Genotoxicity of microcystin-LR in mammalian cells: Implication from peroxynitrite produced by mitochondria

doi:10.1016/j.ecoenv.2020.110408

	Genotoxicity of microcystin-LR in mammalian cells: Implication from peroxynitrite produced by mitochondria
	Wang, Xiaofei 1,2; Li, Yintao 2; Xiao, Hourong 2; Zhang, Min 2; Bao, Teng 2; Luo, Xun 3; Chen, Shaopeng 1
刊名	ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
	2020-06-01
卷号	195
关键词	Microcystin-LR DNA damage Peroxynitrite Mitochondria
ISSN号	0147-6513
DOI	10.1016/j.ecoenv.2020.110408
通讯作者	Wang, Xiaofei(wxf1985@mail.ustc.edu.cn) ; Chen, Shaopeng(spchen035@ipp.ac.cn)
英文摘要	Microcystin-LR (MC-LR) is a widely known hepatotoxin which could induce the occurrence and metastasis of hepatocellular carcinoma. In recent years, with the frequent outbreak of cyanobacteria, the harm of MC-LR has gradually attracted more attention. Hence, this study focused on the effect of MC-LR on DNA damage in HepG2 cells, identifying the types and sources of free radicals that make an important function on this issue. Our data suggested that MC-LR induced concentration- and time-dependent increasement of DNA double-strand breaks (DSBs). After exposure to 1 mu M MC-LR for 3 days, the protein expression and immunofluorescence staining of gamma-H2AX was significantly increased. Using a scavenger of mitochondrial O-2(center dot-)(4-hydroxy-tempo), a inhibitor of mitochondrial NOS (7-nitroindazole), and a scavenger of ONOO- (uric acid), it was revealed that ONOO- originated from mitochondria made a significant contribution to the genotoxicity of MC-LR. Moreover, a significant decreasement of mitochondrial membrane potential (MMP) was observed. These findings suggested that peroxynitrite targeting mitochondria plays a vital role in the MC-LR-induced genotoxic response in mammalian cells.
资助项目	Natural Science Foundation of Anhui Province[1808085QB37] ; Opening Foundation of Anhui Province of Key Laboratory of Environmental Toxicology and Pollution Control Technology[Y79AH72588-02] ; Talent Research Foundation of Hefei University[16-17RC03] ; Key Project of Natural Science Research of Anhui High Education Institutions[KJ 2018A0561] ; Key Project of Natural Science Research of Anhui High Education Institutions[KJ20180471] ; Major Project of Research Foundation of Hefei University[17ZR08ZDA]
WOS关键词	OXIDATIVE STRESS ; CHRONIC EXPOSURE ; HISTONE H2AX ; NITRIC-OXIDE ; HEPG2 CELLS ; DNA-DAMAGE ; CYTOTOXICITY ; DYSFUNCTION ; APOPTOSIS ; LIVER
WOS研究方向	Environmental Sciences & Ecology ; Toxicology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000525762800024
资助机构	Natural Science Foundation of Anhui Province ; Opening Foundation of Anhui Province of Key Laboratory of Environmental Toxicology and Pollution Control Technology ; Talent Research Foundation of Hefei University ; Key Project of Natural Science Research of Anhui High Education Institutions ; Major Project of Research Foundation of Hefei University
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103665]
专题	中国科学院合肥物质科学研究院
通讯作者	Wang, Xiaofei; Chen, Shaopeng
作者单位	1.Chinese Acad Sci, Hefei Inst Phys Sci, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, Hefei 230031, Peoples R China 2.Hefei Univ, Sch Biol Food & Environm, Hefei 230601, Peoples R China 3.Huainan Normal Univ, Sch Biol Engn, Huainan 232001, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xiaofei,Li, Yintao,Xiao, Hourong,et al. Genotoxicity of microcystin-LR in mammalian cells: Implication from peroxynitrite produced by mitochondria[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2020,195.
APA	Wang, Xiaofei.,Li, Yintao.,Xiao, Hourong.,Zhang, Min.,Bao, Teng.,...&Chen, Shaopeng.(2020).Genotoxicity of microcystin-LR in mammalian cells: Implication from peroxynitrite produced by mitochondria.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,195.
MLA	Wang, Xiaofei,et al."Genotoxicity of microcystin-LR in mammalian cells: Implication from peroxynitrite produced by mitochondria".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 195(2020).