title: Se-methylselenocysteine inhibits apoptosis induced by clusterin knockdown in neuroblastoma N2a and SH-SY5Y cell lines.
abstract: Apoptosis, as a programmed cell death process, is essential for the maintenance of tissue function in organisms. Alteration of this process is linked to many diseases. Over-expression of clusterin (Clu) can antagonize apoptosis in various cells. Selenium (Se) is an essential trace element for human health. Its biological function is also associated with cell apoptosis. To explore the function of Clu and the impact of Se in the process of apoptosis, several short-hairpin RNAs (shRNA) were designed for the construction of two sets of recombinant plasmids: one set for plasmid-transfection of mouse neuroblastoma N2a cells (N2a cells); and the other set for lentiviral infection of human neuroblastoma SH-SY5Y cells (SH-SY5Y cells). These shRNAs specifically and efficiently interfered with the intracellular expression of Clu at both the mRNA and protein levels. The Clu-knockdown cells showed apoptosis-related features, including down-regulation of antioxidative capacity and the Bcl-2/Bax ratio and up-regulation of caspase-8 activity. Se-methylselenocysteine (MSC) at an optimum concentration of 1 μM could reverse the alteration in antioxidative capacity, Bcl2/Bax ratio and caspase-8 activity caused by Clu-knockdown, thus inhibiting apoptosis and maintaining cell viability. The results hereby imply the potentiality of Clu and Se in neuroprotection.
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. raulw2003@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences, Shenzhen University, Shenzhen 518060, China. tim@alevel.com.cn.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences, Shenzhen University, Shenzhen 518060, China. liuqiong@szu.edu.cn.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Microorganism Examination Division, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China. renlizhangszcdc@aliyun.com.
authors.forename: Renli
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. jzni@szu.edu.cn.
authors.forename: Jiazuan
authors.initials: J
authors.lastname: Ni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D051152:Clusterin / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012643:Selenium / Q000378:metabolism; D017279:Selenocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051152:Clusterin; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D017279:Selenocysteine; D053181:Caspase 8; D012643:Selenium; C002979:selenomethylselenocysteine