trx2在斑马鱼肝脏发育中的功能分析.docx

trx2在斑马鱼肝脏发育中的功能分析方法，在体内和体外试验中发觉，肝脏细胞死亡的发生和GAPDH硝基化增多有关，我们在HepG2细胞中的试验结果进一步表明，GAPDH的硝基化增多会引起更多的GAPDIl入核并且导致p53活性位点IyS乙酰化增多。活化的p53起始卜.游bax和PUma基因表达增加。bax和puma是线粒体促凋亡基因，它们的发达失调可能和肝脏细胞死亡发生有关。在斑马鱼中我们同样发觉morphIino敲低Trx2后bax和PUma表达量同样上升。至此，我们提出了一个可能的新的TrX2导致凋亡的机制，这种机制提示了Trx2在早期肝脏器官发育过程中可能起重要功能。关键词：Trx2：肝脏发育：硝基化修饰：GAPDH；p53乙酰化：细胞死亡HI万方数据AbstractThioredoxins(Trxs)maintainthebalanceofcellularredoxstatustopreventcellsfromoxidativestressesandalsohaveacrucialroleintheapoptosis,neuroprotectionandinfIammatoryreaction.AllTrxshaveacanonicalCXXCcatalyticmotifandreducesubstrateproteinswiththeactionofNAPDlIandTrxR.Proteinde-nitrosylationandtrans-nitrosyIationbycytosolicandmitochondrialTrxswereproposedinrecentreport.Trx2isaredoxproteinlocatedinmitochondria.MitochondriaaretheenergyfactoriesofthecellsandElectrontransferandoxidativephosphorylationoccurinmitochondria.Oxidativestresscaninduceapoptosisbythereleaseofcytochromecandotherapoptoticfactorsfromthemitochondria.Alossofthemitochondrialmembranepotentialwillinducecelldeathirreversibly.So,normamitochondrialfunctionisessentialtocellgrowth.Trx2playsanessentialroleinscavengingincreasedROS(reactiveoxygenspecies)inmitochondria.Theanti-apoptoticfunctionofTrx2hasbeenpersistentlyfocusingon.OverexpressionofTrx2in143BcellsprotectagainstTBH(tertbutylIiydroperoxide)-inducedcel1cytotoxicity.InhumanHEK-293cells.Trx2canprotectcellsfrometoposide-inducedcelldeathandincreasedmiIochondrialmembranepotential.Trx2conditionalknockoutinchickenDT40cellcausedanelevatedROSlevelsandapoptosis.1.ittleisknownaboutthecontributionofTrx2duringembryogenesis.