title: Microcystin-LR induced developmental toxicity and apoptosis in zebrafish (Danio rerio) larvae by activation of ER stress response.
abstract: Recent studies have demonstrated that cyanobacteria-derived Microcystin-LR (MC-LR) can cause developmental toxicity and trigger apoptosis in zebrafish (Danio rerio) larvae, but the underlying mechanisms remain largely unknown. In this study, we tested the hypothesis that the mechanism by which MC-LR induces developmental toxicity is through activation of endoplasmic reticulum (ER) stress. MC-LR (4.0 μM) exposure through submersion caused serious developmental toxicity, such as malformation, growth delay and decreased heart rates in zebrafish larvae, which could be inhibited by ER stress blocker, tauroursodeoxycholic acid (TUDCA, 20 μM). Meanwhile, acridine orange (AO) staining showed TUDCA could rescue cell apoptosis in heart area in zebrafish larvae resulted by MC-LR exposure. Real-time polymerase chain reaction (real-time PCR) analysis demonstrated that MC-LR induced activation of ER stress which consequently triggered apoptosis in zebrafish larvae. Protein expression examined by western blot indicated that MC-LR could activate MAPK8/Bcl-2/Bax pathway and caspase-dependent apoptotic pathway in zebrafish larva and the effects were mitigated by inhibition of ER stress. Taken together, the results observed in this study suggested that ER stress plays a critical role in developmental toxicity and apoptosis in zebrafish embryos exposed to MC-LR.
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Qi
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Dang
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Yu
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, China; Collaborative Innovation Center for Efficient and Health Production of Fisheries in Hunan Province, Changde 415000, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, China. Electronic address: whtjwjh@163.com.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D011897:Random Allocation; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D008387:Marine Toxins; D052998:Microcystins; D014874:Water Pollutants, Chemical; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C057862:cyanoginosin LR
keywords: Developmental toxicity; Endoplasmic reticulum; Microcystin; Stress; Zebrafish