Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study
文献类型：期刊论文
| 作者 | He, Jun1; Chen, Jun1; Wu, Laiyan1,2; Li, Guangyu1,3; Xie, Ping1 |
| 刊名 | JOURNAL OF PROTEOME RESEARCH
 |
| 出版日期 | 2012-12-01 |
| 卷号 | 11期号:12页码:5934-5946 |
| 关键词 | microcystin-LR metabonomics NMR glutathione choline nutrient absorption |
| ISSN号 | 1535-3893 |
| 通讯作者 | Chen, J (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Donghu S Rd 7, Wuhan 430072, Peoples R China. |
| 中文摘要 | Microcystin-LR (MCLR), a potent hepatotoxin, is causing increased risks to public health. Although the liver is the main target organ of MCLR, the metabolic profiling of liver in response to MCLR in vivo remains unknown. Here, we comprehensively analyzed the metabolic change of liver and ileal flushes in rat orally gavaged with MCLR by H-1 nuclear magnetic resonance (NMR). Quantification of hepatic MCLR and its glutathione and cysteine conjugates by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was conducted. Metabonomics results revealed significant associations of MCLR-induced disruption of hepatic metabolisms with inhibition of nutrient absorption, as evidenced by a severe decrease of 12 amino acids in the liver and their corresponding elevation in ileal flushes. The hepatic metabolism signature of MCLR was characterized by significant inhibition of tyrosine anabolism and catabolism, three disrupted pathways of choline metabolism, glutathione exhaustion, and disturbed nucleotide synthesis. Notably, substantial alterations of hepatic metabolism were observable even at the low MCLR-treated group (0.04 mg/kg MCLR), although no apparent histological changes in liver were observed in the low- and medium-dosed groups. These observations offered novel insights into the microcystin hepatotoxic mechanism at a functional level, thereby facilitating further assessment and clarification of human health risk from MCs exposure. |
| 英文摘要 | Microcystin-LR (MCLR), a potent hepatotoxin, is causing increased risks to public health. Although the liver is the main target organ of MCLR, the metabolic profiling of liver in response to MCLR in vivo remains unknown. Here, we comprehensively analyzed the metabolic change of liver and ileal flushes in rat orally gavaged with MCLR by H-1 nuclear magnetic resonance (NMR). Quantification of hepatic MCLR and its glutathione and cysteine conjugates by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was conducted. Metabonomics results revealed significant associations of MCLR-induced disruption of hepatic metabolisms with inhibition of nutrient absorption, as evidenced by a severe decrease of 12 amino acids in the liver and their corresponding elevation in ileal flushes. The hepatic metabolism signature of MCLR was characterized by significant inhibition of tyrosine anabolism and catabolism, three disrupted pathways of choline metabolism, glutathione exhaustion, and disturbed nucleotide synthesis. Notably, substantial alterations of hepatic metabolism were observable even at the low MCLR-treated group (0.04 mg/kg MCLR), although no apparent histological changes in liver were observed in the low- and medium-dosed groups. These observations offered novel insights into the microcystin hepatotoxic mechanism at a functional level, thereby facilitating further assessment and clarification of human health risk from MCs exposure. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Biochemical Research Methods |
| 研究领域[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | TYPE-2A PROTEIN PHOSPHATASES ; GENE-EXPRESSION CHANGES ; HEPATOTOXIC MICROCYSTINS ; CARDIOVASCULAR-DISEASE ; GLUTATHIONE CONJUGATE ; QUANTITATIVE-ANALYSIS ; MOLECULAR-MECHANISMS ; INHIBITORY-ACTIVITY ; DNA METHYLATION ; BIGHEAD CARP |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China [31070457] |
| 语种 | 英语 |
| WOS记录号 | WOS:000311925900033 |
| 公开日期 | 2013-10-31 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/19301]  |
| 专题 | 水生生物研究所_淡水生态学研究中心_期刊论文 |
| 作者单位 | 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China 2.S Cent Univ Nationalities, Coll Chem & Mat Sci, Wuhan 430074, Peoples R China 3.Huazhong Agr Univ, Coll Fisheries, Wuhan, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Jun,Chen, Jun,Wu, Laiyan,et al. Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study[J]. JOURNAL OF PROTEOME RESEARCH,2012,11(12):5934-5946. |
| APA | He, Jun,Chen, Jun,Wu, Laiyan,Li, Guangyu,&Xie, Ping.(2012).Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study.JOURNAL OF PROTEOME RESEARCH,11(12),5934-5946. |
| MLA | He, Jun,et al."Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study".JOURNAL OF PROTEOME RESEARCH 11.12(2012):5934-5946. |
入库方式： OAI收割
来源：水生生物研究所
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