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Int. J. Mol. Sci. 2016, 17(10), 1678; doi:10.3390/ijms17101678

Induction of Apoptosis in TNF-Treated L929 Cells in the Presence of Necrostatin-1

Department of Internal Medicine, Osaka Dental University, Hirakata 573-1121, Japan
Academic Editors: Anthony Lemarié and William Chi-shing Cho
Received: 3 August 2016 / Revised: 9 September 2016 / Accepted: 27 September 2016 / Published: 7 October 2016
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
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Abstract

It 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
Keywords: apoptosis; necroptosis; TNF; L929 cells; caspase-3; caspase-8; Z-VAD-fmk; Z-Asp-CH2-DCB apoptosis; necroptosis; TNF; L929 cells; caspase-3; caspase-8; Z-VAD-fmk; Z-Asp-CH2-DCB
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MDPI and ACS Style

Sawai, H. Induction of Apoptosis in TNF-Treated L929 Cells in the Presence of Necrostatin-1. Int. J. Mol. Sci. 2016, 17, 1678.

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