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Zebrafish Neurotoxicity from Aphantoxins-Cyanobacterial Paralytic Shellfish Poisons (PSPs) from Aphanizomenon flos-aquae DC-1
Zhang, Delu1,2,3; Hu, Chunxiang1; Wang, Gaohong1; Li, Dunhai1; Li, Genbao1; Liu, Yongding1; Liu, YD (reprint author), Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China.
2013-05-01
Source PublicationENVIRONMENTAL TOXICOLOGY
ISSN1520-4081
Volume28Issue:5Pages:239-254
AbstractAphanizomenon flos-aquae (A. flos-aquae), a cyanobacterium frequently encountered in water blooms worldwide, is source of neurotoxins known as PSPs or aphantoxins that present a major threat to the environment and to human health. Although the molecular mechanism of PSP action is well known, many unresolved questions remain concerning its mechanisms of toxicity. Aphantoxins purified from a natural isolate of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography (HPLC), the major component toxins were the gonyautoxins1 and 5 (GTX1 and GTX5, 34.04% and 21.28%, respectively) and the neosaxitoxin (neoSTX, 12.77%). The LD50 of the aphantoxin preparation was determined to be 11.33 mu g/kg (7.75 mu g saxitoxin equivalents (STXeq) per kg) following intraperitoneal injection of zebrafish (Danio rerio). To address the neurotoxicology of the aphantoxin preparation, zebrafish were injected with low and high sublethal doses of A. flos-aquae DC-1 toxins 7.73 and 9.28 mu g /kg (5.3 and 6.4 mu g STXeq/kg, respectively) and brain tissues were analyzed by electron microscopy and RT-PCR at different timepoints postinjection. Low-dose aphantoxin exposure was associated with chromatin condensation, cell-membrane blebbing, and the appearance of apoptotic bodies. High-dose exposure was associated with cytoplasmic vacuolization, mitochondrial swelling, and expansion of the endoplasmic reticulum. At early timepoints (3 h) many cells exhibited characteristic features of both apoptosis and necrosis. At later timepoints apoptosis appeared to predominate in the low-dose group, whereas necrosis predominated in the high-dose group. RT-PCR revealed that mRNA levels of the apoptosis-related genes encoding p53, Bax, caspase-3, and c-Jun were upregulated after aphantoxin exposure, but there was no evidence of DNA laddering; apoptosis could take place by pathways independent of DNA fragmentation. These results demonstrate that aphantoxin exposure can cause cell death in zebrafish brain tissue, with low doses inducing apoptosis and higher doses inducing necrosis. (C) 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 239-254, 2013.; Aphanizomenon flos-aquae (A. flos-aquae), a cyanobacterium frequently encountered in water blooms worldwide, is source of neurotoxins known as PSPs or aphantoxins that present a major threat to the environment and to human health. Although the molecular mechanism of PSP action is well known, many unresolved questions remain concerning its mechanisms of toxicity. Aphantoxins purified from a natural isolate of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography (HPLC), the major component toxins were the gonyautoxins1 and 5 (GTX1 and GTX5, 34.04% and 21.28%, respectively) and the neosaxitoxin (neoSTX, 12.77%). The LD50 of the aphantoxin preparation was determined to be 11.33 mu g/kg (7.75 mu g saxitoxin equivalents (STXeq) per kg) following intraperitoneal injection of zebrafish (Danio rerio). To address the neurotoxicology of the aphantoxin preparation, zebrafish were injected with low and high sublethal doses of A. flos-aquae DC-1 toxins 7.73 and 9.28 mu g /kg (5.3 and 6.4 mu g STXeq/kg, respectively) and brain tissues were analyzed by electron microscopy and RT-PCR at different timepoints postinjection. Low-dose aphantoxin exposure was associated with chromatin condensation, cell-membrane blebbing, and the appearance of apoptotic bodies. High-dose exposure was associated with cytoplasmic vacuolization, mitochondrial swelling, and expansion of the endoplasmic reticulum. At early timepoints (3 h) many cells exhibited characteristic features of both apoptosis and necrosis. At later timepoints apoptosis appeared to predominate in the low-dose group, whereas necrosis predominated in the high-dose group. RT-PCR revealed that mRNA levels of the apoptosis-related genes encoding p53, Bax, caspase-3, and c-Jun were upregulated after aphantoxin exposure, but there was no evidence of DNA laddering; apoptosis could take place by pathways independent of DNA fragmentation. These results demonstrate that aphantoxin exposure can cause cell death in zebrafish brain tissue, with low doses inducing apoptosis and higher doses inducing necrosis. (C) 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 239-254, 2013.
SubtypeArticle
KeywordAphantoxin Apoptosis Brain Dna Damage Ultrastructure Zebrafish
Department[Zhang, Delu ; Hu, Chunxiang ; Wang, Gaohong ; Li, Dunhai ; Li, Genbao ; Liu, Yongding] Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China ; [Zhang, Delu] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China ; [Zhang, Delu] Wuhan Univ Technol, Dept Biol, Wuhan 430070, Peoples R China
DOI10.1002/tox.20714
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
Funding OrganizationNational Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007] ; National Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007] ; National Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007] ; National Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007]
Indexed BySCI
Language英语
WOS Research AreaEnvironmental Sciences & Ecology ; Toxicology ; Water Resources
WOS SubjectEnvironmental Sciences ; Toxicology ; Water Resources
WOS IDWOS:000318576200001
WOS KeywordCASPASE-ACTIVATED DNASE ; ALKALINE-PHOSPHATASE ACTIVITIES ; ISCHEMIA-REPERFUSION INJURY ; IMMEDIATE-EARLY GENES ; FISH OREOCHROMIS-SP. ; AMYLOID-BETA-PEPTIDE ; C-JUN ; CELL-DEATH ; SODIUM-CHANNELS ; PATHOLOGICAL-CHANGES
Funding OrganizationNational Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007] ; National Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007] ; National Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007] ; National Basic Research Programs of China [2008CB418002., 2008CB418001]; National Principal Expert Program on treatment and control of water pollution [2009ZX07106-001, 2008ZX07103-004, 2008ZX07103-007]
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Cited Times:18[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19323
Collection水环境工程研究中心_期刊论文
Corresponding AuthorLiu, YD (reprint author), Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China.
Affiliation1.Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China
3.Wuhan Univ Technol, Dept Biol, Wuhan 430070, Peoples R China
Recommended Citation
GB/T 7714
Zhang, Delu,Hu, Chunxiang,Wang, Gaohong,et al. Zebrafish Neurotoxicity from Aphantoxins-Cyanobacterial Paralytic Shellfish Poisons (PSPs) from Aphanizomenon flos-aquae DC-1[J]. ENVIRONMENTAL TOXICOLOGY,2013,28(5):239-254.
APA Zhang, Delu.,Hu, Chunxiang.,Wang, Gaohong.,Li, Dunhai.,Li, Genbao.,...&Liu, YD .(2013).Zebrafish Neurotoxicity from Aphantoxins-Cyanobacterial Paralytic Shellfish Poisons (PSPs) from Aphanizomenon flos-aquae DC-1.ENVIRONMENTAL TOXICOLOGY,28(5),239-254.
MLA Zhang, Delu,et al."Zebrafish Neurotoxicity from Aphantoxins-Cyanobacterial Paralytic Shellfish Poisons (PSPs) from Aphanizomenon flos-aquae DC-1".ENVIRONMENTAL TOXICOLOGY 28.5(2013):239-254.
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