SESN2/NRF2 signaling activates as a direct downstream regulator of the PERK pathway against endoplasmic reticulum stress to improve the in vitro maturation of porcine oocytes

Free Radic Biol Med. 2021 Dec 16:S0891-5849(21)01110-2. doi: 10.1016/j.freeradbiomed.2021.12.258. Online ahead of print.ABSTRACTNuclear erythroid 2-related factor 2 (NRF2) is a critical regulator of oxidative stress in mammalian oocytes. Our previous study described the protective effects of Sestrin-2 (SESN2) as a stress regulator against endoplasmic reticulum (ER) stress in porcine oocytes during in vitro maturation (IVM). However, their roles in unfolded protein response-related signaling pathways in porcine oocyte maturation capacity remain unknown. The purpose of this study was to evaluate the role of SESN2/NRF2 signaling in H2O2-induced oxidative stress and ER stress via protein kinase-like ER kinase (PERK) downstream factor during porcine oocyte maturation. Here, we found that the p-NRF2(Ser40) activation in the nucleus of porcine oocytes was accompanied by PERK signaling downregulation using western blot and immunofluorescence staining at 44 h after IVM. The total and nuclear NRF2 protein expression was also induced in porcine oocytes following H2O2 and tunicamycin (Tm) exposure. Notably, the upregulation of PERK signaling significantly increased the SESN2 and NRF2 signaling in H2O2-and Tm-exposed porcine cumulus oocyte complexes. Interestingly, inducing the knockdown of the SESN2 gene expression by siRNA interrupted the NRF2 signaling activation of porcine oocyte maturation, whereas NRF2 expression blockade by ochratoxin A, an NRF2 inhibitor, did not affect the expres...

Source: Free Radical Biology and Medicine - December 19, 2021 Category: Biology Authors: Hyo-Jin Park Seul-Gi Yang Deog-Bon Koo Source Type: research