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题名: Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp (Aristich-thys nobilis)
作者: Li, Wei1; Chen, Jun1; Xie, Ping1; He, Jun1; Guo, Xiaochun1; Tuo, Xun1; Zhang, Wei1; Wu, Laiyan1
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 South Rd 7, Wuhan 430072, Peoples R China.
关键词: Biotransformation and detoxification ; mechanisms ; MC-RR-GSH/Cys ; GSH pathway ; Bighead carp
刊名: AQUATIC TOXICOLOGY
发表日期: 2014-02-01
DOI: 10.1016/j.aquatox.2013.12.001
卷: 147, 页:18-25
收录类别: SCI
文章类型: Article
部门归属: [Li, Wei ; Chen, Jun ; Xie, Ping ; He, Jun ; Guo, Xiaochun ; Tuo, Xun ; Zhang, Wei ; Wu, Laiyan] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Nature Science Foundations of China [31070457]
类目[WOS]: Marine & Freshwater Biology ; Toxicology
研究领域[WOS]: Marine & Freshwater Biology ; Toxicology
摘要: The glutathione and cysteine conjugates of microcystin (MC-GSH and MC-Cys, respectively) are two important metabolites in the detoxification of microcystins (MCs). Although studies have quantitated both conjugates, the reason why the amounts of MC-GSH are much lower than those of MC-Cys in various animal organs remains unknown. In this study, MC-RR-GSH and MC-RR-Cys were respectively i.p. injected into the cyanobacteria-eating bighead carp (Aristichthys nobilis), to explore the biotransformation and detoxification mechanisms of the two conjugates. The contents of MC-RR, MC-RR-GSH, MC-RR-Cys and MC-RR-N-acetyl-cysteine (MC-RR-Nac, the acetylation product of MC-RR-Cys) in the liver, kidney, intestine and blood of bighead carp in both groups were quantified via liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). In the MC-RR-GSH-treated group, the MC-RR-Cys content in the kidney increased 96.7-fold from 0.25 to 0.5 h post-injection, demonstrating that MC-RR-GSH acts as a highly reactive intermediate and is rapidly converted to MC-RR-Cys. The presence of MC-RR in both MC-RR-GSH- and MC-RR-Cys-treated groups indicates, for the first time, that MC conjugation with the thiol of GSH/Cys is a reversible process in vivo. Total MC-RR concentrations dissociated from MC-RR-Cys were lower than those from MC-RR-GSH, suggesting that MC-RR-Cys is more capable of detoxifying MC-RR. MC-RR-Cys was the most effectively excreted form in both the kidney and intestine, as the ratios of MC-RR-Cys to MC-RR reached as high as 15.2,2.9 in the MC-RR-GSH-treated group and 63.4, 19.1 in the MC-RR-Cys-treated group. Whereas MC-RR-Nac could not be found in all of the samples of the present study. Our results indicate that MC-RR-GSH was rapidly converted to MC-RR-Cys and then excreted, and that both glutathione and cysteine conjugates could release MC-RR. This study quantitatively proves the importance of the GSH detoxification pathway and furthers our understanding of the biochemical mechanism by which bighead carp are resistant to toxic cyanobacteria. (C) 2014 Elsevier B.V. All rights reserved.
英文摘要: The glutathione and cysteine conjugates of microcystin (MC-GSH and MC-Cys, respectively) are two important metabolites in the detoxification of microcystins (MCs). Although studies have quantitated both conjugates, the reason why the amounts of MC-GSH are much lower than those of MC-Cys in various animal organs remains unknown. In this study, MC-RR-GSH and MC-RR-Cys were respectively i.p. injected into the cyanobacteria-eating bighead carp (Aristichthys nobilis), to explore the biotransformation and detoxification mechanisms of the two conjugates. The contents of MC-RR, MC-RR-GSH, MC-RR-Cys and MC-RR-N-acetyl-cysteine (MC-RR-Nac, the acetylation product of MC-RR-Cys) in the liver, kidney, intestine and blood of bighead carp in both groups were quantified via liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). In the MC-RR-GSH-treated group, the MC-RR-Cys content in the kidney increased 96.7-fold from 0.25 to 0.5 h post-injection, demonstrating that MC-RR-GSH acts as a highly reactive intermediate and is rapidly converted to MC-RR-Cys. The presence of MC-RR in both MC-RR-GSH- and MC-RR-Cys-treated groups indicates, for the first time, that MC conjugation with the thiol of GSH/Cys is a reversible process in vivo. Total MC-RR concentrations dissociated from MC-RR-Cys were lower than those from MC-RR-GSH, suggesting that MC-RR-Cys is more capable of detoxifying MC-RR. MC-RR-Cys was the most effectively excreted form in both the kidney and intestine, as the ratios of MC-RR-Cys to MC-RR reached as high as 15.2,2.9 in the MC-RR-GSH-treated group and 63.4, 19.1 in the MC-RR-Cys-treated group. Whereas MC-RR-Nac could not be found in all of the samples of the present study. Our results indicate that MC-RR-GSH was rapidly converted to MC-RR-Cys and then excreted, and that both glutathione and cysteine conjugates could release MC-RR. This study quantitatively proves the importance of the GSH detoxification pathway and furthers our understanding of the biochemical mechanism by which bighead carp are resistant to toxic cyanobacteria. (C) 2014 Elsevier B.V. All rights reserved.
关键词[WOS]: ANION TRANSPORTING POLYPEPTIDES ; TANDEM MASS-SPECTROMETRY ; HEPATOTOXIC MICROCYSTINS ; FISH ; RAT ; IDENTIFICATION ; CYANOBACTERIA ; METABOLISM ; LIVER ; BIOACCUMULATION
语种: 英语
WOS记录号: WOS:000331856600003
ISSN号: 0166-445X
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20024
Appears in Collections:淡水生态学研究中心_期刊论文

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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

Recommended Citation:
Li, Wei; Chen, Jun; Xie, Ping; He, Jun; Guo, Xiaochun; Tuo, Xun; Zhang, Wei; Wu, Laiyan.Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp (Aristich-thys nobilis),AQUATIC TOXICOLOGY,2014,147():18-25
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