X Box-binding Protein 1 Protects Macrophages From Low-density Lipoprotein-Induced Apoptosis Via Regulating Ubiquitin-fold Modifier 1

Objective In this study,we aimed to elucidate the relationship between XBP1 and Ufm1 and to determine their effect on oxidized low density lipoprotein(ox-LDL)–induced macrophage apoptosis.Methods 1.We first analyzed the expression of XBP1,XBP1 s,Ufm1 in ox-LDL–induced macrophage using real-time quantitative PCR(q RT-PCR)and western blot analysis.Ox-LDL induced macrophage apoptosis was detected by using flow cytometry.2.Subsequently,we treated the lentiviral short hairpin RNA(sh RNA)-mediated XBP1-knockdown,XBP1-overexpressing and Ufm1-overexpressing cell lines with 100 μg/m L ox-LDL for 24 h to determine the roles of XBP1 and Ufm1 and detected apoptosis used flow cytometry.3.Finally,we examined the expression of CHOP,cleaved caspase3 in different cell lines by q RT-PCR and western blot analysis.Results 1.Ox-LDL triggered XBP1,XBP1 s and Ufm1 overexpression and induced apoptosis.2.XBP1 knockdown increased ox-LDL–induced macrophage apoptosis and that apoptosis was attenuated after XBP1,Ufm1 overexpression.Furthermore,Ufm1 was a target of XBP1.3.We also found that CHOP and CHOP-dependent activation of caspase-3 are induced apoptosis when macrophages were treated with 100 μg/mL ox-LDL for 24 h.Conclusions 1.Ox-LDL triggered XBP1,XBP1 s and Ufm1 overexpression and induced apoptosis.2.Ufm1 is regulated by XBP1 and that through this regulation,XBP1 and Ufm1 protect macrophages from ox-LDL–induced apoptosis.3.Ox-LDL induces apoptosis in Raw 264.7 cells through CHOP-dependent activation of caspase-3.