2016
Sulforaphane-induced apoptosis involves the type 1 IP3 receptor
HUDECOVA, Sona, Jana MARKOVA, Veronika SIMKO, Lucia CSADEROVA, Tibor STRAČINA et. al.Základní údaje
Originální název
Sulforaphane-induced apoptosis involves the type 1 IP3 receptor
Autoři
HUDECOVA, Sona (703 Slovensko), Jana MARKOVA (703 Slovensko), Veronika SIMKO (703 Slovensko), Lucia CSADEROVA (703 Slovensko), Tibor STRAČINA (703 Slovensko, domácí), Marta SIROVA (703 Slovensko), Michaela FOJTŮ (203 Česká republika, domácí), Eliska SVASTOVA (703 Slovensko), Paulina GRONESOVA (703 Slovensko), Michal PASTOREK (703 Slovensko), Marie NOVÁKOVÁ (203 Česká republika, garant, domácí), Dana CHOLUJOVA (703 Slovensko), Juraj KOPACEK (703 Slovensko), Silvia PASTOREKOVA (703 Slovensko), Jan SEDLAK (703 Slovensko) a Olga KRIZANOVA (703 Slovensko)
Vydání
Oncotarget, Albany, Impact Journals LLC, 2016, 1949-2553
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30105 Physiology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 5.168
Kód RIV
RIV/00216224:14110/16:00091552
Organizační jednotka
Lékařská fakulta
UT WoS
000387164700045
Klíčová slova anglicky
type 1 IP3 receptor; sulforaphane; apoptosis. NRF2; nude mice
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 10. 1. 2017 10:54, Ing. Mgr. Věra Pospíšilíková
Anotace
V originále
In this study we show that anti-tumor effect of sulforaphane (SFN) is partially realized through the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). This effect was verified in vitro on three different stable cell lines and also in vivo on the model of nude mice with developed tumors. Early response (6 hours) of A2780 ovarian carcinoma cells to SFN treatment involves generation of mitochondrial ROS and increased transcription of NRF2 and its downstream regulated genes including heme oxygenase 1, NAD(P)H:quinine oxidoreductase 1, and KLF9. Prolonged SFN treatment (24 hours) upregulated expression of NRF2 and IP3R1. SFN induces a time-dependent phosphorylation wave of HSP27. Use of IP3R inhibitor Xestospongin C (Xest) attenuates both SFN-induced apoptosis and the level of NRF2 protein expression. In addition, Xest partially attenuates anti-tumor effect of SFN in vivo. SFN-induced apoptosis is completely inhibited by silencing of IP3R1 gene but only partially blocked by silencing of NRF2; silencing of IP3R2 and IP3R3 had no effect on these cells. Xest inhibitor does not significantly modify SFN-induced increase in the rapid activity of ARE and AP1 responsive elements. We found that Xest effectively reverses the SFN-dependent increase of nuclear content and decrease of reticular calcium content. In addition, immunofluorescent staining with IP3R1 antibody revealed that SFN treatment induces translocation of IP3R1 to the nucleus. Our results clearly show that IP3R1 is involved in SFN-induced apoptosis through the depletion of reticular calcium and modulation of transcription factors through nuclear calcium up-regulation.