biostudies-literatureUnknown71(2)Sosna JProgrammed 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 protectCellular and molecular life sciences : CMLS331-48https://www.ebi.ac.uk/biostudies/studies/S-EPMC3889832biostudies-literatureTNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.PMC3889832Sosna JKabelitz DLange ALinkermann AVoigt SAdam DMathieu SChan FKDavarnia PRittger ASchutze SThon LHerdegen TfalseTNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.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 protect2014-01-01T00:00:00Z2014 Jan2026-05-07T07:09:06.195Z2019-03-27T01:19:55ZS-EPMC38898322376020510.1007/s00018-013-1381-6