Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth
文献类型：期刊论文
| 作者 | Gan, Nanqin; Sun, Xiaoyun; Song, Lirong |
| 刊名 | CHEMICAL RESEARCH IN TOXICOLOGY
 |
| 出版日期 | 2010-09-01 |
| 卷号 | 23期号:9页码:1477-1484 |
| 关键词 | MITOCHONDRIAL PERMEABILITY TRANSITION TRANSCRIPTION FACTOR NRF2 OXIDATIVE STRESS LUNG-CANCER NAD(P)H-QUINONE OXIDOREDUCTASE INDUCED APOPTOSIS RAT HEPATOCYTES PROTECTION KEAP1 STABILIZATION |
| ISSN号 | 0893-228X |
| 通讯作者 | Song, LR, CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China |
| 中文摘要 | Microcystin-LR (MC-LR) is a potent heptapeptide hepatotoxin at high doses, but its underlying mechanism of promoting liver cell proliferation at low doses is unclear. The transcription factor nuclear factor erythroid 2-related factor 2 (Nr12) is key in mediating the protective antioxidant response against various environmental toxicants, but emerging data suggest that constitutive activation of Nrf2 contributes to a malignant phenotype. The purpose of this study was to characterize the interactions and effects of NrI2 activation on cell proliferation induced by MC-LR treatment. Treatment of HepG2 and Flep3B cells with MC-LR resulted in significant increases in Nrf2-ARE binding activities in the nuclear fractions and upregulation of its downstream genes HO-1 and NQO1. A possible mechanism may be that MC-LR binds to the cytosolic regulator protein Keap1 to liberate Nrf2. Nrf2 knockdown inhibited MC-LR-induced cell proliferation and cell cycle progression. Together, these results indicate that MC-LR-induced upregulation of Nrf2 in cancer cells promotes liver cancer cell growth and suggest a positive role of Nrf2 in tumorigenesis. |
| 英文摘要 | Microcystin-LR (MC-LR) is a potent heptapeptide hepatotoxin at high doses, but its underlying mechanism of promoting liver cell proliferation at low doses is unclear. The transcription factor nuclear factor erythroid 2-related factor 2 (Nr12) is key in mediating the protective antioxidant response against various environmental toxicants, but emerging data suggest that constitutive activation of Nrf2 contributes to a malignant phenotype. The purpose of this study was to characterize the interactions and effects of NrI2 activation on cell proliferation induced by MC-LR treatment. Treatment of HepG2 and Flep3B cells with MC-LR resulted in significant increases in Nrf2-ARE binding activities in the nuclear fractions and upregulation of its downstream genes HO-1 and NQO1. A possible mechanism may be that MC-LR binds to the cytosolic regulator protein Keap1 to liberate Nrf2. Nrf2 knockdown inhibited MC-LR-induced cell proliferation and cell cycle progression. Together, these results indicate that MC-LR-induced upregulation of Nrf2 in cancer cells promotes liver cancer cell growth and suggest a positive role of Nrf2 in tumorigenesis. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences |
| 学科主题 | Chemistry ; Medicinal; Chemistry ; Multidisciplinary; Toxicology |
| 类目[WOS] | Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology |
| 研究领域[WOS] | Pharmacology & Pharmacy ; Chemistry ; Toxicology |
| 关键词[WOS] | MITOCHONDRIAL PERMEABILITY TRANSITION ; TRANSCRIPTION FACTOR NRF2 ; OXIDATIVE STRESS ; LUNG-CANCER ; NAD(P)H-QUINONE OXIDOREDUCTASE ; INDUCED APOPTOSIS ; RAT HEPATOCYTES ; PROTECTION ; KEAP1 ; STABILIZATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000281840600006 |
| 公开日期 | 2010-12-23 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/13773]  |
| 专题 | 水生生物研究所_藻类生物学及应用研究中心_期刊论文 |
| 作者单位 | Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gan, Nanqin,Sun, Xiaoyun,Song, Lirong. Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2010,23(9):1477-1484. |
| APA | Gan, Nanqin,Sun, Xiaoyun,&Song, Lirong.(2010).Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth.CHEMICAL RESEARCH IN TOXICOLOGY,23(9),1477-1484. |
| MLA | Gan, Nanqin,et al."Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth".CHEMICAL RESEARCH IN TOXICOLOGY 23.9(2010):1477-1484. |
入库方式： OAI收割
来源：水生生物研究所
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