The Function Of 15KD Selenoprotein In Endoplasmic Reticulum Stress And Differential Proteomics Related To Endoplasmic Reticulum Stress

Selenium is an essential trace element in human, and associated with many diseases.15 KD selenoprotein(Sep 15) is one of the endoplasmic reticulum lumen located selenoproteinmembers. Its NMR analysis indicated that like the other members,Sep15 also has the ability to regulate redox. The existing research results show that, thecysteine-rich domain of Sep15 has an established function to mediate the formation of a high affinity 1:1 complex between Sep15 and the folding sensor of the calnexin cycle-UDP-glucose:glycoprotein glucosyltransferase(UGGT),so that it can reside in the endoplasmic reticulum, thus Sep15 may be involved in protein folding and N-glycosylated modification process in the endoplasmic reticulum. As a primary place for protein folding and processing,steady maintaining of endoplasmic reticulum is quite important to exert normal physiological activities of cells. Conversely, under external stimuli(such as heat shock, high pressure, etc.) or pathological conditions(such as redox imbalance, Ca2+ imbalance, etc.), the steady-state will be disrupted.The influence of external or internal factorswill lead to endoplasmic reticulum stress(ERS), resulting in unfolding or Misfolded proteins stacked in the ER.Endoplasmic reticulum protection activated UPR reaction to protect cell from damage caused by ERS and restore cell functions. However, with excessive accumulation of unfolding or misfolded proteins, as well as further inbalance of the steady state, UPR will not repair cell damage whivh leadto irreversible cell apoptosis. Studies have found, Sep15 has very close linkswith ERS. Sep15 expressionwill be affected by the different regulation of ERS. The cause of Sep15 protein expression changes is still unknown.The study revealed the expression of Sep15 under ERS by different inducers.In adaptive ERSinduced by Tunicamycin, Sep15 increased gradually depend on the drug concentration; Meanwhile, the level of UGGT also increased gradually; ERS signaling pathway associated proteins Bip, Chop, Caspase12 levels increased as well, while JNK activated just in a short time. In DTT-induced ERS,Sep15 downregulated in a concentration and time-dependent way, UGGT could not rise when Sep15 dropped to a certain level; Bip reduced just like Sep15, while chop, Caspase12 and JNK are activated. Thus, Sep15 and ER chaperone Bip expression are highly consistent, and the different regulation of Sep15 by ERS maybe related with the activation of JNK. In addition, we did differential proteomic analysis under different ERS. It is found that ERS induced by Tm can cause the decreasing level of cytoskeletal proteins, like TBB4, BENAH, KAD1, PAK4, RM11, ACTC, which may affect cytoskeleton, migration and signal transduction in neurons; DTT-induced ERS reduced expression of protein isomerase, like DOPD, PMM2, FKBP4, PPIA; oxidative phosphorylation related proteins ATPB, NDUA4, QCR2, ATPO, NDUS8, QCR8's expression disordered; ubiquitin protein degradation pathway was inhibited by decreasing expression of ubiquitin-related proteins, such as UBA1, ELOB, SAR1 B, UBC12, PML, SKP1.