Naslov
FADD-deficient mouse embryonic fibroblasts undergo RIPK1-dependent apoptosis and autophagy after NB-UVB irradiation

Autori
Antunovic, Maja ; Matic, Igor ; Nagy, Biserka ; Caput Mihalic, Katarina ; Skelin, Josipa ; Stambuk, Jerko ; Josipovic, Pavle ; Dzinic, Tamara ; Paradzik, Mladen ; Marijanovic, Inga

Izvornik
Journal of photochemistry and photobiology. B, Biology (1011-1344) 194 (2019); 32-45

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
FADD NB-UVB irradiation Cell death inhibitors RIPK1-dependent apoptosis Autophagy

Sažetak
Sun or therapy-related ultraviolet B (UVB) irradiation induces different cell death modalities such as apoptosis, necrosis/necroptosis and autophagy. Understanding of mechanisms implicated in regulation and execution of cell death program is imperative for prevention and treatment of skin diseases. An essential component of death-inducing complex is Fas-associated protein with death domain (FADD), involved in conduction of death signals of different death modalities. The purpose of this study was to enlighten the role of FADD in the selection of cell death mode after narrow-band UVB (NB-UVB) irradiation using specific cell death inhibitors (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (zVAD-fmk), Necrostatin-1 and 3-Methyladenine) and FADD-deficient (FADD−/−) mouse embryonic fibroblasts (MEFs) and their wild type (wt) counterparts. The results imply that lack of FADD sensitized MEFs to induction of receptor–interacting protein 1 (RIPK1)-dependent apoptosis by the generation of reactive oxygen species (ROS), but without activation of the proteins p53, Bax and Bcl-2 as well as without the enrolment of calpain-2. Autophagy was established as a contributing factor to NB-UVB-induced death execution. By contrast, wt cells triggered intrinsic apoptotic pathway that was resistant to the inhibition by zVAD-fmk and Necrostatin-1 pointing to the mechanism overcoming the cell survival. These findings support the role of FADD in prevention of autophagy-dependent apoptosis.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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