Proteasome Inhibitors Activate Autophagy Involving Inhibition of PI3K-Akt-mTOR Pathway as an Anti-Oxidation Defense in Human RPE Cells
文献类型：期刊论文
| 作者 | Tang, BR; Cai, JJ; Sun, L; Li, YP; Qu, J; Snider, BJ; Wu, SZ |
| 刊名 | PLOS ONE
 |
| 出版日期 | 2014 |
| 卷号 | 9期号:7页码:e103364-e103364 |
| 通讯作者 | Wu, SZ (reprint author), Wenzhou Med Univ, Sch Optometry & Ophthalmol, Wenzhou, Zhejiang, Peoples R China.,wszlab@mail.eye.ac.cn |
| 英文摘要 | The two major intracellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, work collaboratively in many biological processes including development, apoptosis, aging, and countering oxidative injuries. We report here that, in human retinal pigment epithelial cells (RPE), ARPE-19 cells, proteasome inhibitors, clasto-lactacystin beta-lactone (LA) or epoxomicin (Epo), at non-lethal doses, increased the protein levels of autophagy-specific genes Atg5 and Atg7 and enhanced the conversion of microtubule-associated protein light chain (LC3) from LC3-I to its lipidative form, LC3-II, which was enhanced by co-addition of the saturated concentration of Bafilomycin A1 (Baf). Detection of co-localization for LC3 staining and labeled-lysosome further confirmed autophagic flux induced by LA or Epo. LA or Epo reduced the phosphorylation of the protein kinase B (Akt), a downstream target of phosphatidylinositol-3-kinases (PI3K), and mammalian target of rapamycin (mTOR) in ARPE-19 cells; by contrast, the induced changes of autophagy substrate, p62, showed biphasic pattern. The autophagy inhibitor, Baf, attenuated the reduction in oxidative injury conferred by treatment with low doses of LA and Epo in ARPE-19 cells exposed to menadione (VK3) or 4-hydroxynonenal (4-HNE). Knockdown of Atg7 with siRNA in ARPE-19 cells reduced the protective effects of LA or Epo against VK3. Overall, our results suggest that treatment with low levels of proteasome inhibitors confers resistance to oxidative injury by a pathway involving inhibition of the PI3K-Akt-mTOR pathway and activation of autophagy. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 关键词[WOS] | ENDOPLASMIC-RETICULUM STRESS ; MACULAR DEGENERATION ; OXIDATIVE STRESS ; CANCER CELLS ; RCS RAT ; DEATH ; DEGRADATION ; P62/SQSTM1 ; EXPRESSION ; LIPOFUSCIN |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000339992600063 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/208]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Tang, BR,Cai, JJ,Sun, L,et al. Proteasome Inhibitors Activate Autophagy Involving Inhibition of PI3K-Akt-mTOR Pathway as an Anti-Oxidation Defense in Human RPE Cells[J]. PLOS ONE,2014,9(7):e103364-e103364. |
| APA | Tang, BR.,Cai, JJ.,Sun, L.,Li, YP.,Qu, J.,...&Wu, SZ.(2014).Proteasome Inhibitors Activate Autophagy Involving Inhibition of PI3K-Akt-mTOR Pathway as an Anti-Oxidation Defense in Human RPE Cells.PLOS ONE,9(7),e103364-e103364. |
| MLA | Tang, BR,et al."Proteasome Inhibitors Activate Autophagy Involving Inhibition of PI3K-Akt-mTOR Pathway as an Anti-Oxidation Defense in Human RPE Cells".PLOS ONE 9.7(2014):e103364-e103364. |
入库方式： OAI收割
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。