Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles
文献类型：期刊论文
| 作者 | Bao, Peng; Chen, Zheng; Tai, Ren-Zhong; Shen, Han-Ming; Martin, Francis L.; Zhu, Yong-Guan |
| 刊名 | JOURNAL OF PROTEOME RESEARCH
 |
| 出版日期 | 2015-02 |
| 卷号 | 14期号:2页码:1127-1136 |
| 关键词 | chemoprevention self-assembly selenite selenium nanoparticles glycolysis mitochondrial dysfuntion tubulin heat shock proteins |
| 英文摘要 | Selenite has been a touted cancer chemopreventative agent but generates conflicting outcomes. Multiple mechanisms of selenite cytotoxicity in cancer cells are thought to be induced by metabolites of selenite. We observed that intracellular metabolism of selenite generates endogenous selenium nanoparticles (SeNPs) in cancer cells. Critical proteins that bind with high affinity to elemental selenium during SeNPs self-assembly were identified through proteomics analysis; these include glycolytic enzymes, insoluble tubulin, and heat shock proteins 90 (HSP90). Sequestration of glycolytic enzymes by SeNPs dramatically inhibits ATP generation, which leads to functional and structural disruption of mitochondria. Transcriptome sequencing showed tremendous down-regulation of mitochondrial respiratory NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and ATP synthase (complex V) in response to glycolysis-dependent mitochondrial dysfunction. Sequestration of insoluble tubulin led to microtubule depolymerization, altering microtubule dynamics. HSP90 sequestration led to degradation of its downstream effectors via autophagy, ultimately resulting in a cell-signaling switch to apoptosis. Additionally, the surface effects of SeNPs generated oxidative stress, thus contributing to selenite cytotoxicity. Herein, we reveal that the multiple mechanisms of selenite-induced cytotoxicity are caused by endogenous protein-assisted self-assembly of SeNPs and suggest that endogenous SeNPs could potentially be the primary cause of selenite-induced cytotoxicity. |
| 研究领域[WOS] | Biochemical Research Methods |
| WOS记录号 | WOS:000349276400048 |
| 公开日期 | 2016-03-08 |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/32374]  |
| 专题 | 生态环境研究中心_城市与区域生态国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Bao, Peng,Chen, Zheng,Tai, Ren-Zhong,et al. Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles[J]. JOURNAL OF PROTEOME RESEARCH,2015,14(2):1127-1136. |
| APA | Bao, Peng,Chen, Zheng,Tai, Ren-Zhong,Shen, Han-Ming,Martin, Francis L.,&Zhu, Yong-Guan.(2015).Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles.JOURNAL OF PROTEOME RESEARCH,14(2),1127-1136. |
| MLA | Bao, Peng,et al."Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles".JOURNAL OF PROTEOME RESEARCH 14.2(2015):1127-1136. |
入库方式： OAI收割
来源：生态环境研究中心
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。