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TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.

Publication ,  Journal Article
Sosna, J; Voigt, S; Mathieu, S; Lange, A; Thon, L; Davarnia, P; Herdegen, T; Linkermann, A; Rittger, A; Chan, FK-M; Kabelitz, D; Schütze, S; Adam, D
Published in: Cell Mol Life Sci
January 2014

Programmed necrosis is important in many (patho)physiological settings. For specific therapeutic intervention, however, a better knowledge is required whether necrosis occurs through one single "core program" or through several independent pathways. Previously, the poly(ADP-ribose) polymerase (PARP) pathway has been suggested as a crucial element of tumor necrosis factor (TNF)-mediated necroptosis. Here, we show that TNF-induced necroptosis and the PARP pathway represent distinct and independent routes to programmed necrosis. First, DNA-alkylating agents such as 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) or methyl methanesulfonate rapidly activate the PARP pathway, whereas this is a late and secondary event in TNF-induced necroptosis. Second, inhibition of the PARP pathway does not protect against TNF-induced necroptosis, e.g., the PARP-1 inhibitor 3-AB prevented MNNG- but not TNF-induced adenosine-5'-triposphate depletion, translocation of apoptosis-inducing factor, and necrosis. Likewise, olaparib, a more potent and selective PARP-1 inhibitor failed to block TNF-induced necroptosis, identical to knockdown/knockout of PARP-1, pharmacologic and genetic interference with c-Jun N-terminal kinases and calpain/cathepsin proteases as further components of the PARP pathway. Third, interruption of TNF-induced necroptosis by interference with ceramide generation, RIP1 or RIP3 function or by the radical scavenger butylated hydroxyanisole did not prevent programmed necrosis through the PARP pathway. In summary, our results suggest that the currently established role of the PARP pathway in TNF-induced necroptosis needs to be revised, with consequences for the design of future therapeutic strategies.

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Published In

Cell Mol Life Sci

DOI

EISSN

1420-9071

Publication Date

January 2014

Volume

71

Issue

2

Start / End Page

331 / 348

Location

Switzerland

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • RNA-Binding Proteins
  • RNA, Small Interfering
  • RNA Interference
  • Poly(ADP-ribose) Polymerases
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Piperazines
  • Phthalazines
  • Nuclear Pore Complex Proteins
 

Citation

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Sosna, J., Voigt, S., Mathieu, S., Lange, A., Thon, L., Davarnia, P., … Adam, D. (2014). TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death. Cell Mol Life Sci, 71(2), 331–348. https://doi.org/10.1007/s00018-013-1381-6
Sosna, Justyna, Susann Voigt, Sabine Mathieu, Arne Lange, Lutz Thon, Parvin Davarnia, Thomas Herdegen, et al. “TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.Cell Mol Life Sci 71, no. 2 (January 2014): 331–48. https://doi.org/10.1007/s00018-013-1381-6.
Sosna J, Voigt S, Mathieu S, Lange A, Thon L, Davarnia P, et al. TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death. Cell Mol Life Sci. 2014 Jan;71(2):331–48.
Sosna, Justyna, et al. “TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.Cell Mol Life Sci, vol. 71, no. 2, Jan. 2014, pp. 331–48. Pubmed, doi:10.1007/s00018-013-1381-6.
Sosna J, Voigt S, Mathieu S, Lange A, Thon L, Davarnia P, Herdegen T, Linkermann A, Rittger A, Chan FK-M, Kabelitz D, Schütze S, Adam D. TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death. Cell Mol Life Sci. 2014 Jan;71(2):331–348.
Journal cover image

Published In

Cell Mol Life Sci

DOI

EISSN

1420-9071

Publication Date

January 2014

Volume

71

Issue

2

Start / End Page

331 / 348

Location

Switzerland

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • RNA-Binding Proteins
  • RNA, Small Interfering
  • RNA Interference
  • Poly(ADP-ribose) Polymerases
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Piperazines
  • Phthalazines
  • Nuclear Pore Complex Proteins