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Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp (Aristich-thys nobilis)
Li, Wei; Chen, Jun; Xie, Ping; He, Jun; Guo, Xiaochun; Tuo, Xun; Zhang, Wei; Wu, Laiyan; 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.
2014-02-01
Source PublicationAQUATIC TOXICOLOGY
ISSN0166-445X
Volume147Pages:18-25
AbstractThe 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.; 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.
SubtypeArticle
KeywordBiotransformation And Detoxification Mechanisms Mc-rr-gsh/cys Gsh Pathway Bighead Carp
Department[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
DOI10.1016/j.aquatox.2013.12.001
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Nature Science Foundations of China [31070457] ; National Nature Science Foundations of China [31070457] ; National Nature Science Foundations of China [31070457] ; National Nature Science Foundations of China [31070457]
Indexed BySCI
Language英语
WOS Research AreaMarine & Freshwater Biology ; Toxicology
WOS SubjectMarine & Freshwater Biology ; Toxicology
WOS IDWOS:000331856600003
WOS KeywordANION TRANSPORTING POLYPEPTIDES ; TANDEM MASS-SPECTROMETRY ; HEPATOTOXIC MICROCYSTINS ; FISH ; RAT ; IDENTIFICATION ; CYANOBACTERIA ; METABOLISM ; LIVER ; BIOACCUMULATION
Funding OrganizationNational Nature Science Foundations of China [31070457] ; National Nature Science Foundations of China [31070457] ; National Nature Science Foundations of China [31070457] ; National Nature Science Foundations of China [31070457]
Citation statistics
Cited Times:22[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/20024
Collection淡水生态学研究中心_期刊论文
Corresponding AuthorChen, 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.
AffiliationChinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China
Recommended Citation
GB/T 7714
Li, Wei,Chen, Jun,Xie, Ping,et al. Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp (Aristich-thys nobilis)[J]. AQUATIC TOXICOLOGY,2014,147:18-25.
APA Li, Wei.,Chen, Jun.,Xie, Ping.,He, Jun.,Guo, Xiaochun.,...&Chen, J .(2014).Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp (Aristich-thys nobilis).AQUATIC TOXICOLOGY,147,18-25.
MLA Li, Wei,et al."Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp (Aristich-thys nobilis)".AQUATIC TOXICOLOGY 147(2014):18-25.
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