title: The organic anion transporting polypeptide 1a5 is a pivotal transporter for the uptake of microcystin-LR by gonadotropin-releasing hormone neurons.
abstract: Microcystins (MCs) are widely distributed hepatotoxic polypeptides produced by cyanobacteria. Microcystin-LR (MC-LR) has the broadest distribution and strongest toxicity among more than 80 isoforms of hepatotoxic MCs. MC-LR suppresses the expression of gonadotropin-releasing hormone (GnRH) that is critically required for the release of testosterone, resulting in the induction of male reproductive toxicity. However, the specific mechanisms of the uptake of MC-LR by GnRH-secreting neurons still remain unclear. In this study, GT1-7 cells were exposed to MC-LR in order to determine whether the GnRH-secreting neurons were the target of MC-LR that could induce male reproductive toxicity. Our data demonstrated that at least four organic anion transporting polypeptides (Oatp1a4, Oatp1a5, Oatp5a1, Oatp2b1) were expressed in GnRH neurons at the mRNA level, but only Oatp1a5 was expressed at the protein level. Furthermore, we demonstrated that MC-LR could not be transported into Oatp1a5-deficient GT1-7 cells which were protected from cell viability loss induced by MC-LR. These data suggest that Oatp1a5 may play an important role in the toxic effect of MC-LR on GnRH neurons.
authors.affiliation: Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China. Electronic address: djie@nju.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China. Electronic address: 1543793201@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China Mailing address: Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Hankou Road 22, Nanjing 210093, China. Electronic address: zou.xiang@gu.se.
authors.forename: Zou
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China. Electronic address: 1160834412@qq.com.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Diao
authors.affiliation: Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China. Electronic address: 499180109@qq.com.
authors.forename: Moxi
authors.initials: M
authors.lastname: Su
authors.affiliation: Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China. Electronic address: 1490220368@qq.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China. Electronic address: 1483179828@qq.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Wan
authors.affiliation: Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China. Electronic address: hanxd@nju.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000458:Cyanobacteria / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D008387:Marine Toxins; D052998:Microcystins / Q000378:metabolism* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D012098:Reproduction / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D027361:Organic Anion Transporters; D014874:Water Pollutants, Chemical; D007987:Gonadotropin-Releasing Hormone; C057862:cyanoginosin LR
keywords: Cyanobacteria; Gonadotropin-releasing hormone; Male reproductive toxicity; Microcystin-LR; Organic anion transporting polypeptides; Water contamination