title: Microcystin-LR induced reactive oxygen species mediate cytoskeletal disruption and apoptosis of hepatocytes in Cyprinus carpio L.
abstract: Microcystins (MCs) are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR) contains Leucine (L) and Arginine (R) in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A) activities and induce excessive production of reactive oxygen species (ROS). The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the hydroxyl radical (•OH) was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS) production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC) provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO) exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12-48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity.
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing, People's Republic of China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing, People's Republic of China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing, People's Republic of China.
authors.forename: Weili
authors.initials: W
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing, People's Republic of China.
authors.forename: Junying
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing, People's Republic of China.
authors.forename: Deyang
authors.initials: D
authors.lastname: Kong
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000633:toxicity; D002347:Carps / Q000378:metabolism* / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology*; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry; D008387:Marine Toxins; D052998:Microcystins / Q000378:metabolism / Q000633:toxicity*; D018613:Microscopy, Confocal; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D017931:DNA Primers; D008387:Marine Toxins; D052998:Microcystins; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; C057862:cyanoginosin LR