PMID- 27219292 OWN - NLM STAT- MEDLINE DCOM- 20170221 LR - 20201209 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 157 DP - 2016 Aug TI - Microcystin-LR induced developmental toxicity and apoptosis in zebrafish (Danio rerio) larvae by activation of ER stress response. PG - 166-73 LID - S0045-6535(16)30678-6 [pii] LID - 10.1016/j.chemosphere.2016.05.038 [doi] AB - 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 muM) 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 muM). 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. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Qi, Mei AU - Qi M AD - College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China. FAU - Dang, Yao AU - Dang Y AD - College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China. FAU - Xu, Qinglong AU - Xu Q AD - College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China. FAU - Yu, Liqin AU - Yu L AD - College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, China. FAU - Liu, Chunsheng AU - Liu C AD - 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. FAU - Yuan, Yongchao AU - Yuan Y AD - College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China. FAU - Wang, Jianghua AU - Wang J AD - College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, China. Electronic address: whtjwjh@163.com. LA - eng PT - Journal Article DEP - 20160521 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (Bacterial Toxins) RN - 0 (Marine Toxins) RN - 0 (Microcystins) RN - 0 (Water Pollutants, Chemical) RN - 516-35-8 (Taurochenodeoxycholic Acid) RN - 60EUX8MN5X (ursodoxicoltaurine) RN - EQ8332842Y (cyanoginosin LR) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Bacterial Toxins/toxicity MH - Dose-Response Relationship, Drug MH - Endoplasmic Reticulum Stress/*drug effects MH - Marine Toxins MH - Microcystins/*toxicity MH - Random Allocation MH - Taurochenodeoxycholic Acid/*pharmacology MH - Water Pollutants, Chemical/*toxicity MH - Zebrafish/growth & development/*metabolism OTO - NOTNLM OT - Developmental toxicity OT - Endoplasmic reticulum OT - Microcystin OT - Stress OT - Zebrafish EDAT- 2016/05/25 06:00 MHDA- 2017/02/22 06:00 CRDT- 2016/05/25 06:00 PHST- 2016/03/29 00:00 [received] PHST- 2016/05/12 00:00 [revised] PHST- 2016/05/12 00:00 [accepted] PHST- 2016/05/25 06:00 [entrez] PHST- 2016/05/25 06:00 [pubmed] PHST- 2017/02/22 06:00 [medline] AID - S0045-6535(16)30678-6 [pii] AID - 10.1016/j.chemosphere.2016.05.038 [doi] PST - ppublish SO - Chemosphere. 2016 Aug;157:166-73. doi: 10.1016/j.chemosphere.2016.05.038. Epub 2016 May 21.