Naslov
Effect of UVC radiation on mouse fibroblasts deficient for FAS-associated protein with death domain

Autori
Begović, Lidija ; Antunović, Maja ; Matić, Igor ; Furčić, Ivana ; Baričević, Ana ; Vojvoda Parčina, Valerija ; Peharec Štefanić, Petra ; Nagy, Biserka ; Marijanović, Inga

Izvornik
International journal of radiation biology (0955-3002) 92 (2016), 8; 475-482

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

Ključne riječi
Apoptosis ; FADD ; mouse embryonic fibroblasts ; necrosis ; UVC radiation
(Apoptosis ; FADD ; mouse embryonic fibroblasts ; necrosis ; UVC radiatio)

Sažetak
Purpose: Ultraviolet (UV) radiation-induced apoptosis enabled us to study the mechanism of DNA damage and to investigate how cells avoid consequences of damaged DNA. Cells with extensive DNA damage activate extrinsic and intrinsic pathways of apoptosis. The extrinsic pathway is coupled to a FAS-associated protein with death domain (FADD), an adaptor protein molecule necessary for mediating apoptotic signals through the cell. Materials and methods: Viability and apoptosis of wild-type and FADD-deficient mouse embryonic fibroblasts were investigated 1, 3, 24 and 48 h after exposure to three doses (50, 75 and 300 J/m2) of UVC radiation. Morphological changes were observed using DNA binding dyes (Hoechst and propidium iodide) while biochemical changes were monitored using immunodetection of the poly (ADP-ribose)polymerase (PARP) protein cleavage and caspase-3 activity assay.Results: Results showed that the difference in cell death response between wild-type and FADDdeficient cells depended on dose and incubation time after exposure to UVC radiation. FADD-deficient cells are more sensitive to UVC radiation. Even though FADD- deficient cells lack an adapter protein of apoptotic extrinsic pathway, higher doses of UVC triggered their apoptotic response, while wild-type cells die mainly due to necrosis. A different pattern of caspase 3 activity and PARP cleavage was observed 24 h after radiation between two cell lines confirming higher apoptotic response in FADD-deficient cells. Conclusions: Wild-type cells can execute apoptosis via both, the mitochondrial and the receptormediated pathway whereas FADD-deficient cells can only activate the intrinsic pathway. There is a difference in UVC radiation response between two cell lines indicating the role of FADD in the selection of cell death modality.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA