
Sawai H. Induction of Apoptosis in TNF-Treated L929 Cells in the Presence of Necrostatin-1. International Journal of Molecular Sciences. 2016; 17(10):1678.Chicago/Turabian Style
Sawai, Hirofumi. 2016. "Induction of Apoptosis in TNF-Treated L929 Cells in the Presence of Necrostatin-1." Int. J. Mol. Sci. 17, no. 10: 1678.
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