Abstract

Unfolded protein response (UPR) is a signaling pathway originating from endoplasmic reticulum (ER). UPR activates upon aggregation of unfolded proteins within ER lumen (known as ER stress), and is mediated through three ER membrane anchored proteins. UPR causes either survival or apoptosis of underlying cells. Wide range of UPR triggering conditions has been studied including oxidative stress. However, the role of oxidative stress on UPR activity is somehow controversial. We evaluated if oxidative stress could potentially suppress UPR activation in specific conditions. Multiple cellular stress categories were designed using different combinations of hydrogen peroxide (H2O2), Tunicamycin(Tm) and Thapsigargin (Tg).Then, expression of UPR target genes, Grp94 and Gadd153, assessed by real time PCR. We observed that the expression of UPR target genes was modified by oxidative stress depending on oxidative stress timing of induction. Simultaneous and especially previous association of oxidative stress with ER stress inhibited UPR target genes expression in a variable manner. However, exposure to oxidative stress after induction of ER stress showed a different partial-suppressive gene expression pattern. We also observed that preferential expression of apoptotic (Gadd153) gene could be resulted from ER/oxidative stress interaction. Suppressing effect of oxidative stress on expression of UPR target genes in combinational states with ER stress may partly explain the pathology of diseases which are associated with both oxidative and ER stress but unable to respond appropriately by activating UPR.