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学科主题: Pharmacology & Pharmacy; Toxicology
题名: Sulforaphane protects Microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response
作者: Gan, Nanqin1; Mi, Lixin2; Sun, Xiaoyun1; Dai, Guofei1; Chung, Fung-Lung2; Song, Lirong1
通讯作者: Song, LR, CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Beijing, Peoples R China
关键词: Microcystin-LR (MC-LR) ; Sulforaphane (SFN) ; NF-E2-related factor 2 (Nrf2) ; Phase II enzymes ; Glutathione (GSH) ; Chemoprevention
刊名: TOXICOLOGY AND APPLIED PHARMACOLOGY
发表日期: 2010-09-01
DOI: 10.1016/j.taap.2010.06.005
卷: 247, 期:2, 页:129-137
收录类别: SCI
文章类型: Article
部门归属: [Gan, Nanqin; Sun, Xiaoyun; Dai, Guofei; Song, Lirong] CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Beijing, Peoples R China; [Mi, Lixin; Chung, Fung-Lung] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: 973 program [2008CB418000]; Natural Science Foundation of China [U0833604]; Chinese Academy of Sciences [KZCX1-YW-14-1]; National water pollution control and management technology [2009ZX07527-005]
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
摘要: Microcystins (MCs), a cyclic heptapeptide hepatotoxins. are mainly produced by the bloom-forming cyanobacerium Microcystis, which has become an environmental hazard worldwide. Long term consumption of MC-contaminated water may induce liver damage, liver cancer, and even human death. Therefore, in addition to removal of MCs in drinking water, novel strategies that prevent health damages are urgently needed. Sulforaphane (SFN), a natural-occurring isothiocyanate from cruciferous vegetables, has been reported to reduce and eliminate toxicities from xenobiotics and carcinogens. The purpose of the present study was to provide mechanistic insights into the SFN-induced antioxidative defense system against MC-LR-induced cytotoxicity. We performed cell viability assays, including MTS assay, colony formation assay and apoptotic cell sorting, to study MC-LR-induced cellular damage and the protective effects by SFN. The results showed that SFN protected MC-LR-induced damages at a nontoxic and physiological relevant dose in HepG2, BRL-3A and NIH 3 T3 cells. The protection was Nrf2-mediated as evident by transactivation of Nrf2 and activation of its downstream genes, including NQO1 and HO-1, and elevated intracellular GSH level. Results of our studies indicate that pretreatment of cells with 10 mu M SFN for 12 h significantly protected cells from MC-LR-induced damage. SFN-induced protective response was mediated through Nrf2 pathway. (C) 2010 Elsevier Inc. All rights reserved.
英文摘要: Microcystins (MCs), a cyclic heptapeptide hepatotoxins. are mainly produced by the bloom-forming cyanobacerium Microcystis, which has become an environmental hazard worldwide. Long term consumption of MC-contaminated water may induce liver damage, liver cancer, and even human death. Therefore, in addition to removal of MCs in drinking water, novel strategies that prevent health damages are urgently needed. Sulforaphane (SFN), a natural-occurring isothiocyanate from cruciferous vegetables, has been reported to reduce and eliminate toxicities from xenobiotics and carcinogens. The purpose of the present study was to provide mechanistic insights into the SFN-induced antioxidative defense system against MC-LR-induced cytotoxicity. We performed cell viability assays, including MTS assay, colony formation assay and apoptotic cell sorting, to study MC-LR-induced cellular damage and the protective effects by SFN. The results showed that SFN protected MC-LR-induced damages at a nontoxic and physiological relevant dose in HepG2, BRL-3A and NIH 3 T3 cells. The protection was Nrf2-mediated as evident by transactivation of Nrf2 and activation of its downstream genes, including NQO1 and HO-1, and elevated intracellular GSH level. Results of our studies indicate that pretreatment of cells with 10 mu M SFN for 12 h significantly protected cells from MC-LR-induced damage. SFN-induced protective response was mediated through Nrf2 pathway. (C) 2010 Elsevier Inc. All rights reserved.
关键词[WOS]: GLUTATHIONE S-TRANSFERASES ; PHASE-2 ENZYMES ; GENE-EXPRESSION ; CANCER RISK ; NRF2 ; MICE ; INDUCTION ; PATHWAY ; CELLS ; KEAP1
语种: 英语
WOS记录号: WOS:000280903000008
ISSN号: 0041-008X
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/13779
Appears in Collections:藻类生物学及应用研究中心_期刊论文

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作者单位: 1.CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Beijing, Peoples R China
2.Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA

Recommended Citation:
Gan, Nanqin; Mi, Lixin; Sun, Xiaoyun; Dai, Guofei; Chung, Fung-Lung; Song, Lirong.Sulforaphane protects Microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response,TOXICOLOGY AND APPLIED PHARMACOLOGY,2010,247(2):129-137
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